The pyridoindole antioxidant stobadine attenuates albuminuria, enzymuria, kidney lipid peroxidation and matrix collagen cross-linking in streptozotocin-induced diabetic rats.
The aim of the present study was to investigate the effect of dietary supplementation with the pyridoindole antioxidant stobadine on kidney status and function in streptozotocin-induced diabetic rats. Diabetic male Wistar rats were fed a standard diet for 32 weeks or a diet supplemented with stobadine (0.05% w/w). The diabetic state was characterized by significantly elevated plasma levels of glucose, HbA1c and urea, severe reduction of total body weight and relatively enlarged kidneys. Elevated levels of conjugated dienes were recorded in the diabetic kidney confirming the presence of oxidative stress in diabetic animals. All diabetic rats showed marked proteinuria and albuminuria along with elevated excretion of the enzyme N-acetyl-beta-D-glucosaminidase. Long-term treatment of diabetic animals with stobadine significantly reduced total proteinuria, albuminuria and enzymuria, yet left the overall physical and glycemic status unaffected. It reduced oxidative damage of kidney tissue as shown by decreased conjugated diene level, and decreased matrix collagen cross-linking, as indicated by decreased breaking time values of rat tail tendons. These beneficial effects of stobadine, supported also by histological findings, may be brought about by virtue of the combination of its antioxidant potential with other effects, e.g., the postulated cholesterol-lowering ability or its ability to alter vascular reactivity and reduce the vascular tone.
Stefek
M
M
Institute of Experimental Pharmacology, Comenius University, Bratislava, Slovakia. exfastfk@savba.sk
Gajdosik
A
A
Tribulova
N
N
Navarova
J
J
Volkovova
K
K
Weismann
P
P
Gajdosikova
A
A
Drimal
J
J
Mihalova
D
D
D000118:Acetylglucosaminidase / Q000652:urine; D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D000975:Antioxidants; D001786:Blood Glucose; D002243:Carbolines; D013311:Streptozocin; D003094:Collagen; D000118:Acetylglucosaminidase; C100106:dicarbine