curcumin and Nephritis

Acute kidney injury (AKI) is a common kidney disease with a high risk of death and can develop into chronic kidney disease (CKD) and renal failure eventually. Curcumin, an herbal supplement, has been reported exhibiting a renoprotective role in AKI. However, the underlying mechanism is largely unclear.. Recent research showed that Mincle (Macrophage-inducible C-type lectin) maintained M1 macrophage polarization, which plays a key role in kidney injury of AKI through up-regulating the expression and secretion of inflammatory cytokines. Here, we investigated the effects of Curcumin on Mincle expression and macrophage polarization in vitro using lipopolysaccharide (LPS) induced macrophage inflammatory cell model and in vivo using a cisplatin induced murine AKI (cis-AKI) model.. Cell activation, inflammatory cytokines expression and secretion, protein levels, macrophage polarization and renal pathology were analyzed.. Our results showed that Curcumin markedly reduced the mRNA expression and secretion of IL-1β, IL-6, TNFα and MCP-1 in LPS stimulated RAW264.7 cell and the supernatant. The same results were found in Curcumin treated cis-AKI kidney and blood. The data also demonstrated that Curcumin remarkably down-regulated mRNA expression and protein level of Mincle in cis-AKI kidney and also reduced expression of iNOS (M1 macrophage marker) as well as inhibited the activation of Syk and NF-kB. Interestingly, although Mincle deletion in RAW264.7 cell largely decreased the LPS-induced protein level of iNOS, Curcumin cannot further reduce expression of iNOS without Mincle, indicating that Curcumin inhibits M1 macrophage with a Mincle-dependent pattern. Furthermore, flow cytometry results showed that Curcumin significantly decreased the iNOS positive macrophages and increased the CD206 (M2 macrophage marker) positive macrophages in vivo and in vitro.. Our findings prove that Curcumin protects kidney from cisplatin induced AKI through inhibiting Mincle maintained M1 macrophage phenotype, that may provide a specific renoprotection mechanism for Curcumin to develop it as a new therapeutic candidate for AKI.

Topics: Acute Kidney Injury; Animals; Cisplatin; Curcumin; Cytokines; Down-Regulation; Kidney; Lectins, C-Type; Lipopolysaccharides; Macrophages; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Nephritis; NF-kappa B; Phenotype; RAW 264.7 Cells; Up-Regulation

Nephrolithiasis is one of the most common and frequent urologic diseases worldwide. Several pathophysiological mechanisms are involved in stone formation, including oxidative stress, inflammation, apoptosis, fibrosis and autophagy. Curcumin, the predominant active component of turmeric, has been shown to have pleiotropic biological and pharmacological properties, such as antioxidant, anti-inflammatory and antifibrotic effects.. The current study proposed to systematically investigate the protective effects and the underlying mechanisms of curcumin in a calcium oxalate (CaOx) nephrolithiasis mouse model.. The animal model was established in male C57BL/6 mice by successive intraperitoneal injection of glyoxylate (100 mg/kg) for 1 week. Curcumin was orally given to mice 7 days before the injection of glyoxylate and for a total of 14 days at 50 mg/kg or 100 mg/kg. Bilateral renal tissue was harvested and processed for oxidative stress index detection, histopathological examinations and other analyses.. Coadministration of curcumin could significantly reduce glyoxylate-induced CaOx deposition and simultaneous tissue injury in mouse kidneys. Meanwhile, curcumin alleviated the oxidative stress response via reducing MDA content and increasing SOD, CAT, GPx, GR and GSH levels in this animal model. Moreover, treatment with curcumin significantly inhibited apoptosis and autophagy induced by hyperoxaluria. Curcumin also attenuated the high expression of IL-6, MCP-1, OPN, CD44, α-SMA, Collagen I and collagen fibril deposition, which were elevated by hyperoxaluria. Furthermore, the results revealed that both the total expression and nuclear accumulation of Nrf2, as well as its main downstream products such as HO-1, NQO1 and UGT, were decreased in the kidneys of mice in the crystal group, while treatment with curcumin could rescue this deterioration.. Curcumin could significantly alleviate CaOx crystal deposition in the mouse kidney and the concurrent renal tissue injury. The underlying mechanism involved the combination of antioxidant, anti-apoptotic, inhibiting autophagy, anti-inflammatory, and antifibrotic activity and the ability to decrease expression of OPN and CD44 through the Nrf2 signaling pathway. The pleiotropic antilithic properties, combined with the minimal side effects, make curcumin a good potential choice to prevent and treat new or recurrent nephrolithiasis.

Topics: Animals; Apoptosis; Autophagy; Calcium Oxalate; Curcumin; Disease Models, Animal; Fibrosis; Glyoxylates; Hyaluronan Receptors; Kidney; Male; Mice, Inbred C57BL; Nephritis; Nephrolithiasis; Osteopontin; Oxidative Stress; Protective Agents; Signal Transduction

Gentamicin-induced nephrotoxicity is one of the most common causes of acute kidney injury (AKI). The phenotypic alterations that contribute to acute kidney injury include inflammatory response and oxidative stress. Curcumin has a wide range biological functions, especially as an antioxidant. This study was designed to evaluate the renoprotective effects of curcumin treatment in gentamicin-induced AKI.. Gentamicin-induced AKI was established in female Sprague-Dawley rats. Rats were treated with curcumin (100 mg/kg body mass) by intragastric administration, once daily, followed with an intraperitoneal injection of gentamicin sulfate solution at a dose of 80 mg/kg body mass for 8 consecutive days. At days 3 and 8, the rats were sacrificed, and the kidneys and blood samples were collected for further analysis.. The animals treated with gentamicin showed marked deterioration of renal function, together with higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the plasma as compared with the controls. Animals that underwent intermittent treatment with curcumin exhibited significant improvements in renal functional parameters. We also observed that treatment with curcumin significantly attenuated renal tubular damage, apoptosis, and oxidative stress. Curcumin treatment exerted anti-apoptosis and anti-oxidative effects by up-regulating Nrf2/HO-1 and Sirt1 expression.. Our data clearly demonstrate that curcumin protects kidney from gentamicin-induced AKI via the amelioration of oxidative stress and apoptosis of renal tubular cells, thus providing hope for the amelioration of gentamicin-induced nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Cell Adhesion Molecules; Curcumin; Female; Gene Expression Regulation; Gentamicins; Kidney; Kidney Tubules; Lipocalin-2; Lipocalins; Nephritis; NF-E2-Related Factor 2; Oxidative Stress; Random Allocation; Rats, Sprague-Dawley; Sirtuin 1

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

Acute or chronic kidney inflammation is closely related to the progress of kidney diseases. Curcumin, a yellow pigment present in the rhizome of turmeric (Curcuma longa L. Zingiberaceae), was found to be a potential anti-inflammatory agent. The present study aimed to investigate the effects and explore the protective mechanism of curcumin on lipopolysaccharide (LPS)-induced kidney inflammation in mice using gene chip and pathological technology. Nine SPF Kunming mice (aged 6-8 weeks, weighing 20-25 g) were divided into three groups. Saline and LPS were injected intraperitoneally in a normal control group and a model group, respectively. Mice in the treatment group were first injected with curcumin (5 mg/kg) for 3 days before being injected with LPS (5 mg/kg). Kidney tissues were harvested at 6 h after treatment. Parts of kidney were fixed with 10 % formaldehyde for HE, Periodic acid-Schiff staining, and immunohistochemistry. Affymetrix gene chips (mouse 430 chip) were used to detect the renal gene expression profile, and the results were analyzed using bioinformatics methods. The renal gene expression profile showed that there are 148 Affy IDs (up-down group) whose levels of gene expression were increased after LPS stimulation and decreased by curcumin treatment and that there are 133 Affy IDs (down-up group) exhibiting the opposite trend. In the differentially expressed genes of the up-down group, 21 Gene Ontology (GO) genes were selected by screening function (P ≤ 0.01). In the biological processes, most of the genes were found to be related to the genes of regulation of macrophage activation and macrophage activation-associated genes. In the cellular localization, there were four functional GO genes (P ≤ 0.01); in the molecular structure, there were seven functional GO genes (P ≤ 0.01). In the down-up group, there were functional GO genes (P ≤ 0.01) and one functional GO gene (P ≤ 0.01) in the biological process and the cellular localization, respectively. Macrophage infiltration could be observed as early as 6 h after LPS stimulation. Pretreatment with 5 mg/kg of curcumin significantly decreased the macrophage infiltration. At 6 h after LPS injection, significant decreased expression of M6PRBP-1 and NEDD-4 was observed in renal tissue. On the other hand, pretreatment with curcumin significantly increased renal M6PRBP-1 and NEDD-4 expression. In this study, we also found the signaling pathway and the possible target gene of the protective effects of cu

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrier Proteins; Curcumin; Endosomal Sorting Complexes Required for Transport; Gene Expression; Gene Expression Profiling; Kidney; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Nedd4 Ubiquitin Protein Ligases; Nephritis; Perilipin-3; Ubiquitin-Protein Ligases

Renal inflammation is the main pathological change in many acute and chronic kidney diseases. Curcumin, a yellow pigment present in the rhizome of turmeric (Curcuma longa L. Zingiberaceae), was found to be a potential anti-inflammatory agent. The present study aimed to investigate the effects of curcumin on the inflammation of mice kidney and cultured renal tubular epithelial cells (HK-2 cells) induced by lipopolysaccharide (LPS) and to explore the mechanism. Curcumin was injected intraperitoneally before LPS administration. Renal inflammation was assessed by evaluating monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration in renal tissue using immunohistochemical methods, and also by measuring renal MCP-1 mRNA level using Real-Time polymerase chain reaction (PCR). HK-2 cells were cultured to investigate the in vitro effect of curcumin against LPS-induced renal inflammation. The expression of MCP-1 and interleukin-8 (IL-8) mRNA was measured by Real-Time PCR. The expression of MCP-1 and IL-8 protein in supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The activity of nuclear factor (NF)-κB was detected by electrophoretic mobility shift assay (EMSA). The results demonstrated that curcumin could inhibit LPS-induced renal MCP-1 mRNA expression. Curcumin also significantly inhibited the expression of MCP-1 and IL-2 mRNA in HK-2 cells, and partially inhibited the secretion of MCP-1 and IL-8. Furthermore, curcumin was found to inhibit the DNA-binding activity of NF-κB. The present study demonstrated that curcumin has a protective effect on LPS-induced experimental renal inflammation, and this effect might be attributed to its inhibitory effects on MCP-1 mRNA expression and DNA-binding activity of NF-κB. Hence, curcumin might be potentially useful in some kidney diseases by preventing renal inflammation.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Chemokine CCL2; Curcuma; Curcumin; Epithelial Cells; Humans; Interleukin-2; Interleukin-8; Lipopolysaccharides; Mice; Mice, Inbred Strains; Nephritis; NF-kappa B; Phytotherapy; Plant Extracts; Polymerase Chain Reaction; Rhizome; RNA, Messenger

TNF-alpha and NF-kappaB play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic cells, curcumin is shown to antagonize TNF-alpha-elicited NF-kappaB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared with enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague-Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin-treated (curcumin), and enalapril-treated (enalapril) groups. Sham-operated animals served as a control. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared with the control, the Nx animals had significantly higher plasma and kidney TNF-alpha, which was associated with NF-kappaB activation and macrophage infiltration in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARgamma) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF-alpha. Curcumin dose dependently antagonized the TNF-alpha-mediated decrease in PPARgamma and blocked transactivation of NF-kappaB and repression of PPARgamma, indicating that the anti-inflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Blood Urea Nitrogen; Cells, Cultured; Creatinine; Curcumin; Disease Models, Animal; Enalapril; Hypertension, Renal; Kidney Failure, Chronic; Macrophages; Mesangial Cells; Nephrectomy; Nephritis; NF-kappa B; PPAR gamma; Proteinuria; Rats; Rats, Sprague-Dawley; Transfection; Tumor Necrosis Factor-alpha

Tetrahydrocurcumin is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of tetrahydrocurcumin and curcumin against chloroquine-induced nephrotoxicity were studied in female wistar rats. Oral administration of tetrahydrocurcumin significantly prevented the occurrence of chloroquine (970 mg/kg body weight)-induced renal damage. Upon administration of tetrahydrocurcumin to chloroquine-treated rats, the level of lipid peroxidation was significantly decreased while the levels of non-enzymic and enzymic antioxidants were significantly increased in kidney. Oral administration (80 mg/kg body weight) attenuated the chloroquine-induced nephrotoxicity by significantly decreased levels of serum urea and creatinine with significant normalization of creatinine clearance. On administration of tetrahydrocurcumin, the depleted renal antioxidant defense system (enzymatic and non-enzymatic antioxidants) was significantly increased in rats treated with chloroquine. These biochemical observations were supplemented by histopathological examination of kidney section. These results suggest that administration of chloroquine imposes an oxidative stress to renal tissue and that tetrahydrocurcumin protects the oxidative damage associated with chloroquine.

Topics: Administration, Oral; Animals; Antioxidants; Chemoprevention; Chloroquine; Creatinine; Curcumin; Disease Models, Animal; Female; Kidney; Lipid Peroxidation; Nephritis; Oxidative Stress; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Urea

To observe whether curcumin could inhibit the accumulation of the collagen IV and fibronectin in the glomeruli in nephrotoxi sera nephritis rats.. Seventy-two healthy male Sprague-Dawley rats were divided into three groups, with 24 animals in each group. For normal control group, normal saline (0.5 ml/d) was injected through intra-caudal-vein for two days, and at the same time normal saline (0.5 ml/kg) was also daily administered intraperitoneally. For nephrotoxic sera nephritis group, nephrotoxic sera (0.5 ml/d) was injected through the tail vein for two days and dimethyl sulfoxide (0.5 ml/kg) was given intraperitoneally daily. For curcumin group, nephrotoxic sera was injected as above and meanwhile curcumin (50 mg.kg(-1).d(-1)) was administered intraperitoneally every day. Six rats in each group were killed on the 3rd, 7th, 14th and 28th day. Their renal tissue was fixed in 10% formalin for examining the expression of collagen IV and fibronectin.. Minimal staining of collagen IV and fibronectin was detected in the basement membrane of normal control rats glomeruli. In the nephrotoxic sera nephritis rats and curcumin treated nephrotoxic sera nephritis rats, the accumulation of collagen IV and fibronectin was increased progressively, with significant difference in the accumulation of collagen IV (P<0.01) between these two groups at the same time points, while the significant difference in fibronectin accumulation (P<0.05) appeared only after the 7th days.. Curcumin can reduce the accumulation of collagen IV and fibronectin in the glomeruli. Hence we postulated that curcumin might have beneficial effect for retarding glomerulosclerosis.

Topics: Animals; Collagen Type IV; Curcumin; Extracellular Matrix; Fibronectins; Kidney Glomerulus; Male; Nephritis; Rats; Rats, Sprague-Dawley

Chronic renal allograft nephropathy is associated with both immune and ischemic injury which may act synergistically to promote an inflammatory response. The immunosuppressant mycophenolic acid and the polyphenolic agents curcumin and quercetin possess properties that might ameliorate such injury. We studied the effects of these agents in models of ischemic renal injury and skin allograft rejection.. Ischemic acute tubular necrosis was produced in rats by renal pedicle occlusion with contralateral nephrectomy. Animals were treated with mycophenolic acid, quercetin and curcumin, or a combination of agents. Animals were killed on days 2 and 7 after operation and tissue samples were collected. Renal tubular apoptosis and cellular proliferation were assessed by immunohistochemistry. Expression of the cytokines RANTES and AIF were evaluated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).. Treatment with the polyphenolic compounds alone or in combination with mycophenolic acid was associated with less tubular damage, attenuation of renal inflammation, and prolongation of skin graft survival. A combination of agents decreased serum creatinine on day 2 from 4.5 to 0.9 mg./dl. (p< or =0.01) and at day 7 from 3.8 to 0.6 mg./dl. (p< or =0.01). Treatment with the polyphenolic compounds inhibited apoptosis at day 2. By RT-PCR, RANTES and AIF were detected at high levels on days 2 and 7. Treatment with these agents alone or in combination strongly attenuated this increased expression.. The combination of mycophenolic acid with curcumin and quercetin reduces renal injury and facilitates repair. These agents may have a role in therapeutic regimens that are both immunosuppressive and renoprotective.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemokine CCL5; Curcumin; Gene Expression Regulation; Graft Rejection; Immunohistochemistry; Immunosuppressive Agents; Ischemia; Kidney; Male; Mycophenolic Acid; Nephritis; Quercetin; Rats; Rats, Sprague-Dawley; Skin Transplantation

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