Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats.
The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T(1) (AT(1)) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.
Kanter
Mehmet
M
Department of Histology and Embryology, Faculty of Medicine, Trakya University, Edirne 22030, Turkey. mkanter65@yahoo.com
Sen
Saniye
S
Donmez
Salim
S
Aktas
Cevat
C
Ustundag
Sedat
S
Erboga
Mustafa
M
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007124:Immunoenzyme Techniques; D000077405:Irbesartan; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology*; D008063:Thioctic Acid / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis
D001713:Biphenyl Compounds; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D013311:Streptozocin; D008063:Thioctic Acid; D000077405:Irbesartan