Abstract
Previous investigations have demonstrated that green tea polyphenols and partially hydrolyzed guar gum as dietary fiber have antioxidative and hypolipidemic activity, respectively, supporting their reduction of risk factors in the course of diabetic nephropathy via a hypoglycemic effect and ameliorating the decline of renal function through their combined administration to rats with subtotal nephrectomy plus streptozotocin (STZ) injection. As a further study, we examined whether (-)-epigallocatechin 3-O-gallate (EGCg), the main polyphenolic compound, could ameliorate the development of diabetic nephropathy. Rats with subtotal nephrectomy plus STZ injection were orally administrated EGCg at doses of 25, 50, and 100 mg/kg body weight/day. After a 50-day administration period, EGCg-treated groups showed suppressed hyperglycemia, proteinuria, and lipid peroxidation, although there were only weak effects on the levels of serum creatinine and glycosylated protein. Furthermore, EGCg reduced renal advanced glycation end-product accumulation and its related protein expression in the kidney cortex as well as associated pathological conditions. These results suggest that EGCg ameliorates glucose toxicity and renal injury, thus alleviating renal damage caused by abnormal glucose metabolism-associated oxidative stress involved in renal lesions of diabetic nephropathy.
Footnotes
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.107029.
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ABBREVIATIONS: STZ, streptozotocin; EGCg, (-)-epigallocatechin 3-O-gallate; Cr, creatinine; TBA, thiobarbituric acid; BSA, bovine serum albumin; PAGE, polyacrylamide gel electrophoresis; iNOS, inducible nitric-oxide synthesis; COX, cyclooxygenase; NF-κB, nuclear factor-κB; IκB-α, inhibitor binding protein κB-α; RAGE, receptor for advanced glycation end-product; TGF, transforming growth factor; HRP, horseradish peroxidase; Ccr, creatinine clearance; AGE, advanced glycation end-product; AU, arbitrary unit; ECM, extracellular matrix.
- Received April 27, 2006.
- Accepted July 7, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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