Bone Marrow Mesenchymal Stem Cells Alleviate Methotrexate-Induced Renal Toxicity in leukemia Rats

Background:The chemotherapeutic drug methotrexate (MTX) is administered for managing multiple kinds of cancer.Aim: To determine if bone marrow mesenchymal stem cells (BM-MSCs) might protect rats against renal damage brought on by MTX. Materials and Methods:Rats were divided into five groups : (i) Control group received 2.5 ml saline.(ii) group received MTX as a single IP of 20 mg/Kg body weight.(iii) LEUK group: Benzene-induced leukemia group was injected intravenously every 2 days for 3 consecutive weeks by 0.2 ml benzene.(iv) LEUK/MTX group was injected intravenously every 2 days for 3 consecutive weeks by 0.2 ml benzene and treated by intraperitoneal injection of 2.5 mg/kg.bw/weekMTX for 4 consecutive weeks.(v) (LEUK/ MTX/MSCs) group was injected intravenously every 2 days for 3 consecutive weeks by 0.2 ml benzene and treated by intraperitoneal injection of 2.5 mg/kg.bw/weekMTX for 4 consecutive weeks.This group was also left for 8 days for kidney injury induction then injected intravenously with a single dose of 3x10 6 MSCs.After 4 weeks of MSCs transplantation.Kidney histopathology, Catalase and Superoxide dismutase activities as well as Capase-3 expression levels were examined.Results: Methotrexate induced marked pathological lesion which characterized by focal necrosis, cell infiltration and high immuno-expression ofTGF-β1.Besides, treatment with MSCs successfully improved the severe effects of MTX on the kidney and restored histological architecture which confirmed by oxidative enzymes and apoptosis marker detection.Conclusion: MSCs have the capacity to protect against kidney fibrosis and might be employed as adjuvant treatment.