Effect of Silymarin and/or Bone Marrow-Derived Mesenchymal Stem Cells on Carbon Tetrachloride-Induced Hepatotoxicity in Rats
Tariq I Almundarij, Abdel Kader A Zaki, Yousef M. Alharbi, Saleh M. Albarrak, Tamim S Alqarawi and Faten A M Abo-Aziza
Hepatic fibrosis has been diagnosed in more than 10% of the world population and is still with limited treatments. This work explored whether silymarin and bone marrow-derived mesenchymal stem cells (BM-MSCs) combination can remodel the hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. Fifty rats were equally distributed into five groups: healthy control, CCl4 hepatotoxicity rat model, CCl4 + silymarin treated, CCl4 + BM-MSCs treated, CCl4 + silymarin + BM-MSCs treated. Serum liver function tests, hepatic tissue oxidative enzymes and cytokines were assessed. Akt and P-Akt proteins expression was estimated by Western blot. Livers were examined histologically using two types of staining. The cultured BMMSCs positively expressed CD73, CD105, and CD29 and negatively expressed CD34 and CD45. The morphology of the BM-MSCs changed from spindle-shaped to oblate-shaped after hepatogenic differentiation. In CCl4 hepatotoxicity rat model, a significant increase in transaminases (P<0.01), bilirubin (P<0.05), malondialdehyde, and TNF-α (P<0.01) was observed. There was a noticeable drop in the catalase (P<0.01), superoxide dismutase, glutathione peroxidase, interleukins (IL) -4, -10, and -17 (P<0.05). A marked elevated IL-17 and reduced TNF-α levels were noticed in the rats treated with silymarin (P <0.05). Treatment with BM-MSCs or the combination of silymarin and BM-MSCs restored the cytokine levels and ameliorated all the hepatic bio indices to normal levels. According to the obtained results, a combination of BM-MSCs and silymarin could alleviate liver hepatotoxicity. Furthermore, the results were supported by the Akt/p-Akt signaling cascade via down-regulation of Akt phosphorylation.