Melatonin and taurine reduce early glomerulopathy in diabetic rats.
Oxidative stress occurs in diabetic patients and experimental models of diabetes. We examined whether two antioxidants, melatonin and taurine, can ameliorate diabetic nephropathy. Enhanced expression of glomerular TGF-beta1 and fibronectin mRNAs and proteinuria were employed as indices of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50 mg/kg. Two days after streptozotocin, diabetic rats were assigned to one of the following groups: i) untreated; ii) melatonin supplement by 0.02% in drinking water; or iii) taurine supplement by 1% in drinking water. Four weeks after streptozotocin, diabetic rats (n = 6: plasma glucose 516+/-12 mg/dl) exhibited 6.1 fold increase in urinary protein excretion, 1.4 fold increase in glomerular TGF-beta1 mRNA, 1.7 fold increase in glomerular fibronectin mRNA, 2.2 fold increase in plasma lipid peroxides (LPO), and 44 fold increase in urinary LPO excretion above the values in control rats (n = 6: plasma glucose 188+/-14 mg/dl). Chronic administration of melatonin (n = 6) and taurine (n = 6) prevented increases in glomerular TGF-beta1 and fibronectin mRNAs and proteinuria without having effect on blood glucose. Both treatments reduced lipid peroxidation by nearly 50%. The present data demonstrate beneficial effects of melatonin and taurine on early changes in diabetic kidney and suggest that diabetic nephropathy associated with hyperglycemia is largely mediated by oxidative stress.
Ha
H
H
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea. hha4453@yumc.yonsei.ac.kr
Yu
M R
MR
Kim
K H
KH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D004231:Diuresis / Q000187:drug effects; D005353:Fibronectins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress; D011507:Proteinuria; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics
D001786:Blood Glucose; D005353:Fibronectins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013654:Taurine; D008550:Melatonin