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5‐ALA/SFC Attenuated Binge Alcohol–Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats
Author(s) -
Liu Chi,
Zhu Ping,
Fujino Masayuki,
Zhu Shuoji,
Ito Hidenori,
Takahashi Kiwamu,
Nakajima Motowo,
Tanaka Tohru,
Zhuang Jian,
Li XiaoKang
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14117
Subject(s) - liver injury , alcoholic liver disease , endocrinology , medicine , liver disease , chemokine , alcohol , inflammation , binge drinking , chemistry , ethanol , genetically modified mouse , transgene , immunology , biochemistry , cirrhosis , gene , alcohol consumption
Background This study aimed to investigate the protective effect of 5‐aminolevulinic acid (5‐ALA) and sodium ferrous citrate (SFC) against binge alcohol–induced gut leakiness and inflammatory liver disease in HIV transgenic (TG) rats. Methods TG rats were treated with 3 consecutive doses of binge ethanol (EtOH) with or without 5‐ALA/SFC. Blood and liver tissue samples were collected at 6 hours following the last dose of EtOH. Results Compared with the wild‐type (WT) rats, the TG rats showed increased sensitivity to alcohol‐mediated inflammation, as evidenced by the significantly elevated levels of serum endotoxin, AST, ALT, ED1, and ED2 staining in liver. In contrast, 5‐ALA/SFC improved the above biochemical and histochemical profiles. 5‐ALA/SFC also attenuated the up‐regulated mRNA expression of leptin and CCL2. Furthermore, down‐regulated intestinal ZO‐1 protein expression was also inhibited by 5‐ALA/SFC. Moreover, the expressions of HO‐1, HO‐2, Sirt1, and related signal transduction molecules in liver were increased by 5‐ALA/SFC. These results demonstrated that 5‐ALA/SFC treatment ameliorated binge alcohol exposure liver injury in a rat model of HIV‐infected patients by reducing macrophage activation and expression of inflammatory cytokines/chemokines, and by inducing HO‐1, HO‐2, and Sirt1 expression. Conclusions Taken together, these findings suggested that treatment with 5‐ALA/SFC has a potential therapeutic effect for binge alcohol exposure liver injury in HIV‐infected patients.