Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats

摘要

Background: Endothelin-1 (ET-1) is a vasoconstrictor peptide that mediates cell proliferation, fibrosis, and inflammation. ET-1 has 2 receptors A and B. Objectives: The present study investigated whether administration of ET-1 receptor type A antagonist leads to protect cisplatin (CP) induced nephrotoxicity in ovariectomized-estradiol (Es) treated rats. Materials and Methods: Thirty-six ovariectomized Wistar rats were divided into 6 groups. Group 1 received CP (2.5 mg/kg/day) for one week. Groups 2 and 3 received 2 different doses of Es (0.25 and 0.5 mg/kg/week) for 3 weeks, but CP was started in the third week. Group 4 was treated as group 1, but bosentan (BOS, 30 mg/kg/day) was also added. Groups 5 and 6 treated similar to groups 2 and 3 but CP and BOS were added in the third week. At the end of the experiment, blood samples were obtained, and the animals were sacrificed for histopathological investigation of kidney tissue. Results: The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) increased by CP; however, BOS significantly elevated the BUN and Cr levels that were increased by CP administration (P Conclusions: According to our findings, BOS could not protect renal functions against CP-induced nephrotoxicity. In contrast, Es alone or accompanied with BOS could protect the kidney against CP-induced nephrotoxicity via reduction of BUN, Cr, and KTDS.