TAURINE AMELIORATES CHRONIC STREPTOZOCIN-INDUCED DIABETIC NEPHROPATHYIN RATS

We examined the effect of two endogenous antioxidant agents, taurine a nd vitamin E, on renal function in experimental diabetes. Male Sprague -Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment wi th 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival ra te was similar (70-90%) in all groups except vitamin E-treated animals , of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with norma l or insulin-treated diabetic rats. Taurine supplementation reduced to tal proteinuria and albuminuria by nearly 50%. This treatment also pre vented glomerular hypertrophy, preserved immunohistochemical staining for type TV collagen in glomeruli, and diminished glomerulosclerosis a nd tubulointerstitial fibrosis in diabetic animals. The changes in ren al function and structure in taurine-treated diabetic rats were associ ated with normalization of renal cortical malondialdehyde content, low ering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in sk in collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E suppleme ntation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylati on end products (AGEs) in skin collagen. We conclude that administrati on of taurine, but not vitamin E, to rats with STZ-diabetes ameliorate s diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and le ss accumulation of AGEs within the kidney.