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Inflammation and an increase in antioxidant responses mediated by oxidative stress play an important role in the pathogenesis of acute liver injury (ALI). We utilized in silico prediction of biological activity spectra for substances (PASS) analysis to estimate the potential biological activity profile of deethylated ethoxyquin (DEQ) and hypothesized that DEQ exhibits antioxidant and anti-inflammatory effects in a rat model of carbon tetrachloride (CCl4)-induced ALI. Our results demonstrate that DEQ improved liver function which was indicated by the reduction of histopathological liver changes. Treatment with DEQ reduced CCl4-induced elevation of gene expression, and the activity of antioxidant enzymes (AEs), as well as the expression of transcription factors Nfe2l2 and Nfkb2. Furthermore, DEQ treatment inhibited apoptosis, downregulated gene expression of pro-inflammatory cytokines (Tnf and Il6), cyclooxygenase 2 (Ptgs2), decreased glutathione (GSH) level and myeloperoxidase (MPO) activity in rats with ALI. Notably, DEQ treatment led to an inhibition of CCl4-induced NLRP3-inflammasome activation which was indicated by the reduced protein expression of IL-1β, caspase-1, and NLRP3 in the liver. Our data suggest that DEQ has a hepatoprotective effect mediated by redox-homeostasis regulation, NLRP3 inflammasome, and apoptosis inhibition, which makes that compound a promising candidate for future clinical studies.

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Induction of rheumatoid arthritis in rats was accompanied by an increase in diene conjugate content and glutathione reductase and glutathione peroxidase activities in muscles and blood serum. These changes can be related to mobilization of the glutathione reductase/glutathione peroxidase system coupled with intensification of free radical oxidation. In addition, activity of glucose-6-phosphodehydrogenase and NADP-dependent isocitrate dehydrogenase increased, which can be related to increased demand of NADPH for the glutathione reductase/glutathione peroxidase system. The content of reduced glutathione in muscles and blood serum decreased, probably, due to its utilization for ROS neutralization. Glutathione transferase activity decreased in rheumatoid arthritis, which can be related to shortness of reduced glutathione developing during oxidative stress. The observed shifts in parameters of free radical homeostasis in rheumatoid arthritis are probably associated with intensification of free radical oxidation.

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