Antioxidant, antiapoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice.

L-carnitine (LC) and selenium (Se) have significant protective and antioxidant effects on several tissues. Cadmium (Cd), widely used in some industries and emitted from fossil fuels, is a heavy metal having a number of side effects, including hepatotoxicity. This study aims to assess the ameliorative function of both LC and SeCl4 on cadmium chloride (CdCl2)-induced liver toxicity. In total, 70 male mice included in this study were allocated to seven groups: control, CdCl2, LC, SeCl4, CdCl2 plus SeCl4, CdCl2 plus LC, CdCl2 plus SeCl4 and LC groups. Hepatic aminotransferase (aspartate aminotransferase [AST] and alanine transaminase [ALT]) activity and tumor necrosis factor-alpha [TNF-α] levels, as well as the antioxidant biomarkers (superoxide dismutase [SOD], glutathione reductase [GRx], glutathione-S-transferase [GST] and catalase [CAT], were examined. Histological and transmission electron microscopic [TEM] variations in the liver were used as indicators of liver damage after the administration of CdCl2-alone or CdCl2 with LC, SeCl4, or both. Genotoxic effects of CdCl2 were also evaluated and the possible roles of SeCl4 and/or LC on the expression of the antioxidant enzymes were studied. Results showed that administration of LC and SeCl4 decreased CdCl2-induced increase in ALT and AST levels and reduced oxidative stress to normal levels. In addition, LC combined with SeCl4 had a highly synergistic effect and elevated significantly the enzymatic antioxidants and decreased lipid peroxidation levels compared with those in the CdCl2-treated group. It is clear from the data that both LC and SeCl4 inhibit liver injury and improve the redox state in mice.

Ameliorative effect of bone marrow-derived stem cells on injured liver of mice infected with Schistosoma mansoni.

The technique of stem cells or hepatocytes transplantation has recently improved in order to bridge the time before whole-organ liver transplantation. In the present study, unfractionated bone marrow stem cells (BMSCs) were harvested from the tibial and femoral marrow compartments of male mice, which were cultured in Dulbecco's modified Eagle's medium (DMEM) with and without hepatocyte growth factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice on their 8th week post-infection. Mice were sacrificed monthly until the third month of bone marrow transplantation, serum was collected, and albumin concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed. On the other hand, immunohistopathological and immunohistochemical changes of granuloma size and number, collagen content, and cells expressing OV-6 were detected for identification of liver fibrosis. BMSCs were shown to differentiate into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the group of mice treated with BMSCs than in the untreated control group. Also, granuloma showed a marked decrease in size and number as compared to the BMSCs untreated group. Collagen content showed marked decrease after the third month of treatment with BMSCs. On the other hand, the expression of OV-6 increased detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs with or without HGF infusion significantly enhanced hepatic regeneration in S. mansoni-induced fibrotic liver model and have pathologic and immunohistopathologic therapeutic effects. Also, this new therapeutic trend could generate new hepatocytes to improve the overall liver functions.