Ameliorative role of bosentan, an endothelin receptor antagonist, against sodium arsenite-induced renal dysfunction in rats.

Ashwani Kumar Sharma, Japneet Kaur, Tajpreet Kaur, Balbir Singh, Harlokesh Narayan Yadav, Devendra Pathak, Amrit Pal Singh

Environmental science and pollution research international 2021 Feb

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Arsenic exposure is well documented to cause serious health hazards, such as cardiovascular abnormalities, neurotoxicity and nephrotoxicity. In the present study, we intended to explore the role of bosentan, an endothelial receptor antagonist, against sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Sodium arsenite (5 mg/kg, oral) was administered for 4 weeks to induce renal dysfunction in rats. Sodium arsenite intoxicated rats were treated with bosentan (50 and 100 mg/kg, oral) for 4 weeks. Arsenic led renal damage was demonstrated by significant increase in serum creatinine, urea, uric acid, potassium, fractional excretion of sodium, microproteinuria and decreased creatinine clearance in rats. Sodium arsenite resulted in marked oxidative stress in rat kidneys as indicated by profound increase in lipid peroxides, and superoxide anion generation alongwith decrease in reduced glutathione levels. Hydroxyproline assay highlighted arsenic-induced renal fibrosis in rats. Hematoxylin-eosin staining indicated glomerular and tubular changes in rat kidneys. Picrosirius red staining highlighted collagen deposition in renal tissues of arsenic treated rats. Immunohistological results demonstrated the reduction of renal eNOS expression in arsenic treated rats. Notably, treatment with bosentan attenuated arsenic-induced renal damage and resisted arsenic-led reduction in renal eNOS expression. In addition, sodium arsenite-induced alteration in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, bilirubin), oxidative stress and histological changes were abrogated by bosentan treatment in rats. Hence, we conclude that bosentan treatment attenuated sodium arsenite-induced oxidative stress, fibrosis and reduction in renal eNOS expression in rat kidneys. Moreover, bosentan abrogated arsenic led hepatic changes in rats.

Citation

Ashwani Kumar Sharma, Japneet Kaur, Tajpreet Kaur, Balbir Singh, Harlokesh Narayan Yadav, Devendra Pathak, Amrit Pal Singh. Ameliorative role of bosentan, an endothelin receptor antagonist, against sodium arsenite-induced renal dysfunction in rats. Environmental science and pollution research international. 2021 Feb;28(6):7180-7190