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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: UNLABELLED. Meshes: Acetaminophen, Animals, Antiviral Agents, Chemical and Drug Induced Liver Injury, Cytochrome P-450 Enzyme System, Drug Synergism, Interferon Type I, Liver, Male, Mice, Poly I-C, Pregnane X Receptor, RNA, Double-Stranded, RNA, Viral, Receptors, Steroid, Retinoid X Receptor alpha, Toll-Like Receptor 3, Xenobiotics.
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Does polyinosinic-polycytidylic acid suppress acetaminophen-induced hepatotoxicity independent of type I interferons and toll-like receptor 3? Context: Viral infections are often linked to altered drug metabolism in patients; however, the underlying molecular mechanisms remain unclear. Here we describe a mechanism by which activation of antiviral responses by the synthetic double-stranded RNA ligand, polyinosinic-polycytidylic acid (polyI:C), leads to decreased acetaminophen (APAP) metabolism and hepatotoxicity. PolyI:C administration down-regulates expression of retinoic X receptor-α (RXRα) as well as its heterodimeric partner pregnane X receptor (PXR) in mice. This down-regulation results in suppression of downstream cytochrome P450 enzymes involved in conversion of APAP to its toxic metabolite. Although the effects of polyI:C on drug metabolism are often attributed to interferon production, we report that polyI:C can decrease APAP metabolism in the absence of the type I interferon receptor. Furthermore, we demonstrate that polyI:C can attenuate APAP metabolism through both its membrane-bound receptor, Toll-like receptor 3 (TLR3), as well as cytoplasmic receptors.
assistant
This is the first study to illustrate that in vivo administration of polyI:C affects drug metabolism independent of type I interferon production or in the absence of TLR3 through crosstalk between nuclear receptors and antiviral responses. Final Decision: yes