curcumin and Renal-Insufficiency

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.

Topics: Animals; Antioxidants; Curcumin; Humans; Renal Insufficiency

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

Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)-treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU-induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU-induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU-induced nephrotoxicity.

Topics: Animals; Antioxidants; Curcumin; Fluorouracil; Glutathione; Hesperidin; Humans; Kidney; Malondialdehyde; Mice; Oxidative Stress; Renal Insufficiency; Superoxide Dismutase

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

Doxorubicin (DXR) is one of the most important chemotherapeutic agent. However, nephrotoxicity reduces its clinical utility in humans. The aim of the study was to investigate protective effects of curcumin (CMN) against DXR-induced nephrotoxicity. Rats were subjected to oral treatment of CMN (100 and 200 mg/kg body weight) for 7 days. Nephrotoxicity was induced by single intra peritoneal injection of DXR (40 mg/kg body weight) on the fifth day and then the experiment was terminated on the eighth day. Nephroprotective effects of CMN were associated with decrease in serum toxicity markers and increase in antioxidant enzyme activities. CMN was able to reduced the levels of inflammatory markers such as TNF-α, NF-κB, IL-1β, iNOS and COX-2 in the rats. It also reduced the expressions of apoptotic marker including caspase-3, and oxidative DNA damage marker including 8-OHdG. Collectively, these findings indicated that CMN protect against DXR-induced nephrotoxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibiotics, Antineoplastic; Antioxidants; Apoptosis; Biomarkers; Curcumin; Cyclooxygenase 2; DNA Damage; Dose-Response Relationship, Drug; Doxorubicin; Kidney; Lipid Peroxidation; Male; Nitric Oxide Synthase Type II; Oxidation-Reduction; Oxidative Stress; Protective Agents; Random Allocation; Rats, Wistar; Renal Insufficiency; Topoisomerase II Inhibitors

The molecular mechanism of curcumin in macrophage polarization remains unknown in renal failure. We examined, whether curcumin treatment is associated with the modulation of renal function and macrophage phenotype switch in daunorubicin (DNR) induced nephrotoxicity model. Sprague-Dawley rats were treated with a cumulative dose of 9mg/kg DNR (i.v). Followed by curcumin (100mg/kg) administration orally every day for 6weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was assessed by measuring creatinine and blood urea nitrogen in serum. These changes were reversed by treatment with curcumin, which resulted in significant improvement in renal function. Furthermore, curcumin increased cluster of differentiation (CD)163 expression, and down-regulated renal expression of antigen II type I receptor (AT1R), endothelin (ET)1, ET receptor type A and B (ETAR and ETBR), CD68 and CD80. Renal protein expression of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)κB p65 were increased in DNR treated rats, and treatment with curcumin attenuated these increased expression. Curcumin mediated a further increase in the levels of interleukin (IL)-10. In addition, the expression of M1 phenotype was increased in DNR treated rats, which were attenuated by curcumin. Taken together, our results demonstrated that polyphenol curcumin has an ability to improve renal function and might induce the phenotypic switching from M1 to M2 macrophage polarization in DNR induced nephrotoxicity in rats.

Topics: Animals; Blood Urea Nitrogen; Creatinine; Curcumin; Daunorubicin; Down-Regulation; Inflammation; Interleukin-10; Kidney; Kidney Function Tests; Macrophages; Male; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Tetraspanin 30

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham operated animals on normal diet (control) and WD (WD). To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin (PM), a known LPS antagonist, and curcumin (CU), a compound known to ameliorate chronic kidney disease (CKD), was given to Nx animals on western diet (Nx+WD+PM and Nx+WD+CU, respectively). Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.

Topics: Animals; Atherosclerosis; Cholesterol; Curcumin; Diet, High-Fat; Diet, Western; Dietary Fats; Disease Models, Animal; Gene Expression; Glucose Intolerance; Hyperglycemia; Intestinal Mucosa; Intestines; Kidney; Lipopolysaccharides; Macrophages; Mice; Mice, Knockout; Nephrectomy; Polymyxins; Receptors, LDL; Renal Insufficiency

Previously, we showed that curcumin prevents chronic kidney disease (CKD) development in ⅚ nephrectomized (Nx) rats when given within 1 wk after Nx (Ghosh SS, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, Fakhry I, Gehr TW. Am J Physiol Renal Physiol 296: F1146-F1157, 2009). To better mimic the scenario for renal disease in humans, we began curcumin and enalapril therapy when proteinuria was already established. We hypothesized that curcumin, by blocking the inflammatory mediators TNF-α and IL-1β, could also reduce cyclooxygenase (COX) and phospholipase expression in the kidney. Nx animals were divided into untreated Nx, curcumin-treated, and enalapril-treated groups. Curcumin (75 mg/kg) and enalapril (10 mg/kg) were administered for 10 wk. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was comparably reduced by curcumin and enalapril, with only enalapril significantly lowering blood pressure. Compared with controls, Nx animals had higher plasma/kidney TNF-α and IL-1β, which were reduced by curcumin and enalapril treatment. Nx animals had significantly elevated kidney levels of cytosolic PLA(2), calcium-independent intracellular PLA(2), COX 1, and COX 2, which were comparably reduced by curcumin and enalapril. Studies in mesangial cells and macrophages were carried out to establish that the in vivo increase in PLA(2) and COX were mediated by TNF-α and IL-1β and that curcumin, by antagonizing the cytokines, could significantly reduce both PLA(2) and COX. We conclude that curcumin ameliorates CKD by blocking inflammatory signals even if it is given at a later stage of the disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Curcumin; Enalapril; Inflammation; Inflammation Mediators; Interleukin-1beta; Kidney; Nephrectomy; Phospholipases; Prostaglandin-Endoperoxide Synthases; Rats; Renal Insufficiency; Tumor Necrosis Factor-alpha

Autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in either the PKD1 or PKD2 gene is a major cause of end-stage renal failure. A number of compounds targeting specific signaling pathways were able to inhibit cystogenesis in rodent models and are currently being tested in clinical trials. However, given the complex signaling in ADPKD, an ideal therapy would likely have to comprise several pathways at once. Therefore, multitarget compounds may provide promising therapeutic interventions for the treatment of ADPKD. To test this hypothesis, we treated Pkd1-deletion mice with diferuloylmethane (curcumin), a compound without appreciable side effects and known to modulate several pathways that are also altered in ADPKD, e.g., mammalian target of rapamycin (mTOR) and Wnt signaling. After conditional inactivation of Pkd1, mTOR signaling was indeed elevated in cystic kidneys. Interestingly, also activation of signal transducers and activator of transcription 3 (STAT3) strongly correlated with cyst progression. Both pathways were effectively inhibited in vitro by curcumin. Importantly, Pkd1-deletion mice that were treated with curcumin and killed at an early stage of PKD displayed improved renal histology and reduced STAT3 activation, proliferation index, cystic index, and kidney weight/body weight ratios. In addition, renal failure was significantly postponed in mice with severe PKD. These data suggest that multitarget compounds hold promising potential for safe and effective treatment of ADPKD.

Topics: Animals; Cell Proliferation; Cells, Cultured; Curcumin; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Kidney; Mice; Mice, Knockout; Organ Size; Phosphorylation; Polycystic Kidney, Autosomal Dominant; Renal Insufficiency; Ribosomal Protein S6; Signal Transduction; STAT3 Transcription Factor; TOR Serine-Threonine Kinases; TRPP Cation Channels

We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium [Cr(VI)] compound potassium dichromate (K(2)Cr(2)O(7)) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400 mg/kg bw 10 days before and 2 days after K(2)Cr(2)O(7) injection), (2) pretreatment (400 mg/kg bw for 10 days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400 mg/kg bw 2 days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48 h later after a single K(2)Cr(2)O(7) injection (15 mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysfunction, histological damage, oxidant stress, and the decrease in antioxidant enzyme activity both in kidney tissue and in mitochondria. Curcumin pretreatment attenuated K(2)Cr(2)O(7)-induced mitochondrial dysfunction (alterations in oxygen consumption, ATP content, calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II-III, and V) but was unable to modify renal and mitochondrial Cr(VI) content or to chelate chromium. Curcumin posttreatment was unable to prevent K(2)Cr(2)O(7)-induced renal dysfunction. In further experiments performed in curcumin (400 mg/kg)-pretreated rats it was found that this antioxidant accumulated in kidney and activated Nrf2 at the time when K(2)Cr(2)O(7) was injected, suggesting that both direct and indirect antioxidant effects are involved in the protective effects of curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of curcumin pretreatment against K(2)Cr(2)O(7)-induced renal oxidant damage.

Topics: Animals; Antioxidants; Carcinogens, Environmental; Chromium; Curcumin; Kidney; Lipid Peroxidation; Male; Mitochondria; NF-E2-Related Factor 2; Oxidative Stress; Oxygen Consumption; Rats; Rats, Wistar; Renal Insufficiency

This study aimed to investigate the possible protective role of curcumin against renal damage caused by administration of cyclosporine A (CsA) in adult male rats. For this purpose, 27 adult male albino rats were used and divided into three equal groups. Group I (control group) and group II (CsA-treated group) received a daily subcutaneous injection of CsA at a dose of 20 mg/kg b.w. Group III (prophylactic group) received a daily oral curcumin at a dose of 15 mg/kg b.w. simultaneously with CsA. After 21 days, all the animals were anaesthetized and the kidneys were rapidly removed and processed to prepare paraffin sections stained with H&E, PAS and Masson's trichrome. In addition, the glutathione S-transferase (GST) enzyme was detected immunohistochemically. The optical density and the area (in %) of positive GST immunoreactions were measured in the cytoplasm of renal tubules and glomeruli and the data were statistically analyzed. Examination of sections from CsA-treated group showed renal tubules with vacuolated cytoplasm and others with darkly stained pyknotic nuclei. Apical brush borders of proximal tubules were undefined and PAS positive granules were noticed in their cytoplasm. The renal corpuscles contained shrunken glomeruli with widening of their Bowman's spaces. Inflammatory cellular infiltrate and increase in the collagen fibers were observed between the renal tubules. In prophylactic group, the structure of renal tubules and corpuscles were preserved except few tubular darkly stained pyknotic nuclei. Numerous blood vessels, few cellular infiltration and thin collagen fibers were observed between the renal tubules. Statistical analysis of morphometric data showed significant increase in the optical density of GST immunoreactivity in the cells of renal tubules and glomeruli of CsA-treated group when compared with the control or prophylactic groups. However, a significant decrease in the area of GST immunoreactivity in sections from prophylactic group was observed when compared with control or CsA-treated groups. In conclusion, protective effect of curcumin against cyclosporine-induced nephrotoxicity in rats was proven based on the study of histological changes and GST immunoexpression. This study supposes the possible therapeutic applications of curcumin in CsA-treated patients.

Topics: Animals; Curcumin; Cyclosporine; Kidney; Male; Rats; Renal Insufficiency