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10.1016/j.pharmthera.2022.108165 [DOI] [PubMed] [Google Scholar] 101.Drost EM, Skwarski KM, Sauleda J, Soler N, Roca J, Agusti A, et al

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Figure 1 Paracetamol for the Early Management of COVID-19: A Critical Viewpoint As discussed above, a precautionary principle regarding the risk of bacterial superinfections and of ACE2 overexpression was the main reason for the decision to discourage the use of NSAIDs ( However, contrary to this opinion, we believe that in the specific case of COVID-19 it is of paramount importance taking due account of the fact that PAC and its metabolites decrease GSH levels, also when given at relatively low doses in healthy volunteers ( Although the drop in hepatic or renal GSH is the most toxicologically relevant interaction (see also below), plasma GSH, free cysteine ( in vitro intracellular GSH in human pulmonary macrophages, type II pneumocytes, and lymphocytes ( Oxidized PAC-quinone imine metabolites have also been shown to form GSH-conjugates which inhibit glutathione reductase (GR): the decreased activity of GR hampers the detoxification and antioxidant capacity of the GSH-GSSG cycle, further aggravating the pro-oxidative status in the cell ( From a different toxicological perspective, a study by Klopi et al

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Our data suggest that a moderate dose of ibuprofen treatment for 7 days significantly altered oxylipins related to different metabolic pathways and revealed significant sex specific differences in livers from ibuprofen treated males and females relative to their vehicle controls