curcumin and Kidney-Diseases

The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies.. This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans.. Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis.. This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.

Topics: Antioxidants; Berberine; Beta vulgaris; Betalains; Biological Products; Catechin; Curcumin; Disulfides; Flavonoids; Humans; Isothiocyanates; Kidney; Kidney Diseases; Plant Extracts; Pomegranate; Protective Agents; Resveratrol; Sulfinic Acids; Sulfoxides; Xanthophylls

Renal ischemia-reperfusion injury (RIRI) refers to a phenomenon associated with dysfunction of the kidney and tissue damage. Unfortunately, no specific drugs have been found that effectively prevent and treat RIRI. Curcumin (Cur), a polyphenol extracted from turmeric, possesses a variety of biological activities involving antioxidation, inhibition of apoptosis, inhibition of inflammation, and reduction of lipid peroxidation. Eight frequently used databases were searched using prespecified search strategies. The CAMARADES 10-item quality checklist was used to evaluate the risk of bias of included studies, and the RevMan 5.3 software was used to analyze the data. The risk of bias score of included studies ranged from 3 to 6 with an average score of 5.22. Compared with the control group, Cur significantly alleviated renal pathology, reduced blood urea nitrogen and serum creatinine levels, and improved inflammatory indexes, oxidant, and apoptosis in RIRI animal models. Despite the heterogeneity of the response to Cur in terms of serum creatinine, BUN, TNF-alpha, and SOD, its effectiveness for improving the injury of RIRI was remarkable. In the mouse model subgroup of serum creatinine, the effect size of the method of unilateral renal artery ligation with contralateral nephrectomy and shorter ischemic time showed a greater effect than that of the control group. No difference was seen in the methods of model establishment, mode administration, or medication times. The preclinical systematic review provided preliminary evidence that Cur partially improved RIRI in animal models, probably via anti-inflammatory, antioxidant, antiapoptosis, and antifibrosis activities and via improving microperfusion. ARRIVE guidelines are recommended; blinding and sample size calculation should be focused on in future studies. These data suggest that Cur is a potential renoprotective candidate for further clinical trials of RIRI.

Topics: Animals; Curcumin; Disease Models, Animal; Drug Evaluation, Preclinical; Kidney Diseases; Reperfusion Injury

Curcumin is the one of the main phenolic ingredients in curcuma species rhizome. Curcuma species have traditionally been used for the treatment of diabetes, cardiovascular, and renal diseases.. The present study was designed to review the scientific literature on the protective effects of curcumin against nephrotoxic agents.. Studies have shown the protective effects of curcumin against nephrotoxic agents such as gallic acid, glucose, tartrazine, streptozotocin, lead, cadmium, fluoride, maleate, malathion, nicotine, cisplatin, gentamicin, and methotrexate. However, further investigations are needed to determine the efficacy of curcumin as an antidote agent due to the lack of clinical trial studies. Therefore, it is recommended to conduct clinical trials in humans to confirm these effects.. The current review indicated that curcumin may be effective against nephrotoxicity by modulating oxidative stress and inflammatory responses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Humans; Kidney Diseases; Oxidative Stress; Protective Agents

Curcumin (U1) has a wide spectrum of therapeutic effects such as antitumor and anti-inflammatory effects, including antibacterial, antiviral, antifungal, and antispasmodic activities. By comparison of the structure-activity relationship, tetrahydrocurcumin (THU1), one of the major metabolites, showed the highest antioxidative activity in both in vitro and in vivo systems. U1 has been reported to have the nephroprotective effect to improve creatinine and urea clearance and also protected the chronic renal allograft nephropathy. These beneficial effects have been explained by the protection of oxidative stress and the induction of antioxidative enzymes. The protective effect of THU1 against ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage using male ddY mice was greater than that of U1, by monitoring not only radical scavenging activity measured by ESR, and TBARS, 4-HNE-modified protein and 8-OHdG formation but also induction of anioxidative enzymes and detoxification enzymes. THU1 was also expected to improve redox regulation through glutathione and suppress the oxidative stress in diabetic nephropathy and neuropathy. Earlier studies reported that U1 reduced the iron-induced hepatic damage, aflatoxin- and benzo[a]pyrene- induced mutagenicity and hepatocarcinogenecity and also the formation of the DNA adduct by inhibiting cytochrome P450 in the liver. The hepatoprotective role of U1 has been examined using carbone terachloride-induced liver damage in rats and alcoholic liver disease model rats, but not examined using THU1. Our recent data suggests that THU1 is a more promising hepatprotective agent because of its strong induction activity of antioxidant and phase 2-metabolizing enzymes in liver compared to kidney, although more detaied examinations are required.

Topics: Animals; Curcumin; Kidney; Kidney Diseases; Liver; Liver Diseases

Curcumin is turmeric extract that have antiproliferative, anti-cancer, and anti-oxidant effects and has been shown that it may have reno-protective properties. This study conducted to evaluate the efficacy of curcumin in the prevention of CIN.. This randomized placebo-controlled clinical trial was carried out on 138 patients with chronic stable angina scheduled for elective coronary angiography that had renal insufficiency. Patients were randomized to receive curcumin or placebo in addition to standard hydration with saline 0.9% before nonionic iso-osmolar contrast agent administration for angiography. Serum creatinine was measured 12h before, 24h and 48h after contrast injection. CIN, mainly, defined as increase in creatinine of ≥ 0.5 mg/dL or ≥ 25% from the baseline.. Serum creatinine change was 0.19 ± 0.31 mg/dL which was 0.22 ± 0.33 and 0.16 ± 0.29 in placebo and curcumin group, respectively. In 'repeated measure analysis' no statistically difference was found in serum creatinine level between pre-intervention, and 24 hours and 48 hours after intervention. CIN was occurred less frequently, though statistically insignificant, in curcumin group (22.7%) compared with placebo group (32.3%).. It was found that although curcumin reduced the incidence of CIN, this difference was not statistically significant. It seems that, like other antioxidant substances studied in previous studies, although curcumin can reduce apoptosis and oxidative stress at cellular level, but in high risk patients for CIN, such as patients with renal insufficiency, it does not produce more protective effects than hydration with normal saline.

Topics: Contrast Media; Coronary Angiography; Creatinine; Curcuma; Curcumin; Humans; Kidney Diseases; Plant Extracts; Prospective Studies; Treatment Outcome

Gentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use.. The present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats.. Pre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50 mg/dL), blood urea nitrogen (from 35.00 to 23.50 mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment.. Our findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Apoptosis; Creatinine; Curcumin; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Gentamicins; Kidney Diseases; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Aristolochic acid I (AA-I), presenting in a variety of natural medicinal plants, which could cause tubular epithelial cell injury. Curcumin (CUR), a polyphenolic substance isolated from turmeric, is a natural antioxidant. The aim of this experiment was to investigate whether CUR attenuated AA-I-induced renal injury in rats through the SIRT1/Nrf2/HO-1 signaling pathway. SD rats were treated with AA-I (10 mg/kg) or/and CUR (200 mg/kg) for 28 days to assess the protective effect of CUR on AA-I-induced renal injury in vivo. NRK-52E cells were treated with AA-I (40 μ M) or/and CUR (20 μ M) for 24 h in vitro. The intervention pathway of CUR against oxidative stress injury induced by AA-I was assessed by observing pathological changes, oxidative stress status, apoptosis and the expression of SIRT1/Nrf2/HO-1 signaling pathway-related factors. The results showed that AA-I exposure increased the contents of BUN, Cr, KIM-1, NGAL, ALT and AST in serum. It increased the content of MDA, decreased the activities of SOD, GST, GSH and the content of ATP in renal tissue. Pathological changes such as inflammatory cell infiltration and mitochondrial injury occurred in renal tissue. AA-I exposure resulted in a substantial rise in the levels of BAX, Ccaspase-9, Cleaved Caspase-9, Caspase-3, Cleaved Caspase-3 and a significant decrease in mRNA and protein expression levels of Bcl-2, SIRT1, Nrf2, NQO1, HO-1 and Keap1. However, these changes were reversed by CUR intervention. In summary, AA-I exposure caused mitochondrial dysfunction and triggered apoptosis through the oxidative stress pathway. However, CUR could reduce AA-I-induced renal injury by activating the SIRT1/Nrf2/HO-1 signaling pathway.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Apoptosis; Aristolochic Acids; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Curcumin; Kelch-Like ECH-Associated Protein 1; Kidney Diseases; Lipocalin-2; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Sirtuin 1; Superoxide Dismutase

The present work was conceptualized to determine the potential protective effects of curcumin on arsenic-induced kidney damage in male albino rat model. Thirty six male albino rats were selected, weighed about 175±10g and classified into four groups (9 rats in each group) such as C group (control with basal diet), Cur group (curcumin 200mg/kg body weight), AI group (arsenic-induced 5mg/kg body weight) and AI + Cur group (arsenic 5mg/kg+curcumin 200mg/kg body weight), respectively. Arsenic and curcumin were offered through the gavage method once daily with basal diet. The different analyzed parameters showed that arsenic-induced elevation of aspartate amino transferase, alkaline phosphatase, bilirubin urea, alanine aminotransferase and creatinine significantly decreased with curcumin application in AI + Cur group. Similarly, the statistically significant decline of low-density lipoprotein (LDL), cholesterol, triglyceride and increased in high-density lipoprotein (HDL) was observed in rats of AI + Cur group with curcumin treatment as compared to the rats of AI group. The level of different enzymes of the liver as well as kidney was noted depleted on arsenic exposure whereas increased in level was observed with curcumin application in AI + Cur group. Moreover, pathological histology changes were also recorded. The outcomes suggest that curcumin has a potential effect against arsenic-induced toxicity in biological model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arsenic; Chemical and Drug Induced Liver Injury; Curcumin; Hyperlipidemias; Kidney Diseases; Rats

The use of herb-based therapies is increasing over the past decades. These agents have been reported to provide many beneficial effects in many experimental and clinical studies. Curcumin is one of these agents which has potent pharmacological effects enabling it for the prevent and treatment of many diseases and pathologies such as renal disorders, hyperglycemia, oxidative stress, hypertension, and dyslipidemia. However, the exact molecular mechanisms mediating these renoprotective effects of curcumin are not well established. So, in the current study, we surveyed for possible renoprotective roles of curcumin and concluded how curcumin protects against renal injuries.

Topics: Antioxidants; Curcumin; Humans; Kidney; Kidney Diseases; Oxidative Stress

The aim: The current study was designed to examine the possible Nephroprotective effects of CMN in preventing nephrotoxicity and oxidative stress caused by chronic administration of CsA in rats.. Materials and methods: This study consisted of four groups and each group was made up of 8 rats. The first group was considered as a control group (received vehicle (0.9%N/S orally, and olive oil S.C), and the rest included the following: CMN group (received CMN in a dose of 30mg/kg/day orally), CsA group (received CsA in a dose of 20mg/kg/day S.C), and CMN plus CsA combination group (received CMN (30mg/kg/day, orally) plus CsA (20mg/kg/day, S.C) for 21days). For each group, the following variables wereassessed: Serum urea concentration, Serum creatinine concentration, initial body weight, final body weight, Tissue MDA level, Tissue GpX1 level, Tissue CAT level, Tissue SOD level, and tissue IL-2 level, and histopathological examination.. Results: Mean levels of serum urea and creatinine, tissue MDA, tissue IL-2, and histopathological scores are significantly (P<0.05) increased in the CsA group compared with the control, and CMN groups (normal renal tissue). Tissue SOD, CAT, and GpX1 activities are significantly (P<0.05) decreased in the CsA group compared with the control, and CMN group. Concomitant administration of CMN with CsA resulted in significantly (P<0.05) lower elevated levels of MDA, serum urea, and creatinine, significantly higher levels of antioxidant enzymes, and normalization of the altered renal morphology compared with CsA treated rats.. Conclusions: CMN has antioxidant and anti-inflammatory properties that protect the kidney from CsA's toxicity.

Topics: Animals; Curcumin; Cyclosporine; Kidney Diseases; Rats; Rats, Wistar; Renal Insufficiency

Curcumin (Cur) has been used extensively in dietary supplement with antioxidant and anti-apoptotic properties. Although dibutyl phthalate (DBP) has adverse effects on the kidney, any association between DBP exposure and the role of Cur is unclear. We tested the hypothesis that exposure to DBP has adverse consequences on renal dysfunction in mice and the potential protective role of Cur in decreasing DBP-induced renal dysfunction via inhibiting oxidative stress and apoptosis. Kidney function, oxidative stress biomarkers, and apoptosis factors as well as Bcl-2 and Bax were investigated. The results showed a marked increase of renal dysfunction, oxidative stress and apoptosis level after DBP exposure compared to the control. While administration of Cur to DBP-treated mice may reduce these adverse biochemical changes compared with DBP-alone group. Overall, these results suggest that oxidative stress and apoptosis are involved in DBP-induced renal disorder, whereas Cur plays a protective role in inhibiting these two pathways.

Topics: Animals; Animals, Outbred Strains; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Curcumin; Dibutyl Phthalate; Disease Models, Animal; Humans; Kidney Diseases; Male; Mice; Oxidative Stress; Protective Agents

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-κB/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro-fibrotic mechanisms, apoptosis, inflammatory response, and NF-κB and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-κB and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cholesterol; Chronic Disease; Curcumin; Cytokines; Diet, High-Fat; Kidney Diseases; Kidney Glomerulus; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; Obesity; Triglycerides

Topics: Animals; Curcumin; Epithelial-Mesenchymal Transition; Humans; Kidney; Kidney Diseases; Signal Transduction

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure.

Topics: Animals; Antioxidants; Apoptosis; Arsenic Trioxide; Autophagy; Curcumin; Ducks; Dyslipidemias; Kidney; Kidney Diseases; Oxidative Stress; Protective Agents; TOR Serine-Threonine Kinases

Fibrosis contributes to graft loss in chronic renal allograft injury. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrosis following kidney transplantation. Autophagy plays an important role in the homeostasis of diverse cell types including endothelial cells. Here we demonstrate that inhibition of autophagy by treatment with 3-methyladenine (3-MA) or by silencing autophagy-related (ATG)5 promoted interleukin (IL)-6-dependent EndMT in human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs), and autophagy inactivation was associated with EndMT in patients with chronic allograft dysfunction. IL-6 level was significantly higher in the culture medium of HUVECs transfected with ATG5 siRNA or treated with 3-MA compared to the respective control groups. IL-6 application induced EndMT in HUVECs and HRGECs, whereas antibody-mediated neutralization of IL-6 suppressed EndMT induced by ATG5 silencing. The protective role of curcumin (Cur) against allograft fibrosis was confirmed in a rat kidney transplantation model of F344 donors to Lewis recipients. Curcumin-a natural polyphenol compound with known antifibrotic effects in various tissues-alleviated IL-6-induced EndMT and promoted autophagy in the allografted organ and in HUVECs. This is the first demonstration of the role of autophagy in renal allograft fibrosis; our findings indicate that curcumin can alleviate chronic renal allograft injury by suppressing IL-6-dependent EndMT

Topics: Adult; Allografts; Animals; Autophagy; Biomarkers; Biopsy; Curcumin; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibrosis; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; Immunosuppressive Agents; Interleukin-6; Kidney Diseases; Kidney Transplantation; Male; Models, Biological; Rats

Renal fibrosis is a progressive process resulting from a sustained injury that may ultimately cause renal failure. Cisplatin is an antitumor drug that induces renal injury and nephrotoxicity and is widely employed as a model for acute and chronic renal injury. Several signaling pathways are implicated in fibrogenic cell activation among which is Hedgehog (Hh) signaling. We here investigated the effects of arsenic trioxide (Ars) and curcumin in ameliorating cisplatin-induced kidney fibrosis via regulating Hh signaling. Cisplatin (4.5 mg/kg) was administered in Sprague-Dawley rats for two consecutive days and renal fibrosis was induced after 21 days. Once renal fibrosis was confirmed, Ars (3.5 mg/kg/day, orally) and curcumin (200 mg/kg/day, orally) were administered daily for another 21 days. Ars and curcumin corrected kidney function markers as creatinine clearance and urea nitrogen. Both agents ameliorated fibrosis as shown by lowered TGF-β1 mRNA levels, α-SMA protein levels, and hydroxylproline content. Cisplatin-activated Hh signaling which was blocked by both Ars and curcumin as demonstrated by decreased mRNA levels of Shh, Smo, and Ptch and suppressed renal Gli1 and Gli2 protein levels. Our results indicate new therapeutic roles for Ars and curcumin and suggest that blocking Hh signaling may be a promising approach for alleviating renal fibrosis. Symbols indicate α-SMA, alpha-smooth muscle actin; TGF-β, transforming growth factor-beta; Ptch, patched; Smo, smoothened; Shh, sonic hedgehog; Ihh, Indian hedgehog; Dhh, desert hedgehog; and SUFU, suppressor of fused.

Topics: Animals; Antineoplastic Agents; Arsenic Trioxide; Cisplatin; Curcumin; Drug Delivery Systems; Drug Therapy, Combination; Fibrosis; Hedgehog Proteins; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Signal Transduction

The prevalence of diabetes in the world is increasing rapidly. Kidney diseases are among the most common medical disorders. The aim of this study was to investigate the effect of curcumin on the diabetic kidney. Thirty-five female Wistar albino rats were divided into seven groups. No procedure was performed on the Cont group. The Sham group received corn oil via gavage for 14 days. The curcumin (Curc) group received 30-mg/kg curcumin for 14 days, while the diabetes mellitus (DM) group received 50-mg/kg streptozotocin (STZ) in a single dose intraperitoneally. The DM + curcumin 1 (DC1) group received 30 mg/kg curcumin for 14 days, seven days after the application of STZ, while the DM + curcumin 2 (DC2) received 30 mg/kg curcumin for 14 days, 21 days after the application of STZ, and the DM + curcumin 3 (DC3) group received single-dose STZ at the same time as the application of 30 mg/kg curcumin for 14 days. Medulla, cortex, tubule, and glomerulus volume ratios were calculated using stereological techniques. Cortex volumes in the Sham and DM groups were significantly lower than in the Cont group (p < 0.05). The cortex volume in the DC3 group was also significantly lower than in the Curc group (p < 0.05). Medullary volume was significantly higher in the DC3 group compared to the DM group (p < 0.05). Curcumin was determined to exhibit a protective effect on the diabetic kidney since the glomerulus in the curcumin-exposed group exhibited a well-protected structure following experimentally induced diabetes based on light and electron microscopic analysis findings. These findings suggest that curcumin used following experimentally induced diabetes exhibits protective effects on the diabetic kidney.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Female; Immunohistochemistry; Kidney; Kidney Diseases; Microscopy, Electron; Rats, Wistar; Streptozocin

Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects.. To explore the mechanisms underlying the effects of curcumin on RIF.. Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-β1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation.. Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.

Topics: Animals; Anti-Inflammatory Agents; Blood Urea Nitrogen; Cell Line; Curcumin; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Kidney Diseases; Male; Mice, Inbred C57BL; NF-kappa B; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Toll-Like Receptor 4; Ureteral Obstruction

This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney.. Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups.. A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group.. Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Cyclosporine; Gene Expression Regulation; Glomerular Filtration Rate; Immunosuppressive Agents; Kidney Diseases; Male; Metalloproteins; Podocytes; Rats; Rats, Wistar

The aim of this study was to evaluate the effects of curcumin in an experimental model of busulfan-induced renal toxicity with emphasis on importance of histological alterations.. In this study, we utilized 32 adult male Wistar rats (250 ± 10 g). All the animals were divided into four experimental groups randomly: (I) Control; (II) Busulfan (40 mg/kg); (III) Olive oil; and (IV) Curcumin (80 mg/kg/day). Finally, the rats were euthanized and kidney tissues were taken for histopathology experiments, serum BUN, and creatinine level, reactive oxygen species (ROS) production and glutathione disulfide (GSH) activity.. Our result showed that the reduction in body weight and kidney weight in busulfan groups in comparison with the control and curcumin groups. The result in this study also showed that the reduction in BUN, creatinine, and ROS production in curcumin groups in comparison with the busulfan group together with an increasing of GSH activity compared to busulfan induced rats.. Our results of this study indicated that that the reduction in body weight, kidney weight, total volume of kidney, total length of nephron tubules, and numerical density of glomeruli and nephron tubules in busulfan groups in comparison with the control and curcumin groups However, curcumin can be an alternative choice for therapeutically and research purposes in the disturbing kidney after treatment with busulfan.

Topics: Animals; Antioxidants; Busulfan; Curcumin; Disease Models, Animal; Injections, Intravenous; Kidney Diseases; Kidney Tubules; Male; Oxidative Stress; Rats; Rats, Wistar

Cisplatin (CP) is a potent anticancer drug used to treat solid tumors. Its use, however, is dose-limited by its nephrotoxicity. We aimed to compare the effect of melatonin and curcumin given singly, with that of a combination of these two agents on CP-induced nephrotoxicity in rats. CP (6 mg/kg, given once intraperitoneally) induced nephrotoxicity as evidenced by several significant adverse physiological, biochemical and histopathological actions that included a reduction in body weight, increased urine production, and significant alterations in some conventional and novel renal damage indices in plasma, urine and kidneys. CP also elevated several pro-inflammatory cytokines and caused renal oxidative/nitrosative stress. Supplementation with either curcumin (200 mg/kg) or melatonin (10 mg /kg) given singly by oral gavage for eight consecutive days prior to CP injection and four days thereafter, significantly mitigated the adverse renal effects of CP, by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in renal tissues of CP- treated rats. When curcumin and melatonin were given together, the ameliorative effect was augmented in some of the measured indices e.g. tumor necrosis factor alpha, cystatin C, uric acid, phosphorus in plasma and, urine creatinine and creatinine clearance. Renal platinum concertation was reduced more with curcumin than that with melatonin, while the reduction was maximized when both melatonin and curcumin were given. Pending further pharmacological and toxicological studies, a combination of these two agents is likely to be mor effective in mitigating the adverse renal effects of CP administered to cancer patients.

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Cisplatin; Curcumin; Cytokines; Drug Therapy, Combination; Inflammation Mediators; Kidney Diseases; Male; Melatonin; Nitrosative Stress; Oxidative Stress; Rats; Rats, Wistar

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Curcumin; Drug Therapy, Combination; Gamma Rays; Inflammation Mediators; Kidney Diseases; Male; Oxidative Stress; Rats; Rats, Wistar; Silymarin

Curcumin (Cur) effects on renal injury induced by zinc oxide nanoparticles (NZnO) in rats were investigated. NZnO at a dose of 50 mg/kg for 14 days was administered to rats as intoxicated group. In protection group, Cur at a dose of 200 mg/kg was administered for 7 days prior to NZnO treatment and followed by concomitant administration of NZnO for 14 days. Plasma concentrations of uric acid, creatinine (Cr), and blood urea nitrogen (BUN) were detected to evaluate renal injury. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were determined for evaluation oxidative stress. TUNEL staining and histological changes were also performed. Administration of NZnO caused a significant elevation in the uric acid, Cr, and BUN levels. Oxidative stress was increased in the kidney by NZnO through enhancing MDA contents and reducing activities of SOD and GPx enzymes. According to histological examinations, treatment with NZnO caused proximal tubule damages, which was accompanied by the accumulation of red blood cells, infiltration of inflammatory cells, and reducing glomerular diameters. Significant increase was observed in the apoptotic index of the renal tubules in NZnO-treated rats. In present work, pretreatment of Cur reduced the histological changes, decreased biomarker levels, attenuated apoptotic index, and ameliorated oxidative stress by decreasing the MDA contents and increasing the activities of SOD and GPx enzymes. These findings indicate that Cur effectively protects against NZnO-induced nephrotoxicity in the rats.

Topics: Animals; Antioxidants; Blood Urea Nitrogen; Creatinine; Curcuma; Curcumin; Glutathione Peroxidase; Kidney; Kidney Diseases; Male; Malondialdehyde; Nanoparticles; Oxidative Stress; Phytotherapy; Plant Extracts; Protective Agents; Rats, Wistar; Superoxide Dismutase; Zinc Oxide

The aim of this study was to compare the potential renoprotective effects of turmeric (TM) and nano turmeric (NTM) with those of desferrioxamine (DSM) against copper sulfate (CS)-induced toxicity. Rats were administered a toxic dose of CS with TM, NTM, and DSM for 1 week. Next, serum-urea creatinine, uric acid, interleukin (IL)-10, c-reactive protein (CRP), and caspase-3 levels; renal nitric oxide (NO), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), vascular cell adhesion molecule-1 (VCAM-1), kidney injury molecule (KIM)-1, signal transducer and activator of transcription 3 (STAT-3) protein expression; and nuclear factor (NF)-κB and B-cell lymphoma -2 (Bcl-2) messenger RNA expression levels were estimated. Administration of the investigated antioxidants downregulated the marked increase in urea, creatinine, uric acid, CRP, caspase-3, NO, MDA, VCAM-1, kidney injury molecule (KIM-1), STAT-3, NF-κB, and DNA fragmentation, and increased Bcl-2, IL-10, GSH, and SOD levels induced by CS. The histopathological examination confirmed the effects of the antioxidants on the investigated biochemical parameters. Interestingly, NTM exhibited a superior renoprotective effect, which was comparable with that of DSM. In conclusion, NTM was shown to be a promising candidate against CS-induced toxicity, and several molecular mechanisms were implicated in the CS-induced renotoxicity as well as the treatment effects of NTM.

Topics: Animals; Cell Adhesion Molecules; Copper Sulfate; Curcumin; Drug Evaluation, Preclinical; Female; Gene Expression Regulation; Kidney Diseases; Rats; STAT3 Transcription Factor; Vascular Cell Adhesion Molecule-1

The aim of this registry was to evaluate the efficacy of Meriva® in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. TKD was a casual finding on urinary tests after reported side effects following drug consumption, a clinical event or dehydration.. Patients followed either standard management (SM) or SM plus Meriva® (Curcumin Phytosome®) supplementation (3 capsules/day, corresponding to 1.5 g of Meriva® containing 300 mg of curcumin in a bioavailable delivery form). The follow-up period lasted 4 weeks. Subjects were divided according to macroalbuminuria (>300 mg albumin on 24 hours) or microalbuminuria (<300 mg/day albuminuria).. Albuminuria decreased in all subjects, with a statistically significant improvement in the supplement group compared with controls (P<0.05). Oxidative stress level was high in all microalbuminuria subjects at inclusion; it was significantly more reduced in the supplement group (P<0.05) after 4 weeks. During follow-up blood pressure values were controlled; all subjects were under one single antihypertensive. Blood and urinary tests at 4 weeks were normalized in all subjects. Fatigue was significantly decreased or disappeared in most supplemented subjects at 4 weeks, with better results than in controls. Compliance and tolerability to Meriva® were good.. This registry study indicates that albuminuria - marker of TKD - is safely ameliorated with the standardized supplement Meriva®. Studies are needed to evaluate the effect of Meriva® in subjects with more significant clinical conditions (i.e. diabetics) or risk factors.

Topics: Adult; Albuminuria; Blood Pressure; Curcumin; Dietary Supplements; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Oxidative Stress; Plant Extracts; Registries; Renal Insufficiency

This study explored the potential value of curcumin, a natural product, in the protection of CsA‑induced nephrotoxicity. The aim of the present study was to investigate the effects of curcumin on Cyclosporine A (CsA)‑induced renal oxidative stress and determine the potential underlying molecular mechanisms of the renal protective effects of Cur. HK‑2 human renal cells were co‑treated with CsA and various doses of Cur. Cell survival rate was determined by an MTT assay, total cellular protein was collected and oxidative stress in cell homogenates was evaluated by determining the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and catalase (CAT), the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and total antioxidant capacity. Furthermore, Bcl‑2 and Bcl‑2‑associated X (Bax) protein expression was measured by western blot analysis. In addition, a CsA‑induced nephrotoxicity (CAN) rat model was also established. Renal function was analyzed by measuring creatinine (Crea) and blood urea nitrogen (BUN) in the serum of rats, and histopathological examination was performed on renal tissues using hematoxylin and eosin staining, periodic acid‑Schiff staining and nuclear factor‑κB (NF‑κB) immunostaining. The results demonstrated that treatment of HK‑2 cells with CsA significantly increased ROS and MDA levels, and decreased the activities of SOD, GSH‑Px and CAT, compared with the control group. However, these effects of CsA were dose‑dependently improved by treatment with Cur. In addition, Cur treatment increased Bcl‑2 and decreased Bax protein in HK‑2 cells, compared with cells treated with CsA alone. In the CAN rat model CsA (30 mg/kg) treatment significantly elevated serum Crea levels and BUN, but lowered endogenous Crea clearance rate, compared with the control group. Co‑administration of Cur with CsA significantly reversed the effects of CsA on serum Crea levels, BUN and Crea clearance rate (Ccr). Additionally, Cur alleviated CsA‑induced renal cell injury, as less vacuolar degeneration of glomerular cells was observed compared with the CsA alone group. In conclusion, Cur may increase renal antioxidant capacity and reduce the Bax/Bcl‑2 ratio, subsequently improving CsA‑induced renal failure and renal tubular deformation and cell vacuolization.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cell Line; Curcumin; Cyclosporine; Disease Models, Animal; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Male; Oxidative Stress; Protective Agents; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species

Curcumin is a polyphenol present in the rhizomes of the species Curcuma longa L. ("turmeric," Zingiberaceae), which has been used for centuries as an anti-inflammatory. We aimed to evaluate the anti-inflammatory effects of C. longa in renal injury induced by doxorubicin (DOX, 3.5 mg.kg

Topics: Administration, Oral; Albuminuria; Animals; Curcuma; Curcumin; Desiccation; Doxorubicin; Kidney; Kidney Diseases; Male; Plant Extracts; Powders; Rats; Rats, Wistar; Rhizome; Treatment Outcome; Zingiberaceae

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.

Topics: Animals; Blood Urea Nitrogen; Cisplatin; Coumaric Acids; Curcumin; Heme Oxygenase (Decyclizing); Kidney; Kidney Diseases; Male; Malondialdehyde; Peroxidase; Protective Agents; Rats, Wistar; RNA, Messenger; Tyrosine

Exposure to drugs often results in toxicity in the kidney which represents the major control system maintaining homeostasis of the body and thus is especially susceptible to xenobiotics. Nephrotoxicity is a life-threatening side-effect of nonsteroidal anti-inflammatory drugs (NSAIDs). Diclofenac is one of the most frequently prescribed NSAIDs and have been reported to cause multiple organs damage. Curcumin (CUR) exhibits nephroprotective properties. Therefore, rats were divided into four groups; rats of groups 3 and 4 received diclofenac (100 mg/kg, i.m.), whereas rats of groups 2 and 4 received CUR (100 mg/kg, p.o.) for 3 days. Diclofenac revealed a significant increase in urea and creatinine levels and malondialdehyde concentration and marked reduction in catalase activity and reduced glutathione concentration. Histopathologically, diclofenac produced fatty changes and eosinophilic casts were detected in the renal tubules, those were attenuated by administration of CUR prior diclofenac.

Topics: Animals; Curcumin; Diclofenac; Kidney Diseases; Kidney Tubules, Distal; Male; Rats

Sodium arsenite is an environmental pollutant with the ability to generate free radicals and curcumin acts as a potent antioxidant. This study investigates the effect of curcumin on kidney histopathology, lipid peroxidation and antioxidant capacity of serum in the mice treated with sodium arsenite. Adult male mice were divided into four groups: control, sodium arsenite, curcumin and curcumin+sodium arsenite. The treatments were delivered for 5 weeks. After the treatment period, blood samples were collected and the concentrations of malondialdehyde (MDA) and total antioxidant capacity of serum were determined. Left kidney was dissected, weighed and used for histopathological and histomorphometrical studies. Sodium arsenite-treated mice showed a significant decrease in the diameter of glomerulus and proximal tubule, glomerular area, total antioxidant capacity of serum as well as a significant increase in serum concentration of MDA compared to the control group. However, no significant difference was found in kidney weight, area and diameter of Bowman's capsule as well as the diameter of distal tubule in mice treated with sodium arsenite compared to the control. In curcumin+sodium arsenite group, curcumin significantly reversed the adverse effects of sodium arsenite on the diameter of glomerulus and proximal tubule, glomerular area, total antioxidant capacity of serum and serum concentration of MDA compared to the sodium arsenite group. The application of curcumin alone significantly increased the total antioxidant capacity of serum compared to the control. Curcumin compensated the adverse effects of sodium arsenite on kidney tissue, lipid peroxidation and total antioxidant capacity of serum.

Topics: Animals; Antioxidants; Arsenites; Curcumin; Enzyme Inhibitors; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Mice; Sodium Compounds

Arsenic exposure through drinking water causes oxidative stress and tissue damage in the kidney and brain. Curcumin (CUR) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, which can be overcome by the encapsulation of CUR with nanoparticles (NPs). The present study investigates the therapeutic efficacy of free CUR and NP-encapsulated CUR (CUR-NP) against sodium arsenite-induced renal and neuronal oxidative damage in rat. The CUR-NP prepared by emulsion technique and particle size ranged between 120 and 140 nm, with the mean particle size being 130.8 nm. Rats were divided into five groups (groups 1-5) with six animals in each group. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in Group 2; however, these animals were also administered with empty NPs, CUR (100 mg/kg body weight), and CUR-NP (100 mg/kg), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic exposure significantly increased serum urea nitrogen and creatinine levels. Arsenic increased lipid peroxidation (LPO), reduced glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were depleted significantly in both kidney and brain. Treatment with free CUR and CUR-NP decreased the LPO and increased the enzymatic and nonenzymatic antioxidant system in kidney and brain. Histopathological examination showed that kidney and brain injury mediated by arsenic was ameliorated by treatment. However, the amelioration percentage indicates that CUR-NP had marked therapeutic effect on arsenic-induced oxidative damage in kidney and brain tissues.

Topics: Administration, Oral; Animals; Antioxidants; Arsenic; Brain Chemistry; Brain Diseases; Curcumin; Kidney; Kidney Diseases; Male; Nanoparticles; Oxidative Stress; Particle Size; Rats; Rats, Wistar

Curcumin is a polyphenol and cisplatin is an antineoplastic agent that induces nephrotoxicity associated with oxidative stress, apoptosis, fibrosis and decrease in renal tight junction (TJ) proteins. The potential effect of curcumin against alterations in TJ structure and function has not been evaluated in cisplatin-induced nephrotoxicity. The present study explored whether curcumin is able to prevent the cisplatin-induced fibrosis and decreased expression of the TJ and adherens junction (AJ) proteins occludin, claudin-2 and E-cadherin in cisplatin-induced nephrotoxicity. Curcumin (200 mg kg(-1)) was administered in three doses, and rats were sacrificed 72 h after cisplatin administration. Curcumin was able to scavenge, in a concentration-dependent way, superoxide anion, hydroxyl radical, peroxyl radical, singlet oxygen, peroxynitrite anion, hypochlorous acid and hydrogen peroxide. Cisplatin-induced renal damage was associated with alterations in plasma creatinine, expression of neutrophil gelatinase-associated lipocalin and of kidney injury molecule-1, histological damage, increase in apoptosis, fibrosis (evaluated by transforming growth factor β1, collagen I and IV and α-smooth muscle actin expressions), increase in oxidative/nitrosative stress (evaluated by Hsp70/72 expression, protein tyrosine nitration, superoxide anion production in isolated glomeruli and proximal tubules, and protein levels of NADPH oxidase subunits p47(phox) and gp91(phox), protein kinase C β2, and Nrf2) as well as by decreased expression of occludin, claudin-2, β-catenin and E-cadherin. Curcumin treatment prevented all the above-described alterations. The protective effect of curcumin against cisplatin-induced fibrosis and decreased proteins of the TJ and AJ was associated with the prevention of glomerular and proximal tubular superoxide anion production induced by NADPH oxidase activity.

Topics: Adherens Junctions; Animals; Antioxidants; Biomarkers; Cisplatin; Curcumin; Fibrosis; Free Radical Scavengers; Kidney Diseases; Male; NADPH Oxidases; Oxidative Stress; Protein Kinase C beta; Protein Subunits; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxides; Tight Junctions

Curcumin (Cur) and gallic acid (Gal) are major food additives. Cur has well-known antioxidant properties, whereas Gal has both antioxidant and pro-oxidant effects. The present study investigated the effects of oral administration of Gal with or without Cur on antioxidant enzymes activities, glutathione (GSH) and the enzymes in its metabolism in rat liver in vivo and markers of tissue damage in the serum. Results showed that the increase in serum creatinine level, alkaline phosphatase and lactate dehydrogenase activities by Gal treatment were inhibited by combined administration of Gal and Cur. The decrease in GSH-peroxidase, GSH-S-transferase, superoxide dismutase and GSH-reductase activities by Gal treatment were inhibited when both Gal and Cur were administered together. The malondialdehyde concentration and catalase activity were significantly increased following administration of Gal but not when the administration of Gal was combined with Cur. Finally, the increase in GSH level was seen following administration of Cur alone or in combination with Gal but not with Gal alone. These results suggest that Gal might induce oxidative stress in the rat liver and affect renal function that can be inhibited by the combined administration of Gal and Cur.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Curcumin; Gallic Acid; Glutathione; Kidney Diseases; Male; Oxidation-Reduction; Oxidative Stress; Protective Agents; Rats; Rats, Wistar

In the present study, a new series of 2-amino-pyran-3-carbonitrile derivatives of curcumin 2-7 have been synthesized via one-pot simple and efficient protocol, involving the reaction of curcumin 1 with substituted-benzylidene-malononitrile to modify the 1,3-diketone moiety. The structures of the synthesized compounds 2-7 were elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. The nephroprotective mechanism of these new curcumin analogues was evaluated on the post-gamma-irradiation (7 Gy) - induced nephrotoxicity in rats. Activation of Nrf2 by these curcumin analogues is responsible for the amendment of the antioxidant status, impairment of NF-κB signal, thus attenuate the nephrotoxicity induced post-γ-irradiation exposure. 4-Chloro-phenyl curcumin analogue 7 showed the most potent activity. In conclusion, the results of the present study demonstrate a promising role of these new curcumin analogues to attenuate the early symptoms of nephrotoxicity induced by γ-irradiation in rats via activation of Nrf2 gene expression. These new curcumin analogues need further toxicological investigations to assess their therapeutic index.

Topics: Animals; Antioxidants; Biomarkers; Blotting, Western; Caspase 3; Curcumin; DNA Fragmentation; Electrophoresis, Agar Gel; Gamma Rays; Gene Expression Regulation; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Diseases; Kidney Function Tests; Male; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; Rats; Stereoisomerism; Trace Elements; Vascular Cell Adhesion Molecule-1

The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7 mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100 mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p<0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p<0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p<0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p<0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p<0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Blood Urea Nitrogen; Cisplatin; Creatinine; Curcumin; Glutathione; Kidney; Kidney Diseases; Male; Nicotinamide Phosphoribosyltransferase; Rats; Rats, Wistar; Sirtuins; Treatment Outcome

The adverse effects of anticancer drugs can prompt patients to end their treatment despite the efficacy. Cisplatin is a platinum-based molecule widely used to treat various forms of cancer, but frequent and long-term use of cisplatin is limited due to severe nephrotoxicity. In the present study, we investigated the protective effect and mechanism of tetrahydrocurcumin on cisplatin-induced kidney damage, oxidative stress, and inflammation to evaluate its possible use in renal damage. Cisplatin-induced LLC-PK1 renal cell damage was significantly reduced by tetrahydrocurcumin treatment. Additionally, the protective effect of tetrahydrocurcumin on cisplatin-induced oxidative renal damage was investigated in rats. Tetrahydrocurcumin was orally administered every day at a dose of 80 mg/kg body weight for ten days, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) in 0.9 % saline on day four. The creatinine clearance levels, which were markers of renal dysfunction, in cisplatin-treated rats were recovered nearly back to normal levels after administration of tetrahydrocurcumin. Moreover, tetrahydrocurcumin exhibited protective effects against cisplatin-induced oxidative renal damage in rats by inhibiting cyclooxygenase-2 and caspase-3 activation. These results collectively provide therapeutic evidence that tetrahydrocurcumin ameliorates renal damage by regulating inflammation and apoptosis.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Biomarkers; Caspase 3; Cisplatin; Curcuma; Curcumin; Cyclooxygenase 2; In Vitro Techniques; Kidney; Kidney Diseases; LLC-PK1 Cells; Male; Oxidative Stress; Phytotherapy; Plant Extracts; Rats, Wistar; Swine

Lead (Pb(2+)) toxicity is the most common form of heavy metal intoxication in humans and animals. Therefore, the current study was conducted to evaluate the potential ameliorative effects of curcumin on lead acetate (LA)-induced deleterious effects in the liver and kidney. Forty male Wistar rats were divided into four equal groups; first group was used as a control and given both corn oil orally and vehicle of lead acetate intraperitoneally (i.p). Groups from 2-4 were treated with lead acetate (LA; 50 mg/kg BW i.p), curcumin (200 mg/kg BW orally), and curcumin plus lead acetate, respectively. Curcumin was administered 3 weeks before LA injection for 7 days. Pb(2+)-intoxicated rats have higher Pb(2+) levels compared to other treated groups. Results revealed that lead acetate significantly increased the serum levels of hepatic transaminases (GPT and GOT), urea and creatinine, while albumin was significantly decreased. In parallel, serum IgG, IgM, and IgA were significantly decreased in LA-injected rats. LA groups showed decrease in messenger RNA (mRNA) expression of catalase, SOD, GST, GPx, and alpha-1 acid glycoprotein (AGP), while the gene expression of desmin, vimentin, transforming growth factor-β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and alpha-2 macroglobulin (α-2M) was increased. Prior and coadministration of curcumin with LA for 7 days significantly improved the ameliorated changes in liver and kidney, immunoglobulins, and mRNA expression. Moreover, curcumin ameliorated LA-induced congestion of hepatic and renal blood vessels and decreased fibrous tissue proliferation and necrosis of hepatocytes. In the kidney, LA-induced degeneration in tubular epithelium and intraluminal hyaline casts and prior curcumin administration restored normal renal structure with mild congestion of renal blood vessels. The results clarify the potential of curcumin to counteract the immunosuppressive alteration in gene expression as well as hepatic and renal damage occurred after Pb(2+) intoxication.

Topics: Acute-Phase Proteins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Catalase; Chemical and Drug Induced Liver Injury; Curcumin; Cytokines; Gene Expression; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Intermediate Filament Proteins; Kidney; Kidney Diseases; Liver; Male; Organometallic Compounds; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase

This study aims to evaluate the protective role of curcumin (Curc) against hematological and biochemical changes, as well as renal pathologies induced by lead acetate [Pb (CH3COO)2·3H2O] treatment. Male albino rats were intraperitoneally treated with Pb(2+) (25 mg of lead acetate/kg b.w., once a day) alone or in combination with Curc (30 mg of Curc/kg b.w., twice a day) for 7 days. Exposure of rats to Pb(2+) caused significant decreases in hemoglobin (Hb) content, hematocrit (Ht) value, and platelet (Plt) count, while Pb(2+)-related leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia, and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum of Pb(2+) group compared to that of control. Furthermore, significantly high levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density lipoprotein (HDL-C) level were also seen in blood after injection of Pb(2+). Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb(2+) produced marked histo-cytological alterations in the renal cortex. Co-administration of Curc to the Pb(2+)-treated animals restored most of the parameters mentioned above to near-normal levels/features. In conclusion, Curc appeared to be a promising agent for protection against Pb(2+)-induced toxicity.

Topics: Animals; Antioxidants; Blood Cell Count; Curcumin; Hematocrit; Hemoglobins; Kidney; Kidney Diseases; Kidney Function Tests; Lead; Lead Poisoning; Lipid Peroxidation; Male; Oxidative Stress; Platelet Count; Rats

To observe the effect and mechanism of curcumin derivative B06 on kidney from rats with hyperlipidemia and type 2 diabetes.. Thirty five male SD rats were randomly divided into five groups(n = 7): the normal control group, high-fat group, high-fat + B06-treatd group, diabetic group, diabetic + B06-treated group. After fed with high-fat diet for 4 weeks, the later two groups were in- jected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. B06-treated groups were given B06 by gavage at a dosage of 0.2 mg/kg . d for 8 weeks. After the treatment, the serum creatinine, blood urea nitrogen and uric acid were detected biochemically, the morphology of kidney was observed with light and transmission electron microscopy, the expression of collagen fibers was observed with Masson staining, the protein expression of collogen IV and fibronectin in kidney were determined by Immunohistochemistry.. It was showed that the levels of the serum creatinine and blood urea nitrogen elevated significantly in diabetic group. In high-fat and diabetic groups, increased glomerular mesangial matrix and collagen fiber and thicken glomerular basal membrane were observed under light microscopy, swelling and fusion of foot process were found under electron microscope; increased green matrix within glomeruli was observed under Masson staining. collogen IV and fibronectin protein expression were significantly enhanced in high-fat group and diabetic group. After B06's intervention, the levels of serum creatinine and blood urea nitrogen were decreased in diabetic groups, the morphological change of kidney was obviously relieved, Collogen IV and fibronectin protein expression reduced.. Curcumin derivative B06 exerts a protective effect on kidney in type 2 diabetic rats, reduced expressions of collogen IV and fibronectin, inhibition of the accumulation of extracellular matrix and glomerular mesangial proliferation, and then prevention of renal fibrosis may be the mechanism.

Topics: Animals; Blood Urea Nitrogen; Collagen Type IV; Creatinine; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Fibronectins; Kidney; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Streptozocin; Uric Acid

Aflatoxin contamination of foods is a worldwide problem. Chronic aflatoxin exposure is associated with kidney damage. Curcumin is a herbal agent, used in medicine with a wide range of beneficial therapeutic effects.. to evaluate the effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats.. Forty adult male rats were included and they were divided equally into 4 groups (10 rats each): Group I (control group), group II (Curcumin group): The rats received curcumin (200 mg/kg b.w.) orally by gastric tube for 5 days/week, group III (Aflatoxin B1 group): The rats received aflatoxin B1 (250 μg/kg b.w./day) orally by gastric tube 5 days/week for 4 weeks, group IV (Aflatoxin B1 and Curcumin group): The rats received aflatoxin and curcumin orally by gastric tube 5 days/week for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin, Masson's trichrome, Periodic acid Schiff, immunohistochemical detection of desmin and Bcl2.. The tubules of group III showed degenerative and necrotic changes with disruption of basal lamina. There was a significant decrease Bcl2 expression in the tubules, but the glomeruli showed an enlargement with dilation of their capillaries lumina in some areas, while the other areas showed glomerular atrophy with obliteration of their capillaries lumina. There was a significant increase in desmin expression in the glomerular cells. The interstitium showed hemorrhage and cellular infiltration. Group IV showed improvement of the histological and immunohistochemical changes described before.. Aflatoxin B1 has deleterious effects of on the histological structure of the rat's renal cortex and curcumin minimized these effects as it has antioxidant, anti-inflammatory and antiapoptotic activities. We advise eating nutritious diets that contain sufficient amounts of curcumin and regulation must implement to avoid the presence of aflatoxins in high concentrations in human food.

Topics: Aflatoxin B1; Animals; Apoptosis; Curcumin; Cytoprotection; Desmin; Disease Models, Animal; Immunohistochemistry; Kidney Cortex; Kidney Diseases; Male; Mycotoxicosis; Necrosis; Protective Agents; Proto-Oncogene Proteins c-bcl-2; Rats

Curcumin, a polyphenol, has pharmacological effects including antioxidant, anti-inflammatory and anti-cancer features. In this study, we have performed comparative in vivo evaluations of CDF (curcumin difluorinated) and curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) Control; (2) Cisplatin (7 mg/kg body wt, intraperitoneal as a single dose); (3) Cisplatin and CDF (50 mg/rat/day; for 12 days); (4) Cisplatin and curcumin (50 mg/rat/day), for 12 days). Cisplatin treated rats exhibited kidney injury manifested by increased serum N-urea and creatinine (P < 0.001). Kidney from cisplatin treated rats also exhibited significant increase in malondialdehyde (MDA) and 8-isoprostane levels (P < 0.001). Treatment with CDF and curcumin prevented the rise in serum N-urea, creatinine, MDA and 8-isoprostane as compared to experimental control group in kidney (P < 0.05). Compared to curcumin, CDF had greater potential in suppressing cisplatin-induced pro-inflammatory factors NF-κB and COX-2 as well as downstream markers Nrf2 and HO-1 (P < 0.05) in kidney. The analysis on anion transport markers (OAT1 and OAT3) showed a similar trend (CDF > curcumin). CDF could reduce the expression of multi-drug resistance markers OCT1, OCT2, MRP2 and MRP4 to a much greater extent than curcumin (P < 0.05). We also demonstrate that CDF influenced the expression of p-mTOR, p-p70S6K1, p-4E-BP1 and p-Akt. These data suggest that CDF can potentially be used to reduce the chemotherapy induced nephrotoxicity thereby enhancing the therapeutic window of cisplatin. The results also proved that compared to curcumin, CDF has superior protective effect in nephrotoxicity.

Topics: Animals; Antineoplastic Agents; Blood Urea Nitrogen; Cisplatin; Creatinine; Curcumin; Hydrocarbons, Fluorinated; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Multidrug Resistance-Associated Proteins; Organic Anion Transporters; Organic Cation Transport Proteins; Oxidative Stress; Rats; Rats, Wistar

Currently, the number of imaging and interventional procedures that use contrast agents (CAs) is gradually increasing. Oxidative stress plays a significant role in its pathophysiology. Curcumin (CC) is a natural substance with strong antioxidant efficacy.. In total, 24 male Wistar-albino rats were divided into four groups with seven rats in each group.. Biochemical measurements showed a significant increase (p < 0.001) in urea, creatinine and malondialdehyde (MDA) but a significant decrease (p < 0.001) in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) levels in the contrast-induced nephropathy (CIN) group compared with the control group. The immunohistochemical examination revealed a significant increase in autophagic and apoptotic cell death ratios and in the inflammatory signal (p < 0.05). Compared with the CIN group, a significant improvement in these unfavorable parameters was observed with CC therapy.. The preventive efficacy of CC against an experimental model of CIN has been demonstrated.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Autophagy; Biomarkers; Contrast Media; Curcumin; Cytoprotection; Disease Models, Animal; Iopamidol; Kidney; Kidney Diseases; Male; Nephritis; Oxidative Stress; Rats, Wistar

Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p = 1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.

Topics: Autophagy; Cells, Cultured; Curcumin; Drug Evaluation, Preclinical; Heme Oxygenase-1; Hemin; Humans; Hydrogen Peroxide; Kidney Diseases; Microtubule-Associated Proteins; Protective Agents; Protoporphyrins

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

Topics: Aldehyde Reductase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Biomarkers; Blotting, Western; Curcumin; Electron Transport Complex I; Enzyme Inhibitors; Hemodynamics; Kidney Diseases; Lipid Peroxidation; LLC-PK1 Cells; Male; Maleates; Mitochondria; Oxidation-Reduction; Oxidative Stress; Oxygen Consumption; Rats; Rats, Wistar; Reactive Oxygen Species; Swine

Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on.. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data.. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

Topics: Animals; Curcuma; Fibrosis; Kidney Diseases; Male; Metabolomics; Plant Oils; Proton Magnetic Resonance Spectroscopy; Rats, Sprague-Dawley; Time Factors; Ureteral Obstruction

To explore the effect of curcumin (CMN) on contrast-induced nephropathy (CIN) in rats and explore the potential mechanisms focusing on heme oxygenase-1 (HO-1) expression.. Male SD rats (n = 24) were randomly divided into four groups (n = 6 each): control group (group A), diatrizoate group (DTZ, group B), DTZ + CMN group (group C), DTZ + CMN + zinc protoporphyrin IX group (group D). All rats were fed with normal chow for 1 week, right kidney was excised under anesthesia and rats were fed with normal chow for another 4 weeks. Afterwards, rats in group A was fed with normal chow, and rats in group B to D were fed with low-salt diet. All rats were injected furosemide 2 mg×kg(-1)×d(-1) for 7 days intramuscularly. At the beginning of the 7(th) day, rats in group C were injected intramuscularly with CMN 20 mg/kg, rats in group D were injected with CMN (20 mg/kg) + zinc protoporphyrin IX (7.5 mg/kg) while rats in group A and B were injected with equal volume of physiological saline. At the end of the 7(th) day, indometacin (10 mg/kg) was injected into tail vein of all rats. One hour later, 60% DTZ (8 ml/kg) was injected to rats in the group B, C and D while equal volume saline was injected to rats in group A through common carotid artery. After 48 hours, blood was drawn from the hearts of deeply anesthetized rats and kidney tissue was obtained for histology, HO-1, Bax, Bcl-2 expression and the apoptotic index measurements.. The serum creatinine of group B, C and D [(83.67 ± 4.50) µmol/L, (63.67 ± 4.76) µmol/L, (104.17 ± 4.58) µmol/L] was significantly higher than that of group A [(41.50 ± 5.58) µmol/L, all P < 0.05], the serum creatinine was significantly higher in group B than in group C and lower than in group D (all P < 0.05). HO-1 expression of group B, C and D was significantly higher than that of group A (all P < 0.05), significantly higher in group C than in group B and D (all P < 0.05). HO-1 activity of group A, B and C was significantly higher than that of group D(all P < 0.05), HO-1 activity was significantly higher in group B than in group A and significantly lower in group B than in group C (all P < 0.05). Bax, Bcl-2 expression and apoptosis index of group B, C and D were significantly higher than that of group A (all P < 0.05), while Bcl-2/Bax of group B, C and D were significantly lower than that of group A (all P < 0.05). Bcl-2 and Bcl-2/Bax were significantly higher while apoptosis index was significantly lower in group C than in group B (all P < 0.05). Bax and apoptosis index were significantly higher and Bcl-2, Bcl-2/Bax were significantly lower in group D than in group B (all P < 0.05).. CMN could protect against contrast-induced nephropathy through reducing renal cell apoptosis via upregulating HO-1 expression and activating HO-1 activity in rats.

Topics: Animals; Contrast Media; Curcumin; Disease Models, Animal; Heme Oxygenase (Decyclizing); Kidney; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley

We hypothesized that curcumin, by increasing the expression of nuclear factor-erythroid-2-related factor 2 (Nrf2), could reduce oxidative stress, inflammation, and renal fibrosis in remnant kidney.. Sprague-Dawley rats were subjected to 5/6 nephrectomy and randomly assigned to untreated (Nx), curcumin-treated (75 mg/kg/day, orally), and telmisartan-treated groups (10 mg/kg/day, orally; as positive control). Sham-operated rats also served as controls. Five/sixth nephrectomy caused renal dysfunction, as evidenced by elevated proteinuria, blood urea nitrogen, and plasma creatinine, and decreased creatinine clearance that were ameliorated by curcumin or telmisartan treatment. The Nx rats demonstrated reduced Nrf2 protein expression, whereas the Kelch-like ECH-associated protein 1 was upregulated and heme oxygenase-1 level was significantly diminished. Consequently, Nx animals had significantly higher kidney malondialdehyde concentration and lower glutathione peroxidase activity, which was associated with the upregulation of nicotinamide adenine dinucleotide phosphatase oxidase subunit (p67(phox) and p22(phox) ), NF-kappaB p65, TNF-α, TGF-β1, cyclooxygenase-2, and fibronectin accumulation in remnant kidney. Interestingly, all of these changes were ameliorated by curcumin or telmisartan.. These findings demonstrate that, by modulating Nrf2-Keap1 pathway, the curcumin effectively attenuates oxidative stress, inflammation, and renal fibrosis, which suggest that curcumin hold promising potential for safe treatment of chronic kidney disease.

Topics: Animals; Benzimidazoles; Benzoates; Blood Pressure; Blood Urea Nitrogen; Creatinine; Curcumin; Cyclooxygenase 2; Fibronectins; Fibrosis; Heme Oxygenase (Decyclizing); Inflammation; Intracellular Signaling Peptides and Proteins; Kelch-Like ECH-Associated Protein 1; Kidney; Kidney Diseases; Male; Nephrectomy; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Proteinuria; Rats; Rats, Sprague-Dawley; Signal Transduction; Telmisartan; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

The administration of curcumin before and throughout the study attenuates oxidant stress and glomerular hemodynamic alterations induced by 5/6 nephrectomy (5/6NX). The purpose of this work was to study if curcumin is able to reverse established glomerular hemodynamic alterations (e.g. hyperfiltration and glomerular hypertension) and oxidant stress in rats with 5/6NX. Curcumin (120 mg/kg) was given to rats with established renal injury (30 days after surgery) and continued for 30 days (days 31-60 of the study). All rats were studied on day 60 after surgery. Curcumin was able (a) to reverse 5/6NX-induced glomerular hypertension and hyperfiltration, (b) to induce cell proliferation and nuclear translocation of Nrf2 and (c) to reverse 5/6NX-induced oxidant stress and decrease in antioxidant enzymes. These beneficial effects of curcumin were associated with the ability of this antioxidant to reverse renal structural alterations, proteinuria, hypertension, interstitial fibrosis, fibrotic glomeruli, tubular atrophy and mesangial expansion. It has been shown for the first time that curcumin is able to reverse established oxidants stress glomerular hypertension and hyperfiltration in rats with 5/6NX. These novel findings may play a key role in the attenuation of proteinuria and progression of renal damage in rats with 5/6NX. These data suggest that curcumin may be useful to reverse established hemodynamic alterations and renal injury in patients with chronic renal failure.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Pressure; Cell Nucleus; Curcumin; Drug Evaluation, Preclinical; Hemodynamics; Immunohistochemistry; Kidney Diseases; Kidney Glomerulus; Male; Nephrectomy; NF-E2-Related Factor 2; Oxidative Stress; Phytotherapy; Proteinuria; Rats; Rats, Wistar; Renal Circulation

Besides joint destruction, extra-articular complications (outside the locomotor system) are frequent in rheumatoid arthritis (RA) patients, especially cardiovascular, hematological and metabolic disorders. Here, we evaluated and compared the protective activity of two different doses of mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (GTaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (AIA).. Arthritis was induced by a single intra-dermal injection of 0.1 mL of Complete Freund's adjuvant (containing heat-killed Mycobacterium tuberculosis) into the palmar surface of the left hind paw after the rats were subjected to light diethyl ether anesthesia. Arthritic rats received orally and daily (for 28 consecutive days) distilled water as vehicle, indomethacin (1.0 mg/kg body weight), or GTaq (200 or 400 mg/kg body weight) from the day of arthritis induction.. The present study showed that GTaq (especially the high dose) was more effective (4.2-38.4% higher, P < 0.05-0.001) than indomethacin (a non-steroidal/anti-inflammatory drug) in alleviating the loss in body weight gain, the histopathological changes observed in ankle joints, blood leukocytosis and thrombocytosis, iron deficiency anemia, serum hypoalbuminemia and globulinemia, the impairment of kidney functions, and the risks for cardiovascular disease in arthritic rats. These protective effects of GTaq were mediated through increasing the food intake and decreasing the systemic inflammation that occur at the appearance of polyarthritis, oxidative stress and dyslipidemia.. Ginger-turmeric rhizomes mixture may be effective against RA severity and complications as shown in an AIA rat model.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Atherosclerosis; Biomarkers; Body Weight; Cardiovascular Diseases; Curcuma; Disease Progression; Dyslipidemias; Eating; Freund's Adjuvant; Humans; Indomethacin; Joints; Kidney; Kidney Diseases; Male; Oxidative Stress; Phytotherapy; Plant Preparations; Plants, Medicinal; Rats; Rats, Wistar; Rhizome; Severity of Illness Index; Zingiber officinale

Vancomycin (VAN) is a glycopeptide antibiotic which is active against gram positive bacteria including methicillin resistant Staphylococci. Free radicals are involved in the pathogenesis of vancomycin-induced nephrotoxicity. Therefore, the present study was conducted to investigate the antioxidant potential of curcumin (CUR) against the nephrotoxicity of vancomycin in male rats. Animals used in this study were divided into four groups; the first group was used as control, the second, third and fourth groups were treated orally with curcumin (200 mg/kg BW/day), vancomycin (200 mg/kg BW/day, i.p.), vancomycin plus curcumin, respectively. Curcumin was administered 2 weeks before and 1 week simultaneously with vancomycin. Results showed that thiobarbituric acid reactive substances (TBARS) in plasma and kidney tissue were significantly increased after vancomycin administration. While, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in plasma and kidney tissue and the content of glutathione (GSH) in kidney tissue were decreased compared to control. Vancomycin significantly increased the levels of urea and creatinine. The presence of curcumin with vancomycin caused reduction in induction levels of TBARS in plasma and kidney, urea and creatinine. It ameliorated vancomycin-induced decrease in the activities of antioxidant enzymes and GSH. The presence of curcumin with vancomycin alleviated its nephrotoxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize vancomycin nephrotoxicity.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Free Radicals; Kidney Diseases; Male; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Sprague-Dawley; Vancomycin

This study sought to investigate the modulatory effects of dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes on antioxidant status and renal damage induced by gentamycin in rats. Renal damage was induced in albino rats pretreated with dietary inclusion of ginger and turmeric (2% and 4%) by intraperitoneal (i.p.) administration of gentamycin (100 mg/kg body weight) for three days. Assays for renal damage biomarkers (plasma creatinine, plasma urea, blood urea nitrogen and plasma uric acid), malondialdehyde (MDA) content and reduced glutathione (GSH) content as well as renal antioxidant enzymes (catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were carried out. The study revealed significant (p < 0.05) increases in renal damage biomarkers following gentamycin administration with severe alteration in kidney antioxidant status. However, pretreatment with ginger and turmeric rhizome (2% and 4%) prior to gentamycin administration significantly (p < 0.05) protected the kidney and attenuated oxidative stress by modulating renal damage and antioxidant indices. This finding therefore suggests that dietary inclusion of ginger and turmeric rhizomes may protect against gentamycin-induced nephrotoxicity and oxidative stress.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Antioxidants; Blood Urea Nitrogen; Curcuma; Diet; Dose-Response Relationship, Drug; Gentamicins; Kidney Diseases; Male; Nigeria; Plant Extracts; Rats; Rats, Wistar; Weight Gain; Zingiber officinale

Renal ischemia followed by reperfusion results in kidney injury which in turn produces and releases destructive inflammatory cytokines into the circulation causing subsequent distant organ injury. Little data suggest the immune mechanism of curcumin on protection against ischemia/reperfusion induced injury. We investigated the immunomodulatory and anti-apoptotic effects of curcumin on ischemia/reperfusion (I/R) injury in rats. Thirty-six rats were randomly divided into three experimental groups (sham, I/R and curcumin pretreated I/R, n=12 each). Curcumin was administered orally to curcumin pretreated I/R group. Curcumin can significantly decrease both systemic as well as blood levels of cytokines (p<0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue level of TNF-α, IL-1β, IL-12, IL-18 and INF-γ that were increased by renal I/R injury (p<0.05). Curcumin pretreatment reduce pulmonary apoptotic pathway via significant inhibition of TGF-β and caspase-3 in kidney and lung tissues. Given that pulmonary apoptosis is an important complication of acute renal injury, we identified curcumin protective effect against distant organ I/R induced injury. Based on our results, we concluded that curcumin protects the kidneys and other vital organs against I/R injury via immune-mediated and the new identified anti-apoptotic mechanisms.

Topics: Animals; Apoptosis; Caspase 3; Curcumin; Cytokines; Immunologic Factors; Kidney; Kidney Diseases; Lung; Lung Injury; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Transforming Growth Factor beta

Generation of reactive oxygen species (ROS) is involved in the nephrotoxicity of platinum anticancer drugs. This study involved incubation of human embryonic kidney (HEK) 293 cells in cell culture media supplemented with cisplatin or oxaliplatin in the presence or absence of curcumin, a well-studied antioxidant. Thereafter several indices of oxidative stress have been measured, which included glutathione (GSH), total antioxidant capacity (TAC), and antioxidant enzymes [(superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX)]. The impact of platinum drugs on cells viability, lipid peroxidation, and lactate dehydrogenase leakage was also examined. The results show that at both acute (60 min) and chronic (24 h) durations of incubation, cisplatin and oxaliplatin induced oxidative stress as evidenced by significant inhibition of the activities of SOD, CAT, and GPX enzymes as well as significant reduction of the concentrations of GSH and TAC. Curcumin ameliorated the oxidative stress induced by these insults by significantly restoring the measured oxidative indices. Our findings provide evidence that curcumin significantly ameliorates oxidative stress induced by both cisplatin and oxaliplatin in HEK cells.

Topics: Antineoplastic Agents; Antioxidants; Cell Membrane; Cell Survival; Cisplatin; Curcumin; Drug Evaluation, Preclinical; Glutathione; HEK293 Cells; Humans; Kidney; Kidney Diseases; Organoplatinum Compounds; Oxaliplatin; Oxidative Stress; Phytotherapy

Acetaminophen is one of the most popular analgesic and antipyretic drugs and its overdose, which can cause severe damage to liver and kidneys, is one of the most common reasons of emergency admissions. In this study we investigated the effects of curcumin, derived from plant Curcuma longa, on acetaminophen toxicity, and the possibility of combining therapy of curcumin and N-acetyl cysteine (NAC) to treat this toxicity. The experiments were conducted on 72 male Sprague-Dawley rats randomly divided into 12 groups. Control group was left without treatment, and the other groups were treated with different combinations of acetaminophen, curcumin and NAC. 15min after intraperitoneal injection, the blood level of curcumin was measured using HPLC. Blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), blood urea nitrogen and creatinine were determined 18 and 42h after acetaminophen injection. One week later, the left kidney and the caudate lobe of the liver were harvested to assay glutathione peroxidase, catalase and malondialdehyde. The right kidney and the remaining lobes of the liver were used for histopathology. Analysis of organ function and oxidation parameters showed that curcumin significantly reduced toxic effects of acetaminophen on the liver and kidneys in a dose-dependent manner and significantly potentiated the protective effects of NAC. These findings were confirmed by histopathology. It is concluded that curcumin can protect the liver and kidney from the damage caused by acetaminophen overdose. Moreover, curcumin has the potential to be used in a combination therapy with NAC, significantly decreasing the therapeutic dose of NAC and therefore its side-effects.

Topics: Acetaminophen; Acetylcysteine; Animals; Biomarkers; Catalase; Curcumin; Drug Synergism; Glutathione Peroxidase; Kidney; Kidney Diseases; Liver; Liver Diseases; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; Serologic Tests

The rhizome of turmeric, Curcuma longa (CL), is a herbal medicine used in many traditional prescriptions. It has previously been shown that CL treatment showed greater than 47% recovery from cisplatin-induced cell damage in human kidney HEK 293 cells. This study was conducted to evaluate the recovery mechanisms of CL that occur during cisplatin induced nephrotoxicity by examining the genome wide mRNA expression profiles of HEK 293 -cells.. Recovery mechanisms of CL that occur during cisplatin-induced nephrotoxicity were determined by microarray, real-time PCR, immunofluorescent confocal microscopy and Western blot analysis.. The results of microarray analysis and real-time PCR revealed that NFκB pathway-related genes and apoptosis-related genes were down-regulated in CL-treated HEK 293 cells. In addition, immunofluorescent confocal microscopy and Western blot analysis revealed that NFκB p65 nuclear translocation was inhibited in CL-treated HEK 293 cells. Therefore, the mechanism responsible for the effects of CL on HEK 293 cells is closely associated with regulation of the NFκB pathway.. CL possesses novel therapeutic agents that can be used for the prevention or treatment of cisplatin-induced renal disorders.

Topics: Antineoplastic Agents; Cell Line; Cisplatin; Curcuma; Down-Regulation; Gene Expression Profiling; Genome; Humans; Kidney Diseases; Microarray Analysis; NF-kappa B; Plant Extracts; Polymerase Chain Reaction

Acetaminophen (APAP) can cause life-threatening renal damages and there is no specific treatment for APAP-induced renal damage. The aim of this study was to investigate the protective effects of curcumin (CMN) on APAP-induced nephrotoxicity. Nephrotoxicity was induced in male Wistar Albino rats by the administration of a single dose of 1000 mg/kg APAP intraperitoneally (i.p.). Some of these rats also received i.p. CMN (200mg/kg) at 30 min after the administration of APAP. Twenty-four hours after the administration of APAP, all the rats were sacrificed with a high dose of ketamine. Urea and creatinine levels were measured in the blood, and the levels of malondialdehyde (MDA) and glutathione (GSH), and antioxidant enzyme activity were determined in the renal tissue. Histopathological changes were studied. APAP administration caused elevated levels of renal MDA, and marked depletion of GSH levels and antioxidant enzyme activity, and deteriorated the renal functions as assessed by the increased plasma urea and creatinine levels as compared to control rats. CMN markedly reduced the elevated MDA levels, significantly increased the antioxidant enzyme activity and normalized the altered renal morphology in rats treated with APAP. CMN might be a potential candidate agent against APAP-induced nephrotoxicity, but further studies are required to identify this issue before clinical application becomes possible.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Catalase; Curcumin; Glutathione; Glutathione Peroxidase; Kidney Diseases; Male; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Superoxide Dismutase

The major component, called curcumin, of turmeric (Curcuma longa L.) (Family Zingiberaceae) powder is responsible for its biological actions. The present study aimed to prove the protective effect of turmeric extract against doxorubicin (DOX)-induced cardiac, hepatic, and renal toxicity as evaluated in rats. Body weight and urine volume of the animal groups under investigation were recorded daily throughout the experimental period. Also, the cardiac, hepatic, and renal toxicities were determined by estimating the changes in serum activities of the enzymes lactate dehydrogenase (LDH) and creatine kinase (CK), serum levels of alanine aminotransferase, aspartate aminotransferase, nitric oxide, albumin, and calcium, and kidney and liver tissue activities of superoxide dismutase and glutathione peroxidase, as well as the contents of glutathione and malondialdehyde. Hyperlipidemia was also determined, and protein and albumin changes in urine were estimated. Biochemical and histopathological findings demonstrate that turmeric extract has multiple therapeutic activities that are beneficially protective, and it has an ameliorative effect against DOX-induced cardiac toxicity and hepatotoxicity and blocks DOX-induced nephrosis. Similarly, turmeric extract inhibited the DOX-induced increase in plasma cholesterol, LDH, and CK. The present findings conclude that the turmeric extract has multiple therapeutic activities that block the cardiac, hepatic, and renal toxicities induced by DOX, and it also possibly acts as a free radical scavenger.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Calcium; Chemical and Drug Induced Liver Injury; Creatine Kinase; Curcuma; Curcumin; Doxorubicin; Drug-Related Side Effects and Adverse Reactions; Glutathione; Heart Diseases; Kidney Diseases; L-Lactate Dehydrogenase; Lipids; Male; Malondialdehyde; Nitric Oxide; Phytotherapy; Plant Extracts; Random Allocation; Rats; Serum Albumin; Transaminases; Troponin T

The influence of melatonin, curcumin, quercetin, and resveratrol pretreatment on ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage was studied. Male Wistar rats were treated orally once daily for 3 days with melatonin (10 mg/kg), curcumin (50 mg/kg), quercetin (15 mg/kg), and resveratrol (10 mg/kg). One hour after the last dose of antioxidants, a single dose of Fe-NTA was administered (8 mg of Fe/kg body weight, i.p.) to pre-treated animals. Twenty-four hours after Fe-NTA administration, the lipid peroxidation (LP), reduced glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-Px) were estimated in kidney homogenates. Iron, zinc, and copper concentrations were estimated in kidney tissue. Administration of Fe-NTA to rats induced renal LP (170%, P < 0.001) and inhibited catalase (78%, P < 0.05) in the kidney. The oral pretreatment with melatonin, curcumin, quercetin, and resveratrol each one was effective in decreasing the Fe-NTA-induced LP (P < 0.001); however, it did not influence the FeNTA-induced inhibition of renal CAT activity. No changes were found in renal GSH level and GSH-Px activity compared to control animals. The pretreatment with antioxidants did not affect the increase in renal iron content, blood urea nitrogen/creatinine ratio, and relative kidney weight of FeNTA-intoxicated rats. The results indicate that the pretreatment with natural antioxidants, curcumin, melatonin, quercetin, and resveratrol, significantly and equally suppressed lipid peroxidation induced by Fe-NTA but had no effect on other markers of FeNTA nephrotoxicity and iron deposition in kidneys.

Topics: Animals; Antioxidants; Blood Urea Nitrogen; Catalase; Curcumin; Disease Models, Animal; Ferric Compounds; Glutathione; Glutathione Peroxidase; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Melatonin; Metals, Heavy; Nitrilotriacetic Acid; Organ Size; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Resveratrol; Stilbenes

Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allograft. We investigated the effect of curcumin on ischemia-reperfusion (I/R) injury and the antioxidant effects of curcumin in rats.. Thirty rats were randomly divided into five experimental groups (control, sham, curcumin, I/R and I/R+curcumin, n=6 each). Curcumin was administered (200 mg kg(-1)) orally to curcumin and I/R+curcumin groups for 7 days. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, serum and tissue nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined. Histopathological examinations were also performed.. Curcumin significantly improved the urea and cystatin C levels in I/R+curcumin group compared to I/R group (p<0.05). Reduction of serum GSH-Px was significantly improved by curcumin (p<0.001), but SOD enzyme activity did not alter (p>0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue MDA, NO and PC and for tissue that were increased by renal I/R injury (p<0.001 for serum and p<0.05 for tissue, respectively). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney.. Based on our results, it can be concluded that curcumin protects the kidneys against I/R injury via its antioxidant effects.

Topics: Administration, Oral; Animals; Antioxidants; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Kidney; Kidney Diseases; Male; Rats; Rats, Wistar; Reperfusion Injury; Treatment Outcome

Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin-induced acute renal failure. Curcumin is claimed to be a potent anti-inflammatory and antioxidant agent. The present study was performed to explore the effect of curcumin against cisplatin-induced experimental nephrotoxicity. Curcumin in the dosages of 15, 30, and 60 mg kg(-1) was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance, and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. Systemic inflammation was assessed by tumor necrosis factor-alpha (TNF-alpha) levels. A single dose of cisplatin resulted in marked inflammation (486% rise in TNF-alpha level) and oxidative stress and significantly deranged renal functions as well as renal morphology. The serum TNF-alpha level was markedly reduced in curcumin-treated rats. Curcumin treatment significantly and dose-dependently restored renal function, reduced lipid peroxidation, and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. The present study demonstrates that curcumin has a protective effect on cisplatin-induced experimental nephrotoxicity, and this effect is attributed to its direct anti-inflammatory and strong antioxidant profile. Hence, curcumin has a strong potential to be used as a therapeutic adjuvant in cisplatin nephrotoxicity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cisplatin; Curcumin; Inflammation; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The present investigation reports the effect of curcumin, an antioxidant, on gentamicin-induced-renal oxidative damage in rats. Curcumin (200 mg/kg p.o.) was administered for 2 weeks before and 1 week simultaneously with gentamicin (100 mg/kg i.p.). Saline treated rats served as control. Serum creatinine, blood urea (BUN), urinary protein, glucose, urine gamma glutamyl transferase and urine volume increased in rats treated with gentamicin while creatinine clearance decreased compared to controls P<0.001. Renal histological examination revealed tubular necrosis. Curcumin significantly normalized the above parameters. Gentamicin decreased the activities of catalase (CAT), gutathione peroxidase (GSHPx) and the level of glutathione (GSH) but the activity of copper, zinc-superoxide dismutase (Cu, Zn-SOD) was unaltered compared to control. Curcumin attenuated the gentamicin-induced reduction in the activities of CAT, GSHPx and level of GSH by 31%, 55% and 74%, respectively. Curcumin attenuated the gentamicin-induced increases in both plasma malondialdehyde (MDA) and kidney MDA by 57% and 62%, respectively, as well as lipid hydroperoxide (LOOH) formation by 52% and 56% in rat plasma and kidney, respectively. However, Curcumin did not reduce gentamicin-induced formation of LOOH, both in the plasma and kidney, in the presence of exogenous oxidants (1 mM FeSO4, 1 mM ascorbate, 0.2 mM H2O2). Our data indicate that the natural antioxidant curcumin can be a potent protective agent against renal oxidative damage mediated by gentamicin.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Antioxidants; Curcumin; Disease Models, Animal; Drug Antagonism; Drug Therapy, Combination; Enzymes; Gentamicins; Injections, Intraperitoneal; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Tubules; Male; Necrosis; Oxidative Stress; Rats; Rats, Wistar

In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates.. CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology.. In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cyclosporine; Female; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Function Tests; Male; Oxidative Stress; Rats; Rats, Wistar

The present study investigated the effect of curcumin on adriamycin (ADR) nephrosis in rats. The results indicate that ADR-induced kidney injury was remarkably prevented by treatment with curcumin. Treatment with curcumin markedly protected against ADR-induced proteinuria, albuminuria, hypoalbuminaemia and hyperlipidaemia. Similarly, curcumin inhibited ADR-induced increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (a marker of renal tubular injury), fibronectin and glycosaminoglycan and plasma cholesterol. Curcumin restored renal function in ADR rats, as judged by the increase in GFR. The data also demonstrated that curcumin protected against ADR-induced renal injury by suppressing oxidative stress and increasing kidney glutathione content and glutathione peroxidase activity. In like manner, curcumin abolished ADR-stimulated kidney microsomal and mitochondrial lipid peroxidation. These data suggest that administration of curcumin is a promising approach in the treatment of nephrosis caused by ADR.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibiotics, Antineoplastic; Body Weight; Curcumin; Doxorubicin; Glomerular Filtration Rate; Kidney Diseases; Lipid Peroxidation; Male; Microsomes; Mitochondria; Proteinuria; Rats; Rats, Wistar

Ureteral obstruction results in an injury response that can progress to irreversible renal fibrosis and tubular atrophy by apoptosis. The molecular events leading to apoptosis from obstruction are not well understood. We investigated the effect of bioflavonoids and angiotensin II inhibition on apoptotic and inflammatory gene expression in a model of unilateral ureteral obstruction (UUO).. Complete UUO was produced in rats by ureteral ligation. The rats were treated with dimethyl sulfoxide (control), enalapril, losartan, curcumin, or quercetin. The animals were killed on day 7 and both obstructed and contralateral unobstructed kidneys were harvested. Expression of the inflammatory chemokine monocyte chemotactic protein-1, apoptosis effector genes Fas and Fas ligand, and oxidative stress gene HO-1 was evaluated by reverse transcriptase-polymerase chain reaction.. Ureteral obstruction was associated with a 6.3-fold increase in monocyte chemotactic protein-1 expression compared with sham-operated rats (P = 0.01). Monocyte chemotactic protein-1 expression was severely attenuated in all other treatment groups (P <0.05). Similarly, Fas and Fas ligand expression were increased in control UUO kidneys compared with sham-operated ones (P <0.05). Fas gene expression was significantly inhibited by quercetin but not enalapril, losartan, or curcumin compared with the control. The induction of Fas ligand was attenuated in all treatment groups (P <0.05). HO-1 was expressed at low levels in both unobstructed and obstructed kidneys. Treatment with curcumin increased HO-1 expression fourfold (P <0.05).. The expression of apoptotic and chemokine genes is significantly upregulated in UUO. Bioflavonoids and angiotensin inhibitors are able to attenuate the expression of these genes and thus may be beneficial in renal protection.

Topics: Angiotensin II; Animals; Apoptosis; Chemokines; Curcumin; Disease Models, Animal; Flavonoids; Gene Expression; Kidney Diseases; Male; Nephritis; Quercetin; Rats; Rats, Sprague-Dawley; Ureteral Obstruction