The Comparative Effects of Human Mesenchymal Stem Cell and Platelet Extract on CCl4-Induced Liver Toxicity in Rats

Abstract

Background: Liver toxicity is a state of toxic damage to the liver and is induced by carbon tetrachloride (CCl4), which is wildly used in animal models. Objectives: The aim of this study was to compare the therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSC) and platelet extract (PE) in rats with CCl4 induced liver toxicity. Methods: In this experimental study, liver toxicity was induced by CCl4 in Wistar rats, which were divided into five groups; seven rats were placed in each group. Group I received 0.5 mL/kg olive oil intraperitoneally (IP) twice a week for eight weeks; group II received 1 mL/kg CCl4 1:1 in olive oil IP twice a week for eight weeks; group III received 1 × 106 BM-MSC/rat in 1 mL PBS locally after four weeks of CCl4 injection; group IV received 0.5 mL/kg PE 1:1 in PBS subcutaneously (SC) twice a week for three weeks; and group V received 0.5 mL/kg PE 1:1 in PBS SC twice a week for three weeks after five weeks of CCl4 injection. Blood and tissue samples were collected from all the experimental groups after eight weeks. Histological staining and biochemical analysis were also performed to compare the functional and morphological reconstruction of the liver between groups. Results: Administration of CCl4 resulted in marked alternation in serum hepatic enzymes (AST and ALT), and α-smooth muscle actins deposition. The amount of liver enzyme was significantly reduced in groups III and V compared to group III. Lipid peroxidation expressed by malondialdehyde concentration was significantly decreased in groups III and gr V compared to group III (P < 0.01). The reduction of glutathione levels significantly increased in group III compared to group V (P < 0.01). Histological examination revealed that fatty changes and necrosis were significantly decreased in groups III and V. Both BM-MSC and PE treatments showed a decrease in α-SMA deposition in group II. Conclusions: Cell and platelet therapy methods not only have a direct effect on eliminating reactive oxygen species, they may also affect endogenous antioxidants such as GSH. These methods may be a therapeutic approach for liver damage, particularly for the damages associated with oxidative stress.