RESUMO
OBJECTIVE: To study the effect of selenium-enriched Bifidobacterium longum on alcoholic liver damage and its mechanism. METHODS: Alcoholic liver damage of female C57/BL6 mice were induced with 20% alcohol for 42 d, at the same time 50 or 100 mg•kg-1 selenium-enriched Bifidobacterium longum were administrated respectively. Mice livers were collected for calculating liver index, HE staining and measuring liver tissue malondialdehyde (MDA) and superoxide dismutase (SOD) level. Serum were collected for measurement of alanine transarninase (ALT), aspartate aminotransferase (AST),γ-glutamyltransferase (GGT) and tumor necrosis factor α (TNF-α) levels. The mRNA levels of liver SREBP-1c, AMPK and PPAR-α were measured with Real-time PCR. RESULTS: Selenium-enriched Bifidobacterium longum inhibited the increase in liver index and inflammation index induced with alcohol. Selenium-enriched Bifidobacterium longum also inhibited alcohol induced ALT, AST, GGT and TNF-α levels increase; decreased liver MDA levels and increased liver SOD levels. Selenium-enriched Bifidobacterium longum down-regulated SREBP-1c mRNA and up-regulated AMPK and PPAR-α mRNA levels of mice liver. CONCLUSION: Selenium-enriched Bifidobacterium longum protects mice from alcohol induced liver damage in a dose dependent manner. Its protective mechanism might be anti-oxidation, inflammation inhibition and improvement of lipid metabolism.
RESUMO
Serum palmitic acid (PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes. Ethanol (EtOH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of EtOH on PA-induced lipotoxicity in the liver. Our results indicated that EtOH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. EtOH intensified PA-caused endoplasmic reticulum (ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. EtOH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP(-/-) mice treated with EtOH and high fat diet (HFD), EtOH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of EtOH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing EtOH and saturated fatty acid-induced metabolic complications.