insight into the possible protective effect of pyrrolidine dithiocarbamate against lipopolysaccharide- induced oxidative stress and acute hepatic injury in rats

ABSTRACT

Lipopolysaccharide [LPS] is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several toxic metabolites, such as reactive oxygen species. In this study, the effect of pyrrolidine dithiocarbamate [PDTC], an antioxidant with nuclear factor- kappa B inhibitor activity, was evaluated in LPS-induced oxidative stress and acute hepatic injury in rats. Animals were pre-treated for 3 consecutive days with PDTC[200 mg/kg/day, i.p.] or saline and animals were then challenged with LPS[6 mg/kg, i.p.] or saline. Six hours after LPS injection, animals were decapitated and blood and liver samples were collected to assess the chosen biochemical parameters. Saline-pretreated animals challenged with LPS revealed extensive liver damage, as evidenced by increase in serum levels of alanine aminotransferase [ALT], aspirate aminotransferase [AST] and gamma glutamyl transferase [gamma -GT]. Also, LPS treatment resulted in significant increases in serum lactate dehydrogenase [LDH], tumor necrosis factor-alpha [TNF- alpha] and nitrite levels. Furthermore, LPS challenge caused oxidative stress as indicated by an increase in hepatic lipid peroxidation measured as thiobarbituric acid reactive substances [TBARS] and a decrease in hepatic reduced glutathione concentration [GSH] as well as decreased activities of superoxide dismutase [SOD] and [GSH] as well as decreased activities of superoxide dismutase [SOD] and catalase in hepatic tissues. The administration of PDTC prior to LPS challenge resulted in improved liver functions as evidenced by the decline in serum AST, ALT, gamma-GT levels and reduction in serum LDH, TNF- alpha and nitrite levels. Moreover, PDTC reduced the chosen lipid peroxidation marker, TBARS and increased GSH concentration, and SOD and catalase activities in hepatic tissues. These results indicate that PDTC may be a useful pharmacological agent in alleviating LPS-induced oxidative stress and acute hepatic injury