The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches
Abstract
An overview is presented on the molecular aspects of toxicity due to paracetamol (acetaminophen) and structural analogues. The emphasis is on four main topics, that is, bioactivation, detoxication, chemoprevention, and chemoprotection. In addition, some pharmacological and clinical aspects are discussed briefly. A general introduction is presented on the biokinetics, biotransformation, and structural modification of paracetamol. Phase II biotransformation in relation to marked species differences and interorgan transport of metabolites are described in detail, as are bioactivation by cytochrome P450 and peroxidases, two important phase I enzyme families. Hepatotoxicity is described in depth, as it is the most frequent clinical observation after paracetamol-intoxication. In this context, covalent protein binding and oxidative stress are two important initial (Stage I) events highlighted. In addition, the more recently reported nuclear effects are discussed as well as secondary events (Stage II) that spread over the whole liver and may be relevant targets for clinical treatment. The second most frequent clinical observation, renal toxicity, is described with respect to the involvement of prostaglandin synthase, N-deacetylase, cytochrome P450 and glutathione S-transferase. Lastly, mechanism-based developments of chemoprotective agents and progress in the development of structural analogues with an improved therapeutic index are outlined.
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BackgroundACETAMINOPHEN-INDUCED HEPATIC NECROSIS. IV. PROTECTIVE ROLE OF GLUTATHIONE
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Ca 2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen 1
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Acetaminophen‐Related Acute Renal Failure without Fulminant Liver Failure
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Cited by
Mechanisms of Acetaminophen-Induced Liver Necrosis
Hinson, J. A., Roberts, D. W., & James, L. P. (2010) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-00663-0_12 · Cited by 1,006
Mammalian Heme Peroxidases: From Molecular Mechanisms to Health Implications
Davies, M. J., Hawkins, C. L., Pattison, D. I., & Rees, M. D. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1927 · Cited by 560
Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs
Oleaga, C., Bernabini, C., Smith, A. S. T., Srinivasan, B., Jackson, M., McLamb, W., Platt, V., Bridges, R., Cai, Y., Santhanam, N., et al. (2016) · Scientific Reports · doi:10.1038/srep20030 · Cited by 442
Myeloperoxidase-derived oxidation: Mechanisms of biological damage and its prevention
Davies, M. J. (2010) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.11-006fr · Cited by 412
Long‐term adverse effects of paracetamol – a review
McCrae, J. C., Morrison, E. E., MacIntyre, I. M., Dear, J. W., & Webb, D. J. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13656 · Cited by 308
Metadata
- Authors
- Bessems, J. G. M., & Vermeulen, N. P. E.
- Venue
- Critical Reviews in Toxicology
- Publisher
- Informa UK Limited
- Published
- 2001-01
- Volume
- 31
- Issue
- 1
- Pages
- 55-138
- ISSN
- 0045-6446 (ISSN-L)
- 1040-8444
- 1547-6898
- OpenAlex
- W2042725396
- Cited by
- 715
- References
- 8
- FWCI
- 13.33
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches. https://app.cochat.ai/papers/10.1080/20014091111677
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- Bessems, J. G. M., & Vermeulen, N. P. E. (2001). Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches. Critical Reviews in Toxicology. https://doi.org/10.1080/20014091111677
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