Protective Effect of Mesenchymal Stem Cells on Methotrexate-Induced Acute Toxicity on Liver of Adult Albino Rats

Our study aims at studying acute toxic effects of Methotrexate (MTX) on the liver of adult male albino rats and assessing the protective effect of Mesenchymal Stem Cells (MSCs) on the MTX-induced hepatotoxicity. Twenty-four adult male albino rats were divided into four groups, each of six. Rats in group I served as a negative control. Rats in group II received a single intraperitoneal injection of MTX at a dose of 10 mg/kg. Rats in groups III received MSCs therapy at a single intraperitoneal dose of 1x106 cells per rat. Rats in group IV received MSCs therapy at a single intraperitoneal dose of 2x106 cells per rat. Groups III and IV received MTX injection, same dose as group II. All animals were sacrificed on the 10th day. The liver was retained for histopathological and immunohistochemical examination. The sera were used for biochemical analysis. We demonstrated that MTX significantly increased serum concentrations of liver enzymes, reduced the serum antioxidant catalase enzymes levels, significantly increased serum Malondialdehyde (MDA) concentrations. In addition, it increased iNOS expression and caused prominent histological alterations in the liver. On the other hand, treatment MSCs was effective in significantly improving the liver enzymes, ameliorating the elevations of MDA, increasing catalase enzyme levels and decreasing the hepatic nitrosative stress, and ameliorating the pathological hepatic changes induced by MTX. We concluded that MSCs in both doses (one and two million cells/rat) could ameliorate the hepatotoxicity induced by MTX. Applying such conclusion might have a great impact in future clinical practices