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

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

Atelectasis Induced by Thoracotomy Causes Lung Injury during Mechanical Ventilation in Endotoxemic Rats

Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression.

Alteraçöes imunológicas na icterícia obstrutiva / Immunological alterations in obstructive jaundice

Pacientes com icterícia obstrutiva apresentam maior índice de complicaçöes perioperatórias, dentre as quais uma das principais é a sepsis. Parece que existe depressäo do sistema imune nesses paciente, decorrente de múltiplos fatores, entre eles a endotoxemia. Neste artigo, estäo abordadas as alteraçöes imunológicas encontradas na obstruçäo biliar, sob três aspectos: (i) a ausência de bile na luz intestinal, (ii) a obstruçäo do fluxo biliar e (iii) o acúmulo de substâncias tóxicas. Cuidados intensivos perioperatórios têm permitido a reduçäo da mortalidade nas últimas décadas, mas estratégias para reduzir a morbidade continuam sendo estudadas.