Potential impact of mesenchymal stem cells on nephrotoxicity induced by gamma irradiation and antiepileptic drugs cotherapy in rats

Abstract

AbstractThe goal of this study was to assess the influence of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) on the nephrotoxicity induced by fractionated doses of gamma irradiation (Rad) and the cotherapy of levetiracetam and oxcarbazepine in male rats. Adult rats were randomly divided into four groups. Group I: Control, Group II: antiepileptic drugs (AEDs), Group III: AEDs +Rad and Group IV: AEDs + Rad + MSCs. Rats treated with AEDs and exposed to fractionated doses of γ‐irradiation displayed a discernible increase in serum urea, creatinine, kidney injury marker, kidney malondialdehyde, transforming growth factor beta (TGF‐β) and the relative expression of Smad3 along with a decrease in the relative expression of Smad7 and glutathione level. Alternatively, groups treated with BM‐MSCs with AEDs and Rad showed a substantial modification in the majority of the evaluated parameters and looked to be successful in reducing the hazards of the combination therapy of AEDs and radiation. The reno‐histopathological study supports the biochemical analysis. In conclusion, BM‐MSCs exhibited therapeutic potential against nephrotoxicity induced by fractionated doses of γ‐irradiation and AEDs. The outcome was brought about by the downregulation of the TGF‐β/Smad pathway. BM‐MSCs might be suggested as a valuable therapeutic strategy to overcome kidney injury induced by gamma irradiation during AEDs cotherapy.