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

The 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-ß) 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-ß/Smad pathway. BM-MSCs might be suggested as a valuable therapeutic strategy to overcome kidney injury induced by gamma irradiation during AEDs cotherapy.

Acetyl-L-carnitine modulates bleomycin-induced oxidative stress and energy depletion in lung tissues.

BACKGROUND AND PURPOSE: The usefulness of Bleomycin (BLM) as an important antineoplastic drug is usually limited to the development of dose and time-dependent interstitial pneumonitis and pulmonary fibrosis. This study has been initiated to investigate the possible protective effects of acetyl-L-carnitine (AC) against BLM-induced lung toxicity at an early stage of its development. MATERIAL AND METHODS: A total of 40 male Sprague-Dawley rats weighing from 200-250 g each, were divided into 4 groups of 10 animals each. The first group received a daily i.p. injection of normal saline (0.5 ml/200 gm body weight) for 5 consecutive days and served as a control. Animals in the second, third and fourth groups were daily injected intraperitoneally (i.p.) with BLM (15 mg/kg body weight), AC (250 mg/kg body weight) and AC (250 mg/kg) 2 hrs before BLM (15 mg/kg) each for 5 consecutive days, respectively. RESULTS: Treatment of rats with BLM (15 mg/kg) resulted in a significant 3.4 and 2.9 folds increase in malondialdehyde (MDA) and nitric oxide (NO) production in lung tissue, respectively and a significant 39%, 35%, 54% and 44% decrease in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and adenosine triphosphate (ATP), respectively as compared to the control group. Treatment of rats with AC did not lead to any significant change in the mentioned biochemical parameters in the lung tissue. Administration of AC two hours before BLM attenuated BLM-induced increase in MDA and NO and the decrease in GSH, SOD, GSHPx and ATP in lung tissue. CONCLUSION: The present data suggests that the protective effect of AC against BLM-induced acute lung injury could be, at least in part, due to its free radical scavenging properties with the consequent improvement in mitochondrial function and ATP production.