ArticleRedox biology2019
Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis: Protection by the ALDH2 activator Alda-1.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- α-Amanitin aggravates hepatic injury by activating oxidative stress and mitophagy via peroxiredoxin 6 inhibition.Immunologic research · 2025Article
- Aldehyde Dehydrogenase 2 Lactylation Aggravates Mitochondrial Dysfunction by Disrupting PHB2 Mediated Mitophagy in Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective.Kidney diseases (Basel, Switzerland) · 2024Review
- [Study based on the acetaldehyde dehydrogenase 2 gene polymorphism and acetaminophen-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Association of IL-8 and CXCR2 with AST/ALT Ratio in Liver Abnormalities Screening during Oxidative Stress Injury Caused by VCM.Journal of toxicology · 2024Article
- HBV infection may sensitize patients to alcoholic steatohepatitis and non-alcoholic steatohepatitis.Gastroenterology report · 2024Article
- Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice.Nature communications · 2023Article
- Western diet unmasks transient low-level vinyl chloride-induced tumorigenesis; potential role of the (epi-)transcriptome.Toxicology and applied pharmacology · 2023Article
- Vinyl chloride enhances high-fat diet-induced proteome alterations in the mouse pancreas related to metabolic dysfunction.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification.International journal of molecular sciences · 2023Review
- Aldehyde dehydrogenase 2 alleviates mitochondrial dysfunction by promoting PGC-1α-mediated biogenesis in acute kidney injury.Cell death & disease · 2023Article
- Improvement of obesity-induced fatty liver disease by intermittent hypoxia exposure in a murine model.Frontiers in pharmacology · 2023Article
- Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation.Theranostics · 2023Review
- Effect of vinyl chloride exposure on cardiometabolic toxicity.Environmental toxicology · 2022Article
- Improvements in protective measures in factories with acetylene hydrochlorination and ethylene oxychlorination techniques declined risk assessment levels and affected liver health status.Frontiers in public health · 2022Article
- Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?Acta pharmaceutica Sinica. B · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Vinyl chloride (VC), an abundant environmental contaminant causes steatohepatitis at high levels, but is considered safe at lower (i.e., sub-OSHA) levels. However, we have previously shown that even lower VC levels exacerbate experimental nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD). Mitochondrial oxidative injury and subsequent metabolic dysfunction appeared to play key roles in mediating this interaction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) serves as a key line of defense against endogenous and exogenous reactive aldehydes. The current study therefore tests the hypothesis that allosteric activation of ALDH2 with Alda-1 will protect against VC-enhanced NAFLD. Mice were exposed to low VC concentrations (<1 ppm), or room air for 6 h/day, 5 days/week for 12 weeks, while on HFD or low-fat control diet (LFD). Some mice received Alda-1 (20 mg/kg i.p., 3 × /week) for the last 3 weeks of diet/VC exposure. Indices of liver injury, oxidative stress, metabolic and mitochondrial (dys)function were measured. As observed previously, low-dose VC did not cause liver injury in control mice; while liver injury caused by HFD was enhanced by VC. VC decreased hepatic ALDH2 activity of mice fed HFD. Alda-1 attenuated oxidative stress, liver injury, and dysmetabolism in mice exposed to HFD+VC under these conditions. Importantly, alterations in mitochondrial function caused by VC and HFD were diminished by Alda-1. Previous studies have indicated that liver injury caused by HFD is mediated, at least in part, by enhanced mitochondrial autophagy (mitophagy). Here, Alda-1 suppressed PINK1/PARKIN-mediated mitophagy. Taken together, these results support the hypothesis that ALDH2 is a critical defense against mitochondrial injury caused by VC in experimental NAFLD. The ALDH2 activator Alda-1 conferred protection against liver damage under these conditions, most likely via increasing clearance of aldehydes and preserving mitochondrial respiratory function.
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