Protective effect of pyrrolidine dithiocarbamate pretreatment on myocardium against LPS-induced injury in rats

Abstract

Objective To investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) pretreatment on lung agaillst LPS-indueed injury in rats.Methods Fifty-four Wistar rats of both sexes weighing 180-220 g were randomly idivided into 3 groups:group I normal control(group C,n=6);group Ⅱ LPS (group L,n=24)and group Ⅲ PDTC(group P,n=24).Endotoxemia was induced by intraperitoneal LPS 8 mg/kg in group Ⅱ and Ⅲ.In group Ⅲ PDTC 120 mg/kg was injected iv at 30 min before IP LPS.Venous blood samples were collected at 1,3,6 and 12 h after LPS administration in group L and P and after normal saline administration in group C for determination of serum IL-6 concentration by ELISA.Six animals were killed at each time point after blood sample collection.The lungs were removed for microscopic examination and determination of W/D lung weight ratio,HSP70 expression and NF-κB activity.Results Intraperitoneal LPS significantly increased serum IL-6 concentration and W/D lung weight ratio,HSP70 expression and NF-κB activity in group Ⅱ.PDTC pretreatment significantly attenuated LPS-induced increase in serum IL-6 concentration,W/D lung weight ratio andNF-κB activity.The lung histologic dalnage induced by LPS Wag also ameliorated by pretreatment with PDTC.Conclusion Pyrrolidine dithiocarbamate pretreatment Can protect lung against LPS-induced injury through inhibition of activation of lung tissue NF-κB and up-regulation of expression of HSP70. Key words: Pyrrolidines; Thiocarbamates; Endotoxins; Respiratory distress syndrome,adult