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Low-grade, transient oxidative signals generated during ozone therapy — including lipid electrophiles such as 4-hydroxynonenal — modify Kelch-like ECH-associated protein 1 (Keap1) and promote nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, which in turn supports the GSH system at four coordinated levels: cystine import via the cystine/glutamate antiporter (xCT), de novo synthesis via glutamate–cysteine ligase, regeneration of reduced glutathione by glutathione reductase, and supply of nicotinamide adenine dinucleotide phosphate (NADPH) from the pentose phosphate pathway
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The results reveal that ibuprofen disturbs not only the COX pathway, but also the CYP450 and lipoxygenase pathways in male mice, suggesting that ibuprofen is likely to generate sex related differences in biologically active oxylipins
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