Modulation of oxidative and inflammatory cardiac response by nonselective 1-and 2-cyclooxygenase inhibitor and benznidazole in mice

ObjectivesThis study investigated the combined effects of benznidazole (BZ) and ibuprofen (IB) on the oxidative and inflammatory status of the cardiac tissue in vivo. MethodsSwiss mice were randomized in groups receiving BZ (100mg/kg) and IB (400mg/kg) alone or combined (BZ+IB 200 or 400mg/kg). Control animals were concurrently treated with 1% carboxymethyl cellulose. All treatments were administered orally for 7 days. Key findingsBZ treatment increased cardiac production of nitrogen/oxygen-reactive species, malondialdeyde, carbonyl proteins, prostaglandins as well as the activities of catalase, superoxide dismutase and glutathione peroxidase. These parameters were attenuated by IB, with the best results at higher dose. Individually, BZ and IB significantly reduced the tissue levels of chemokine ligand 2, tumour necrosis factor- and IL-10, but no reduction was observed when the treatments were combined. ConclusionsBZ triggers an oxidative and nitrosative route, which is associated with increased prostaglandin synthesis and marked damages to the lipids and proteins of the cardiac tissue. IB treatment attenuated reactive stresses triggered by BZ, which was an independent effects of this drug on the endogenous antioxidant enzymes. Individually, but not together, BZ and IB reduced the cardiac inflammatory status, indicating a beneficial and complex drug interaction.