The effect of tropisetron on oxidative stress, SIRT1, FOXO3a, and claudin-1 in the renal tissue of STZ-induced diabetic
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ORIGINAL PAPER
The effect of tropisetron on oxidative stress, SIRT1, FOXO3a, and claudin-1 in the renal tissue of STZ-induced diabetic rats Mahrokh Samadi 1,2 & Shiva Gholizadeh-Ghaleh Aziz 3 & Roya Naderi 1,2 Received: 18 May 2020 / Revised: 29 September 2020 / Accepted: 1 October 2020 # Cell Stress Society International 2020
Abstract Tropisetron is a 5-HT3 receptor antagonist that exerts protective effect against DN. The aim of this study was to investigate the possible molecular mechanisms associated with the renoprotective effects of tropisetron in STZ-induced diabetic rats. Animals were subdivided into 5 equal groups; control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). For induction of type 1 diabetes, a single injection of STZ (55 mg/kg, i.p.) was administered to the animals. Diabetic rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) for 2 weeks. According to the conducted analysis, diabetes led to renal dysfunction (reduction in glomerular filtration rate and urine urea and creatinine as well as elevation in plasma urea and creatinine) and abnormalities in antioxidant defense system (reduction in TAC and elevation in MDA), compared with the control group, which was prevented by tropisetron treatment. Reverse transcription–quantitative polymerase chain reaction and western blotting analysis demonstrated that SIRT1 gene expression decreased while FOXO3a and NF-κB gene expression as well as phosphorylated FOXO3a/total FOXO3a protein ratios and claudin-1 protein level increased in the kidney of diabetic rats compared with the control group. Herein, the results of this research showed that tropisetron treatment reversed these changes. Besides, all these changes were comparable with those produced by glibenclamide as a positive control. Hence, tropisetron ameliorated renal damage due to diabetic nephropathy possibly by suppressing oxidative stress and alteration of SIRT1, FOXO3a, and claudin-1 levels. Keywords Diabetes . Nephropathy . Tropisetron . SIRT1 . FOXO3a . Claudin-1
Introduction Diabetic nephropathy (DN) is a micro-vascular disease which is characterized by excessive proteinuria with the morbidity of 25– 40% (Chen et al. 2011; Ritz et al. 2010). Morphological and functional alterations including glomerular hypertrophy, excessive accumulation of extracellular matrix and glomerulosclerosis, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12192-020-01170-5) contains supplementary material, which is available to authorized users. * Roya Naderi [email protected] 1
Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran
2
Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
3
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
and, ultimately, loss of renal function in the kidney are associated with hyperglycemia and, subsequently, glucose metabolism disord
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