ArticleAlcoholism, clinical and experimental research2015
Effects of combined alcohol and anti-HIV drugs on cellular stress responses in primary hepatocytes and hepatic stellate and kupffer cells.
Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Oxidative Stress in People Living With HIV: Are Diverse Supplement Sources the Solution?Health science reports · 2025Review
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management.Frontiers in pharmacology · 2022Review
- Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor.Frontiers in pharmacology · 2022Article
- Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium.Stem cell research & therapy · 2021Article
- Review
- Review
- Review
- Ethyl Acetate Fraction ofOxidative medicine and cellular longevity · 2018Article
- Disrupted ER-to-Golgi Trafficking Underlies Anti-HIV Drugs and Alcohol-Induced Cellular Stress and Hepatic Injury.Hepatology communications · 2017Article
- Dissecting the Role of Disturbed ER-Golgi Trafficking in Antivirals and Alcohol Abuse-Induced Pathogenesis of Liver Disorders.Journal of drug abuse · 2017Article
- RAW REHMANNIA RADIX POLYSACCHARIDE CAN EFFECTIVELY RELEASE PEROXIDATIVE INJURY INDUCED BY DUCK HEPATITIS A VIRUS.African journal of traditional, complementary, and alternative medicines : AJTCAM · 2017Article
- Alcohol Use and Human Immunodeficiency Virus (HIV) Infection: Current Knowledge, Implications, and Future Directions.Alcoholism, clinical and experimental research · 2016Review
- Role of endoplasmic reticulum stress in drug-induced toxicity.Pharmacology research & perspectives · 2016Review
- Chronic Effects of Ethanol and/or Darunavir/Ritonavir on U937 Monocytic Cells: Regulation of Cytochrome P450 and Antioxidant Enzymes, Oxidative Stress, and Cytotoxicity.Alcoholism, clinical and experimental research · 2016Article
- Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage.Biomolecules · 2015Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCertain anti-HIV drugs alone or in combination are often associated with liver damages, which are frequently worsened by alcohol consumption. We previously found an endoplasmic reticulum (ER) stress mechanism for the drug- and alcohol-induced hepatic injuries in animal models and in vitro hepatocytes. However, it is unknown whether anti-HIV drugs and alcohol induce similar cellular stress responses and injuries in liver nonparenchymal cells.
methodsPrimary mouse hepatocytes (PMH), kupffer cells (KC), and hepatocellular stellate cells (HSC) were freshly isolated from mouse liver and treated with DMSO, stress-inducing pharmaceutical agents, alcohol alone, or in combination with antiviral ritonavir (RIT), lopinavir (LOP), or efavirenz (EFV). Expression of cellular stress markers, protein colocalization, and cell death were analyzed with immunoblotting, immunocytochemistry, and positive double staining with Sytox green and Hoechst blue, respectively.
resultsExpression of the ER stress markers of BiP, CHOP, and SERCA and the autophagy marker LC3 was significantly changed in PMH in response to combined alcohol, RIT, and LOP, which was companied by increased cell death compared with control. In contrast, although pharmaceutical agents induced ER stress and cell death, no significant ER stress or cell death was found in KC treated with alcohol, RIT, LOP, and EFV singly or in combination. In HSC, alcohol, RIT, LOP, or EFV induced BiP, but not CHOP, SERCA, or cell death compared with vehicle control. Further in PMH, RIT and LOP or in combination with alcohol-induced dose-dependent inhibition of β-actin. Inhibition of β-actin by RIT and LOP was companied with an inhibited nuclear expression of the antioxidant response regulator Nrf2 and reduced GST downstream of Nrf2. Ascorbic acid treatment reduced the alcohol-, RIT-, and LOP-induced cell death.
conclusionsThe data suggest for the first time that sensitivities of hepatocytes and nonparenchymal cells to alcohol and anti-HIV drugs in vitro are different in terms of cellular stress response and cell death injury. Oxidative stress mediated by Nrf2 contributes to the alcohol- and drug-induced toxicity in the hepatocytes.
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