Effects of NF-κB inhibitor pyrrolidine dithiocarbamate on the early-stage acute lung injury induced by paraquat

Abstract

Objective To determine the effects of pyrrolidine dithiocarbamate(PDTC),a nuclear factor-κB (NF-κB) inhibitor,on paraquat-induced early-stage acute lung injury.Methods Following establishment of paraquat-induced lung injury mice model,64 adult male SD rats were randomly divided into PQ+PBS gioup (32 SD rats were treated with phosphate buffer solution) and PQ+PDTC group (32 SD rats were treatecl with 100 mg/kg PDTC).The survival rate of two groups was assessed at hours 24,48 and 72 respectively.Haematoxylin-eosin staining was employed to assess the acute lung injury for scoring,and immunochemical assay was used to detect inflammatory cell infiltration in the lungs.The level of TNF-α and IL-6 was measured by enzyme-linked immunosorbent assay and activation of NF-κB in the lungs was assessed by using Western blotting.Results PDTC improved the survival rate at 72 hours as compared with group PQ+PBS[24/32(75％) in group PQ+PDTC vs 13/32(40.6%) in group PQ+PBS,P=0.015] and acute lung injury score at 24 hours (7.5±1.0 vs 9.8±1.5),48 hours (9.7±0.8 vs 12.0±0.9) and 72 hours (11.5±1.0 vs 14.5±1.0) (all P＜0.05).PDTC resulted in reduced cell count with myeloperoxidase expression,the levels of TNF-α and IL-6 in the lungs and the protein levels of NF-κB in the nucleus and cytoplasm (all P＜0.05).Conclusion PDTC reduces early-stage mortality of acute lung injury by suppressing infiltration of myeloperoxidase-positive inflammatory cells and inhibiting NF-κB activation leading to decreased TNF-α and IL-6 expression in the lungs. Key words: Paraquat; Respiratory distress syndrome, adult; NF-kappa B; Pyrrolidine dithiocarbamate