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Effect of dietary zinc on ethanol induced autophagy in mice
Author(s) -
Liuzzi Juan P,
Liu Xinyi P,
Doan Huong P,
Nambiar Sruthi P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb367
Subject(s) - autophagy , chemistry , ethanol , chloroquine , toxicity , oil red o , medicine , endocrinology , zinc , pharmacology , saline , lipid droplet , biochemistry , biology , immunology , adipose tissue , apoptosis , organic chemistry , malaria , adipogenesis
Autophagy is a highly conserved catabolic process that involves degradation of damaged or superfluous proteins and organelles. Recent studies have showed that autophagy is a protective mechanism against ethanol toxicity. Alcohol induced liver damage is known to be attenuated by zinc supplementation. However, the role of zinc in autophagy has just begun to be studied. In this study, the effect of zinc deficiency, adequacy and excess on hepatic autophagic flux, lipid accumulation and liver injury was examined in C57BL/6 mice acutely exposed to ethanol. In addition, the effect of ethanol and the autophagy inhibitor, chloroquine, on the expression of methallothionein (MT) was evaluated. Ninety six C57BL/6 male mice were fed diets containing three levels of zinc content: low (1.0mg/kg), adequate (30mg/kg), and supplemented (150mg/kg) for four weeks. Thereafter, mice were injected intraperitoneally with saline or chloroquine (60m/kg bodyweight). Subsequently, mice were administered either water or ethanol (4.5g/kg body weight) by gavage. Mice were sacrificed at 14h and 24h after ethanol treatment. Hepatic autophagic flux was assessed by measuring LC3II/LCI ratio, Beclin1, and p62/SQSTM1 levels in presence and absence of chloroquine. Liver damage was determined by measuring the activity of aspartate amino transferase in serum and by histological analysis. Hepatic lipid accumulation was evaluated by measuring triglyceride content in liver and by oil red staining. MT mRNA levels were measured by RT‐PCR. The dietary treatments did not affect food intake and body weight. Ethanol treatment induced autophagic flux; however, this effect was strongest in mice fed high zinc diet. The stimulatory effect of high zinc intake on autophagic flux was maximum at 24h. Zinc deficiency was associated with increased ethanol induced steatosis and liver injury. Chloroquine treatment exacerbated ethanol induced steatosis and liver damage in mice fed zinc adequate or high zinc diet. Lastly, ethanol treatment significantly increased mRNA levels of MT. However, chloroquine treatment suppressed MT expression in mice exposed to ethanol. The results from this study indicate that ethanol induced autophagy is influenced by zinc status and support the notion that autophagy plays an important role in the protection against ethanol toxicity conferred by zinc. Support or Funding Information NIH1R03AA022451‐01