Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 335, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2020.109332
Keywords
Diabetes; Nephropathy; Tropisetron; Matrix metalloproteinases; TGF-beta 1; P53
Funding
- Nephrology and Kidney Transplant Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
Ask authors/readers for more resources
Treatment with tropisetron in diabetic rats led to significant improvements in blood glucose, serum cystatin C, and urinary total protein levels, indicating enhanced kidney function and reduced renal fibrosis. The expression of TGF-beta 1, p53, MMP-9, and MMP-2 in the kidneys of diabetic rats was regulated by tropisetron, suggesting its potential as a therapeutic agent for diabetic nephropathy.
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 Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-beta 1, 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-beta 1, p53, and expression of extracellular matrix metalloproteinases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available