Effect of antioxidants and mesenchymal stem cells on cisplatin induced renal fibrosis in rats

Abstract

1.1.Background:Mesenchymal stem cells (MSCs) have generated a great deal of excitement and promise as a potential source of all types of cells for cell-based therapeutic strategies. The reparative role of MSCs may be multifunctional and include the secretion of anti-inflammatory cytokines like TGFβ1 to limit apoptosis and dampen the inflammatory response. There are reports suggesting that antioxidants such as N N'-diphenyl-1, 4-phenylenediamine (DPPD) inhibit interstitial fibrosis induced by cisplatin. It inhibits lipid peroxidation and nephrotoxicity induced by cisplatin, where antioxidants make trapping for free radicals. 1.2.Aim:We aimed to investigate the inhibitory potential of either stem cells or DPPD on renal fibrosis in cisplatin induced tubulointerstitial fibrosis rat model. 1.3.Materials and methods:This study was carried on 40 male Sprague-Dawley rats (body weight 170 - 220 g). Rats were divided into 4 groups as follow: Control group, received intravenous saline. Cisplatin group, received cisplatin (6 mg/kg, i.p). DPPD group, received cisplatin (6 mg/kg, i.p) at the start of experiments and three days after cisplatin administration, rats were given DPPD (0.5 g/kg, i.p) every two days. MSCs group, received cisplatin (6 mg/kg, i.p) at the start of experiments and three days after cisplatin administration, rats were given MSCs (1 ×106, i.v) single dose. 14 days after cisplatin (or saline) administration, blood samples were obtained and kidneys were removed for biochemical, histopathology and immunohistochemical markers investigations. 1.4.Results:In addition to the significant rise in urea and creatinine, cisplatin group showed atrophied glomeruli with tubular cells vacuolization and increased collagen deposition. Alpha smooth muscle actin (α-SMA) and fibroblast proliferation marker Ki-67 were found to be increased in renal tissue. Lipid peroxidation and collagen formation markers showed significant elevation. Both MSCs and antioxidant ameliorated cisplatin-induced nephrotoxicity to a great extent and showed marvelous anti-fibrotic effect as evidenced by histopathological, immunohistochemical and biochemical assessments. 1.5.Conclusion:Both MSCs and antioxidant (DPPD) were found to have potent potentials to inhibit tubulointerstitial fibrosis in cisplatin induced nephrotoxicity rat model.