title: Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats.
abstract: It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti-inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin-induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor-α were also determined. Streptozotocin-treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor-α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor-α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti-oxidative and anti-inflammatory mechanisms that appear to be independent of the 5-HT3 receptor.
authors: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors: Anita
authors: A
authors: Barzegar-Fallah
authors: Houman
authors: H
authors: Alimoradi
authors: Firouzeh
authors: F
authors: Asadi
authors: Ahmad Reza
authors: AR
authors: Dehpour
authors: Mojgan
authors: M
authors: Asgari
authors: Massoumeh
authors: M
authors: Shafiei
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D017829:Granisetron / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D013997:Time Factors; D000077526:Tropisetron; D014409:Tumor Necrosis Factor-alpha / Q000652:urine
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D017829:Granisetron; D007211:Indoles; D018836:Inflammation Mediators; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077526:Tropisetron; D014409:Tumor Necrosis Factor-alpha
keywords: diabetic nephropathy; oxidative stress; renal function; tropisetron; tumour necrosis factor-α