Pourheydar, B and Nikibakhsh, A.A and Naderi, R and Habibi, P and Samadi, M (2021) Renoprotective effects of tropisetron through regulation of the TGF-β1, p53 and matrix metalloproteinases in streptozotocin-induced diabetic rats. Chemico-Biological Interactions, 335. pp. 1-7.
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Abstract
Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/ kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Massonʼs trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF- β1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-β1, p53, and expression of extracellular matrix metalloproteinases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Diabetes Nephropathy Tropisetron Matrix metalloproteinases TGF-β1 p53 |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Unnamed user with email gholipour.s@umsu.ac.ir |
| Date Deposited: | 25 Jan 2021 06:23 |
| Last Modified: | 25 Jan 2021 06:23 |
| URI: | http://eprints.umsu.ac.ir/id/eprint/6091 |
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