Tetrachloride-induced Acute Liver Injury Research Articles

Effect of Exosomes Derived from Mesenchymal Stem Cell on Hepatic Regeneration in Carbon Tetrachloride Induced Acute Liver Injury in Adult Male Albino Rats. Histological Study

Abstract Background Acute liver failure (ALF) is one of the emergency conditions. Carbon tetrachloride (CCl4) has been widely used to induce experimental hepatic damage. Bone marrow mesenchymal stem cell derived (BM-MSC) exosomes are broadly applied to regenerative approaches for various disorders serving the therapeutic effects of MSCs. Aim of the Work The study analyzed microscopically and biochemically, the regenerative power of the BM-MSC exosomes on the experimentally induced acute hepatic injury. Materials and Methods Fifty-five male adult Wistar albino rats were randomly divided into three groups: Group (I) control group, group II [given a single intraperitoneal injection of carbon tetrachloride (CCl4) (3% vol/vol in olive oil) at 0.05 ml/kg body weight] and group III [given a single tail vein injection of 50 μg of BM-MSC exosomes in 100 μl phosphate buffered saline 24 hours post-CCl4]. The rats were sacrificed after seven days. Biochemical analysis of AST and ALT was performed. Histological examination of liver tissue was performed through light microscopy of hematoxylin and eosin and Masson trichrome stained sections. Transmission electron microscopy (TEM) of liver tissue was carried out. Morphometric and statistical studies were done. Results By light microscopy, H&E-stained sections of Group II (CCl4 treated) revealed altered hepatic architecture with focal cellular infiltration. Congestion and dilatation of portal veins with periportal cellular infiltration were detected. Widening and endothelial discontinuity of the central veins and disorganization and obliteration of some blood sinusoids were demonstrated. Most hepatocytes appeared with darkly acidophilic cytoplasm and condensed nuclei, while others appeared with pyknotic nuclei with vacuolated cytoplasm. In Masson trichrome stained sections, there was a significant increase in the collagen fibers around the central veins and portal triads, and between hepatic cords. TEM examination, hepatocytes displayed irregular heterochromatic nuclei and rarified cytoplasm with plenty of lipid droplets. Hepatic stellate cells were devoid of lipid droplets. The epithelial cell lining the bile ductules had few short microvilli Inflammatory cells were seen near the ductular basal border. Biochemically, there was a significant increase in both ALT & AST levels in group II. The exosomes treated group (III) revealed marked amelioration of the previously mentioned histopathological and biochemical changes compared to the control group. Conclusion The acute CCl4 induced injury was significantly attenuated by BM-MSC exosomes therapy, and is characterized by an increase in hepatocyte proliferation, significant regression of collagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and biochemically.

Characterizations and hepatoprotective effect of polysaccharides from Mesona blumes against tetrachloride-induced acute liver injury in mice

Mesona blumes polysaccharide (MBP), a primary active component extracted from Mesona blumes, has a number of bioactivities. Nevertheless, hepatoprotective activity of MBP has been rarely reported. The purpose of this study is to investigate hepatoprotective effects of MBP on acute liver injury in mice. Results indicated that the MBP could remarkably decrease the increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum caused by tetrachloride (CCl4) treatment (P < 0.05). Medium and high dose of MBP treatment (200 mg/kg body weight, 300 mg/kg body weight) not only prominently enhanced the levels of antioxidant enzymes (superoxide dismutase, SOD) and non-enzyme antioxidants (glutathione, GSH) compared with CCl4-induced, but also dramatically decreased lipid peroxidation levels of liver tissues (P < 0.05). In addition, medium and high doses of MBP significantly enhanced the serum levels of IL-1β and TNF-α (P < 0.05). This study showed that MBP had hepatoprotective activity against acute liver injury caused by CCl4.

Protective effect of polysaccharide from Agaricus bisporus in Tibet area of China against tetrachloride-induced acute liver injury in mice

In this study, we systematically investigated the physicochemical properties, hepatoprotective activities and the underlying mechanisms of Agaricus bisporus polysaccharide (FPS). The physicochemical evaluations indicate that FPS is mainly composed of glucose, mannose, galactose, fucose, arabinose and glucuronic acid with the mole percentages of 70.30%, 8.70%, 12.88%, 0.79%, 5.04% and 1.57%, respectively. The results of methylation analysis indicated that FPS mainly included 1-linked-glc, 1,4-linked-glc, 1,6-linked-glc, 1,3-linked-gal and 1,3,6-linked-man glycosidic bonds. The results from hepatoprotective studies showed that FPS significantly decreased the liver index, serum gamma-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) activities and malondialdehyde (MDA) contents in liver tissue, and increased antioxidant capacities of hepatic glutathione (GSH) and superoxide dismutase (SOD). Furthermore, histological examination of liver tissues showed that FPS alleviated CCl4-induced liver injury. Finally, the Western blot results showed that FPS could significantly decrease the expression levels of TGF-β1 and Smad3 in the liver. These results together suggest that FPS possesses hepatoprotective effect against CCl4-induced liver damage, in part through the downregulation of TGF-β1/Smad signaling pathway, therefore FPS could be considered as a hepatoprotective medicine or functional food.

Metabonomic profiling in study hepatoprotective effect of polysaccharides from Flammulina velutipes on carbon tetrachloride-induced acute liver injury rats using GC–MS

This study was performed to evaluate the hepatoprotective effect of FVP on carbon tetrachloride induced acute liver injury rats. Transaminase levels, antioxidant effect and histopathology were used to assess the recovery of FVP treated acute liver injury rats. Metabolomic analysis of liver homogenate based on GC–MS was used to obtain a global understanding of metabolic change between acute liver injury model rats and FVP-treated rats in order to assess the underlying mechanisms. Multivariate statistical approaches such as principal component analysis and orthogonal projection to latent structure square-discriminant analysis revealed distinctions among the normal, liver injury model, and FVP groups. The results demonstrated that FVP had a hepatoprotective effect on acute liver injury by decreasing AST and ALT levels, enhancing antioxidant effect and attenuating pathological injury. Sixteen metabolites were identified as biomarkers. These biomarkers belonged to glyoxylate and dicarboxylate metabolism, galactose metabolism, glycine, serine and threonine metabolism, glycerolipid metabolism, alanine, aspartate and glutamate metabolism, TCA cycle, pyruvate metabolism, arginine and proline metabolism.