aplysin and Chemical-and-Drug-Induced-Liver-Injury

We investigated the protective effects and possible mechanisms of Aplysin against alcohol-induced liver injury. Rats were given daily either alcohol only (alcohol model group; 8 to 12 mL/kg body weight), one of three doses of Aplysin (50, 100, or 150 mg/kg Aplysin) plus alcohol, or volume-matched saline. After 6 weeks, the effects of Aplysin were assessed in terms of changes in histology, biochemical indices, and DNA oxidative damage. Potential mechanisms were analyzed through measurements of lipid peroxidation, antioxidant defense systems, expression of cytochrome P450 2E1, and expression of apoptosis-related genes. We found that Aplysin significantly protected the liver against alcohol-induced oxidative injury, evidenced by improved hepatic histological structure, inhibited alcohol-induced elevation of serum biochemical indices, attenuated extents of hepatocellular DNA damage. At a mechanistic level, Aplysin alleviated alcohol-induced oxidative stress as illustrated by the revivification of erythrocyte membrane fluidity, the attenuation of glutathione depletion, the restoration of antioxidase activities, and reduced malondialdehyde overproduction. Furthermore, the mRNA levels of Bax, cytochrome c, and cytochrome P450 2E1 were significantly down-regulated, whereas those of Bcl-2 and caspase-9 and caspase-3 were markedly up-regulated. These findings suggest that Aplysin provides significant protection against alcohol-induced liver injury, possibly through alleviating oxidative damage and modulating endogenous apoptosis-related genes expression.. Many natural components derived from alga have been used in the food, cosmetics, and biomedicine industries. Aplysin, a marine bromosesquiterpene, was extracted from the red alga Laurencia tristicha, which could effectively protect against alcohol-induced liver injury, might be a potential natural sources for preventing alcoholic liver damage.

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP2E1; DNA Damage; Erythrocyte Membrane; Ethanol; Gene Expression; Glutathione; Hydrocarbons, Brominated; Laurencia; Lipid Peroxidation; Liver; Male; Malondialdehyde; Oxidative Stress; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Sesquiterpenes

This study investigated the protective effect of aplysin on the liver and its influence on inflammation and the gut microbiota in rats with ethanol-induced liver injury.. Male Sprague-Dawley rats were randomly assigned to an alcohol-containing liquid diet, control liquid diet or treatment with aplysin for 8 weeks. Hepatic and intestinal histopathological analysis was performed, and cytokine levels and the intestinal mucosal barrier were assessed. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) and 16S rDNA high-throughput sequencing were performed to provide an overview of the gut microbiota composition.. Chronic alcohol exposure caused liver damage in rats. Serum aspartate aminotransferase (AST), aminotransferase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) activities in liver tissue were higher than in the control group. Alcohol administration elevated the levels of serum transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) and reduced interleukin-10 (IL-10) levels compared with those of control rats. In addition, the levels of plasma endotoxin, diamine oxidase (DAO), and fatty acid-binding protein 2 (FABP2) in the alcohol group were higher than in the control group. The results of ERIC-PCR indicated that aplysin treatment shifted the overall structure of the ethanol-disrupted gut microbiota toward that of the control group. One hundred twenty to 190 genera of bacteria were detected by high throughput sequencing. Alcohol-induced changes in the gut microbial composition were detected at the genus level. These alcohol-induced effects could be reversed with aplysin treatment.. These results suggest that aplysin exerts a protective effect on ethanol-induced hepatic injury in rats by normalizing fecal microbiota composition and repairing intestinal barrier function.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cytokines; DNA, Bacterial; DNA, Ribosomal; Enterobacteriaceae; Ethanol; Gastrointestinal Microbiome; Hydrocarbons, Brominated; Liver; Male; Rats; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Sesquiterpenes