ArticleMedical principles and practice : international journal of the Kuwait University, Health Science Centre2022
Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could Be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity.
Article in Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed, 7 citations in OpenAlex.
- Membrane-Targeted Consequences of Acetaminophen Toxicity and Off-Target Effects of Antimicrobial Peptides on Host Cell Membranes.International journal of molecular sciences · 2026Review
- Identification of four mechanisms of toxicity for per- and polyfluoroalkyl substances through transcriptomic profiling in human liver spheroids exposed to 24 PFAS.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
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Authors and funding
2 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
objectiveAlthough acetaminophen is one of the most widely used over-the-counter drugs, the mechanisms by which this classical drug exerts analgesic, hepatotoxic, and nephrotoxic effects remain unclear. We hypothesized that acetaminophen might act on cellular membranes of nerves, liver, and kidneys. In order to verify this hypothesis, we studied the interactivity of acetaminophen with biomimetic lipid bilayer membranes by comparing with structurally related phenacetin.
methodsLiposomal membranes (unilamellar vesicles suspended in the buffer of pH 7.4) were prepared with phospholipids and cholesterol to mimic the membrane lipid composition of neuronal cells, hepatocytes, and nephrocytes. They were subjected to reactions with acetaminophen and phenacetin at clinically relevant concentrations, followed by measuring fluorescence polarization to determine their membrane interactivity to modify membrane fluidity.
resultsAcetaminophen and phenacetin interacted with neuro-mimetic and hepato-mimetic membranes to increase membrane fluidity at 10-100 μM. Both drugs were more effective in fluidizing hepato-mimetic membranes than neuro-mimetic membranes. Although the relative membrane-interacting potency was phenacetin >> acetaminophen in neuro-mimetic and hepato-mimetic membranes, such membrane effects conflicted with their relative analgesic and hepatotoxic effects. Acetaminophen and phenacetin strongly interacted with nephro-mimetic membranes to increase membrane fluidity at 2-100 μM and 0.1-100 μM, respectively. Phenacetin interacted significantly with nephro-mimetic membranes at lower concentrations (<2 μM) than acetaminophen, which was consistent with their relative nephrotoxic effects.
conclusionIn comparison with phenacetin, lipid composition-dependent membrane interactivity of acetaminophen could be related to nephrotoxicity but not to analgesic activity and hepatotoxicity.
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