ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Cigarette Smoke Toxins-Induced Mitochondrial Dysfunction and Pancreatitis Involves Aryl Hydrocarbon Receptor Mediated Cyp1 Gene Expression: Protective Effects of Resveratrol.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- A prognostic model based on metabolic indicators for recurrent acute pancreatitis in hypertriglyceridemia patients: a retrospective cohort study.Annals of medicine · 2026Article
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- [Machine Learning-Assisted Efficacy Evaluation of Resveratrol Therapy in a Mouse Model of Acute Pancreatitis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Resveratrol improved mitochondrial biogenesis by activating SIRT1/PGC-1α signal pathway in SAP.Scientific reports · 2024Article
- Molecular mechanism and potential role of mitophagy in acute pancreatitis.Molecular medicine (Cambridge, Mass.) · 2024Review
- A tryptophan-derived uremic metabolite/Ahr/Pdk4 axis governs skeletal muscle mitochondrial energetics in chronic kidney disease.JCI insight · 2024Article
- The Role of Endocrine Disruption Chemical-Regulated Aryl Hydrocarbon Receptor Activity in the Pathogenesis of Pancreatic Diseases and Cancer.International journal of molecular sciences · 2024Review
- Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease.Circulation research · 2023Article
- Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Benzo(a)pyrene and cardiovascular diseases: An overview of pre-clinical studies focused on the underlying molecular mechanism.Frontiers in nutrition · 2022Review
- Diabetes and SARS-CoV-2-Is There a Mutual Connection?Frontiers in cell and developmental biology · 2022Review
- Review
- Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells.Molecular biology reports · 2021Article
- Resveratrol attenuates angiotensin II-induced cellular hypertrophy through the inhibition of CYP1B1 and the cardiotoxic mid-chain HETE metabolites.Molecular and cellular biochemistry · 2020Article
- Mitochondrially targeted cytochrome P450 2D6 is involved in monomethylamine-induced neuronal damage in mouse models.The Journal of biological chemistry · 2019Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
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Abstract
We previously reported that mitochondrial CYP1 enzymes participate in the metabolism of polycyclic aromatic hydrocarbons and other carcinogens leading to mitochondrial dysfunction. In this study, using Cyp1b1-/-, Cyp1a1/1a2-/-, and Cyp1a1/1a2/1b1-/- mice, we observed that cigarette and environmental toxins, namely benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induce pancreatic mitochondrial respiratory dysfunction and pancreatitis. Our results suggest that aryl hydrocarbon receptor (AhR) activation and resultant mitochondrial dysfunction are associated with pancreatic pathology. BaP treatment markedly inhibits pancreatic mitochondrial oxygen consumption rate (OCR), ADP-dependent OCR, and also maximal respiration, in wild-type mice but not in Cyp1a1/1a2-/- and Cyp1a1/1a2/1b1-/- mice. In addition, both BaP and TCDD treatment markedly affected mitochondrial complex IV activity, in addition to causing marked reduction in mitochondrial DNA content. Interestingly, the AhR antagonist resveratrol, attenuated BaP-induced mitochondrial respiratory defects in the pancreas, and reversed pancreatitis, both histologically and biochemically in wild-type mice. These results reveal a novel role for AhR- and AhR-regulated CYP1 enzymes in eliciting mitochondrial dysfunction and cigarette toxin-mediated pancreatic pathology. We propose that increased mitochondrial respiratory dysfunction and oxidative stress are involved in polycyclic aromatic hydrocarbon associated pancreatitis. Resveratrol, a chemo preventive agent and AhR antagonist, and CH-223191, a potent and specific AhR inhibitor, confer protection against BaP-induced mitochondrial dysfunction and pancreatic pathology.
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Registered trials
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