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Soetikno V., Watanabe K., Sari F.R., Harima M., Thandavarayan R.A., Veeraveedu P.T., Arozal W., Sukumaran V., Lakshmanan A.P., Arumugam S., Suzuki K.
36769252100;55492737200;36455410900;34971238300;23390800400;12796732500;32067462200;35070365600;36673278300;38860956300;55624483910;
Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats
2011
Molecular Nutrition and Food Research
55
11
1655
1665
89
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Department of Pharmacology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Soetikno, V., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan, Department of Pharmacology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Watanabe, K., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Sari, F.R., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Harima, M., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Thandavarayan, R.A., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Veeraveedu, P.T., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Arozal, W., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Sukumaran, V., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Lakshmanan, A.P., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Arumugam, S., Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan; Suzuki, K., Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100mg/kg/day, p.o., for 8wk. At 11wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Curcumin; Diabetic nephropathy; Mitogen-activated protein kinase; Oxidative stress; Protein kinase C
antioxidant; curcumin; isoenzyme; messenger RNA; neutrophil cytosol factor 67K; Nox4 protein, rat; phosphoprotein; protein kinase C; protein kinase C alpha; protein kinase C beta; protein kinase inhibitor; reduced nicotinamide adenine dinucleotide phosphate oxidase; scleroprotein; streptozocin; animal; article; diabetic nephropathy; drug antagonism; drug effect; gene expression regulation; genetics; insulin dependent diabetes mellitus; kidney; male; metabolism; oxidative stress; pathology; pathophysiology; randomization; rat; signal transduction; Sprague Dawley rat; Animals; Antioxidants; Curcumin; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Extracellular Matrix Proteins; Gene Expression Regulation; Isoenzymes; Kidney; Male; MAP Kinase Signaling System; NADPH Oxidase; Oxidative Stre
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