Effect of resveratrol and tetracycline on the subacute paraquat toxicity in mice.

Abstract

Paraquat (PQ) is a nonselective bipyridyl herbicide widely used in agriculture to control weeds, but its accidental, occupational, or intentional exposure in humans is known to cause pneumo- and neurotoxicity which may proves fatal. Oxidative stress is reported as an underlined mechanism of PQ-induced toxicity in alveolar cells, neurons, and astroglia. PQ generates superoxides both through electron transport reaction (ETC) with nicotinamide adenine dinucleotide-dependent oxidoreductase and by the redox cycling via reaction with molecular oxygen. In lungs, it causes edema and inflammation resulting in neutrophils infiltration and subsequent activation of pro-inflammatory cytokines. In the present study, toxicity of subacute oral PQ exposure and effect of resveratrol (Res) and/or tetracycline (TC) on oxidative stress and inflammatory markers in lungs, brain, and liver was studied. Levels of glutathione and malondialdehyde and activities of myeloperoxidase, glutathione peroxidase, and catalase were measured in lungs, brain, and liver. PQ interferes in the function of mitochondrial ETC complexes causing decreased adenosine triphosphate levels, and hence the activities of complexes I and IV were studied in brain tissues. Res, a natural antioxidant, and TC, an antibiotic with its antimicrobial and anti-inflammatory properties, offered significant protection from severe oxidative stress and inflammation and ameliorated the general well-being of mice against the toxic outcome of PQ.