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Significant curative functions of the mesenchymal stem cells on methotrexate‐induced kidney and liver injuries in rats
Authors:Amany M Gad  Wedad A Hassan  Ebtehal Mohammad Fikry
Institution:Department of Pharmacology, National Organization for Drug Control and Research, Giza, Egypt
Abstract:Mesenchymal stem cells (MSCs) curative effects on methotrexate (MTX)‐induced kidney and liver injuries remain elusive. Therefore, rats were divided into five groups, rats received MTX orally (14 mg/kg) as a single dose/week for 2 weeks, groups 3 and 4 were injected once with 2 × 106 cells bone marrow MSCs and adipose‐derived MSCs, respectively. The last group administered dexamethasone (DEX) (0.5 mg/kg, p.o) for 7 days. MTX caused marked increase in malondialdehyde and nitrite/nitrate concentrations. However, MTX administration decreased reduced glutathione content plus catalase activity. In addition, MTX caused a significant increment in kidney and liver biomarkers levels. Moreover, MTX showed renal tubules vacuolation and necrosis of hepatocytes, as well expression of caspase‐3 and nuclear factor kappa beta in kidney and liver tissues were observed. MSCs treatment alleviated previous side effects induced by MTX. MSCs improved nephrotoxicity and hepatotoxicity induced by MTX to a better extent as compared with DEX.
Keywords:adipose‐derived mesenchymal stem cells  bone marrow mesenchymal stem cells  hepatotoxicity  methotrexate  nephrotoxicity
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