Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model.

Abstract

Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. Female Sprague-Dawley rats (n=24) were allocated into three groups: sham, PQ and PQ+3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15mg/kg PQ intraperitoneally in PQ and PQ+3-AB groups. 3-AB (10mg/kg twice per day) was administered to the PQ+3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-β) levels and histological injury scores in the PQ+3-AB group were significantly lower than in the PQ group (P<0.05, PQ vs. PQ+3-AB). Total antioxidant capacity in the PQ+3-AB group was significantly higher than in the PQ group (P<0.05, PQ+3-AB vs. PQ). Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.