5-ALA/SFC Attenuated Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats

Alcohol Clin Exp Res. 2019 Aug;43(8):1651-1661. doi: 10.1111/acer.14117. Epub 2019 Jun 13.

Abstract

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.

Keywords: 5-aminolevulinic acid; Binge Alcohol Exposure Liver Injury; Heme Oxygenase-1; Inflammation; Macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Aminolevulinic Acid / pharmacology*
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Aspartate Aminotransferases / blood
  • Binge Drinking / physiopathology*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Citric Acid
  • Endotoxins / blood
  • Enterobacteriaceae Infections / microbiology
  • Ethanol / adverse effects*
  • Ferrous Compounds
  • HIV Infections / complications
  • HIV-1 / genetics
  • Heme Oxygenase (Decyclizing) / biosynthesis
  • Heme Oxygenase-1 / biosynthesis
  • Hepatitis / blood
  • Hepatitis / complications
  • Hepatitis / prevention & control*
  • Inflammation Mediators / metabolism
  • Intestines / physiopathology*
  • Lipopolysaccharides / blood
  • Liver / metabolism
  • Permeability / drug effects*
  • Rats
  • Rats, Transgenic
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / immunology
  • Sirtuin 1 / biosynthesis
  • Stem Cells
  • Triglycerides / metabolism
  • Zonula Occludens-1 Protein / biosynthesis
  • gag Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CD68 protein, rat
  • Cell Adhesion Molecules, Neuronal
  • Endotoxins
  • Ferrous Compounds
  • Inflammation Mediators
  • Lipopolysaccharides
  • NLGN4X protein, human
  • Receptors, Cell Surface
  • Tjp1 protein, rat
  • Triglycerides
  • Zonula Occludens-1 Protein
  • gag Gene Products, Human Immunodeficiency Virus
  • Citric Acid
  • ferrous citrate
  • Ethanol
  • Aminolevulinic Acid
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • heme oxygenase-2
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Sirt1 protein, rat
  • Sirtuin 1