Acute paraquat exposure determines dose-dependent oxidative injury of multiple organs and metabolic dysfunction in rats: impact on exercise tolerance.

This study investigated the pathological morphofunctional adaptations related to the imbalance of exercise tolerance triggered by paraquat (PQ) exposure in rats. The rats were randomized into four groups with eight animals each: (a) SAL (control): 0.5 ml of 0.9% NaCl solution; (b) PQ10: PQ 10 mg/kg; (c) PQ20: PQ 20 mg/kg; and (d) PQ30: PQ 30 mg/kg. Each group received a single injection of PQ. After 72 hours, the animals were subjected to an incremental aerobic running test until fatigue in order to determine exercise tolerance, blood glucose and lactate levels. After the next 24 h, lung, liver and skeletal muscle were collected for biometric, biochemical and morphological analyses. The animals exposed to PQ exhibited a significant anticipation of anaerobic metabolism during the incremental aerobic running test, a reduction in exercise tolerance and blood glucose levels as well as increased blood lactate levels during exercise compared to control animals. PQ exposure increased serum transaminase levels and reduced the glycogen contents in liver tissue and skeletal muscles. In the lung, the liver and the skeletal muscle, PQ exposure also increased the contents of malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase and catalase, as well as a structural remodelling compared to the control group. All these changes were dose-dependent. Reduced exercise tolerance after PQ exposure was potentially influenced by pathological remodelling of multiple organs, in which glycogen depletion in the liver and skeletal muscle and the imbalance of glucose metabolism coexist with the induction of lipid, protein and DNA oxidation, a destructive process not counteracted by the upregulation of endogenous antioxidant enzymes.

Food-drug interaction: Anabolic steroids aggravate hepatic lipotoxicity and nonalcoholic fatty liver disease induced by trans fatty acids.

Remains unknown if dietary lipids and anabolic steroids (AS) can interact to modify energy metabolism, hepatic structure and function. We investigated the impact of AS on gene expression, lipid profile, redox status and the development of nonalcoholic fatty liver disease (NAFLD) in mice treated with a diet rich in trans fatty acids. Seventy-two C57BL/6 mice were equally randomized into six groups and treated with a standard diet (SD) or high-fat diet (HFD) alone or combined with testosterone cypionate (10 or 20 mg/kg) for 12 weeks. When combined with a HFD, AS reduced plasma HDL cholesterol levels. It also upregulated SREBP-1, PPARα, SCD-1 and ACOX1 gene expression; plasma and hepatic triglyceride levels; oxidative stress; circulating hepatic transaminase levels and NAFLD severity. Our finding indicated that the activity of antioxidant enzymes such as catalase, glutathione-s-transferase and superoxide dismutase was attenuated by HFD, an effect whose implications for AS-induced hepatotoxicity requires further investigation. Increased lipid, protein and DNA oxidative damage as well as worsening NAFLD in response to the interaction of HFD and AS were also potentially associated with the ability of AS to amplify the activation of regulatory lipid metabolism genes that are also involved in the control of cellular redox balance.