Human bone marrow-derived mesenchymal stromal cells in combination with silymarin regulate hepatocyte growth factor expression and genotoxicity in carbon tetrachloride induced hepatotoxicity in Wistar rats.

Abstract

To evaluate the antimutagenic potential of combination treatment of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) and silymarin and its effect on hepatocyte growth factor levels in CCl4 induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced in adult female Wistar rats using carbon tetrachloride (CCl4 ). Thirty-six rats were randomly divided into six groups with six rats in each group: Group 1 (normal control group), Group 2 (received only CCl 4 ), Group 3 (CCl 4 +low dose BM-MSCs), Group 4 (CCl 4 +high dose BM-MSCs), Group 5 (CCl 4 + silymarin), Group 6 (CCl 4 +silymarin+high dose BM-MSCs). Thirty days after the treatment, blood samples were collected for hepatocyte growth factor estimation. The rats were then killed, bone marrow was extracted for chromosomal aberration assay. Liver tissue was processed for evaluating the DNA fragmentation assay, histopathology, and scanning electron microscopy study. Combination treatment of silymarin and high dose BM-MSCs significantly (P < 0.05) restored the plasma hepatocyte growth factor levels which were comparable with normal levels and exhibited significant antimutagenic and antiapoptotic activity by decreasing the frequency of structural chromosomal aberrations and suppressing the DNA fragmentation in liver tissue samples. The combination treatment produced significant hepatoprotective effect which was supported by histopathology and scanning electron microscopy study. Results indicate that the treatment of BM-MSCs in combination with silymarin had a better hepatoprotective and antimutagenic effect and represents a novel strategy for the treatment of hepatotoxicity.