ArticleBritish journal of pharmacology2016
Loss of 5-lipoxygenase activity protects mice against paracetamol-induced liver toxicity.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- Toosendanin Induces Hepatotoxicity by Facilitating ALOX5-Mediated Lipid Peroxidation and Sensitizing Cells to Ferroptosis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites.Journal of pharmaceutical analysis · 2023Article
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- The molecular mechanisms of acetaminophen-induced hepatotoxicity and its potential therapeutic targets.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Hepatic ZBTB22-mediated detoxification ameliorates acetaminophen-induced liver injury by inhibiting pregnane X receptor signaling.iScience · 2023Article
- Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development.Frontiers in physiology · 2023Review
- Experimental Models for Studying Structural and Functional State of the Pathological Liver (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Activation of the eIF2α-ATF4 Pathway by Chronic Paracetamol Treatment Is Prevented by Dietary Supplementation with Cysteine.International journal of molecular sciences · 2022Article
- Disruption of peroxisome proliferator-activated receptor α in hepatocytes protects against acetaminophen-induced liver injury by activating the IL-6/STAT3 pathway.International journal of biological sciences · 2022Article
- Hepatoprotective and antioxidant activities ofPharmaceutical biology · 2020Article
- The diabetes medication canagliflozin promotes mitochondrial remodelling of adipocyte via the AMPK-Sirt1-Pgc-1α signalling pathway.Adipocyte · 2020Article
- Hepatoprotective properties of red betel (Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling.Molecular metabolism · 2020Article
- Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury.Stem cell research & therapy · 2020Review
- Aqueous Partition of Methanolic Extract ofNutrients · 2019Article
- The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPAROxidative medicine and cellular longevity · 2019Article
- Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury.Frontiers in pharmacology · 2019Article
- Organic micropollutants paracetamol and ibuprofen-toxicity, biodegradation, and genetic background of their utilization by bacteria.Environmental science and pollution research international · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeParacetamol (acetaminophen) is the most widely used over-the-counter analgesic and overdosing with paracetamol is the leading cause of hospital admission for acute liver failure. 5-Lipoxygenase (5-LO) catalyses arachidonic acid to form LTs, which lead to inflammation and oxidative stress. In this study, we examined whether deletion or pharmacological inhibition of 5-LO could protect mice against paracetamol-induced hepatic toxicity. EXPERIMENTAL APPROACH: Both genetic deletion and pharmacological inhibition of 5-LO in C57BL/6J mice were used to study the role of this enzyme in paracetamol induced liver toxicity. Serum and tissue biochemistry, H&E staining, and real-time PCR were used to assess liver toxicity. KEY
resultsDeletion or pharmacological inhibition of 5-LO in mice markedly ameliorated paracetamol-induced hepatic injury, as shown by decreased serum alanine transaminase and aspartate aminotransferase levels and hepatic centrilobular necrosis. The hepatoprotective effect of 5-LO inhibition was associated with induction of the antitoxic phase II conjugating enzyme, sulfotransferase2a1, suppression of the pro-toxic phase I CYP3A11 and reduction of the hepatic transporter MRP3. In 5-LO(-/-) mice, levels of GSH were increased, and oxidative stress decreased. In addition, PPAR α, a nuclear receptor that confers resistance to paracetamol toxicity, was activated in 5-LO(-/-) mice. CONCLUSIONS AND IMPLICATIONS: The activity of 5-LO may play a critical role in paracetamol-induced hepatic toxicity by regulating paracetamol metabolism and oxidative stress.
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