The Role of Bone Marrow-Derived Mesenchymal Stromal Cells and Hesperidin in Ameliorating Nephrotoxicity Induced by Cisplatin in Male Wistar Rats.

Abstract

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) and antioxidants opened the way for many effective therapeutic experiments against damaged organs like kidneys. Nephrotoxicity is the main complication of chemotherapeutic drugs. Therefore, the present study aimed to investigate the efficacy of BM-MSCs and hesperidin to treat cisplatin-induced nephrotoxicity in rats. Fifty rats were divided into five equal groups of 10 each. Group-I served as a control group, group-II received a single dose of cisplatin (7.5 mg/kg) intraperitoneally to induce nephrotoxicity, group-III received a daily dose of hesperidin (40 mg/kg) orally for four weeks, and on the 5^th day cisplatin was administered an hour before hesperidin administration. Group-IV consisted of cisplatin-treated rats that were intravenously injected with 1х10⁶ BM-MSCs cells/rat once per week. Group V contained cisplatin-treated rats that received a combination of hesperidin and BM-MSCs with the same dosage regimes. After four weeks, serum and kidney samples were collected for biochemical, histological, and immunohistochemical examinations were performed. Cisplatin administered rats showed deteriorated biochemical parameters and severe degenerative changes in renal tissue. Both single and combined hesperidin and BM-MSCs treatments restored the renal biochemical parameters. Histologically, the renal tissues significantly improved in the BM-MSCs treated group in comparison with the hesperidin treated group. Moreover, combined treatment (i.e., group V) showed complete restoration of the normal architecture in the renal tissue. Our data suggest that the combined treatment of BM-MSCs and hesperidin has a potent renoprotective efficacy against cisplatin-induced nephrotoxicity rather than the single treatment.