Chulalongkorn Medical Journal


Background Paracetamol or acetaminophen (N-acetyl-p-aminophenol; APAP)is a widely used as an analgesic and antipyretic drug. This drughas long time been considered as a safe drug, when used inthe therapeutic levels. However, the adverse effects concerninglong-term APAP usage at the non-hepatotoxicity dosage regardingthe human central nervous system, in particular microglia, remainsunclear.Objective To investigate the effect of short-term (6, 12 and 24 hr.) andlong-term APAP treatments (1, 2, 3 and 4 weeks) on the expressionof the pro-inflammatory cytokine IL-1β in human microglia.Design Experimental researchSetting Department of Biochemistry and Department of Pathology Facultyof Medicine, Chulalongkorn UniversityMaterials and Methods Human microglial (CHME-5) cells were cultured in the presenceof APAP at the concentration determined by MTS assay for 6, 12and 24 hr., representing short-term treatment. As for long-termAPAP treatment, the cells were cultured with APAP for 1, 2, 3 and4 weeks. Cell pellets were subsequently collected andthe expression of the IL-1β in human microglia was determined byWestern Blotting.Results The study shows that long-term APAP treatment inducesmorphological changes in CHME-5 cells. An increase in the numberof amoeboid phagocytic cells with shorten processes isdemonstrated in the long-term APAP- treated cells sincethe second week of treatment. Also, the level of IL-1β expressionis up-regulated in a time-dependent manner while the short-termtreatment shows no alteration, compared to that of controlcultured cells.Conclusions The results demonstrated that long-term paracetamol treatmentactivates human microglial cell morphological changes andup-regulates pro-inflammatory cytokine IL-1β expression.


Faculty of Medicine, Chulalongkorn University

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