Paracetamol-induced metabolic and cardiovascular changes are prevented by exercise training

Paracetamol (PAR) is the most frequently consumed non-prescription drug, yet it is well known to induce toxicity. Here, we have evaluated the effects of exercise training on vascular dysfunction induced by PAR. Rats were distributed among four groups: (a) Sedentary; (b) Exercise; (c) Sedentary+PAR; and (d) Exercise+PAR. The exercise comprised swimming 50 min/d, 5 d/wk for 6 weeks (+PAR in the last 2 weeks, at 400 mg/kg/d/p.o.). After killing, the rats' blood and aortas were collected for biochemical analysis of hepatic transaminases, TBARs reaction, glutathione, glutathione reductase, SOD, and catalase. In vitro vascular relaxation was measured using acetylcholine and sodium nitroprusside in the presence or absence of tiron (an antioxidant). Vascular protein expression (eNOS and sGC) also were analysed. Increased transaminases after PAR treatment were found to be reduced by exercise. Vasodilation was impaired by PAR only in the sedentary group. Exercise prevented alterations in lipoperoxidation and glutathione levels after PAR exposure. Glutaathione reductase and SOD also were increased by PAR but were normalized in the exercised group. Catalase activity and protein expressions did not change in any group. PAR treatment caused impairment in both vasodilation and redox balance; however, exercise training prevented the vascular and redox system dysfunction induced by PAR treatment.