The aim of this study was to evaluate and compare the effectiveness of
N-acetylcysteine (NAC) and liposomally-encapsulated NAC (
L-NAC) in ameliorating the hepatotoxic effects of
lipopolysaccharide (LPS). LPS, a major cell wall molecule of Gram-negative bacteria and the principal initiator of
septic shock, causes liver injury in vivo that is dependent on neutrophils, platelets, and several inflammatory mediators, including tumour
necrosis factor-alpha (
TNF-alpha). Male Sprague-Dawley rats were pretreated intravenously with saline, plain
liposomes (
dipalmitoylphosphatidylcholine [DPPC]), NAC (25 mg/kg
body weight), or
L-NAC (25 mg/kg NAC
body weight) and 4 h later were challenged intravenously with LPS (Escherichia coli O111:B4, 1.0 mg/kg
body weight); animals were killed 20 h post-LPS challenge. Hepatic cell injury was evaluated by measuring the
alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) activities in plasma. LPS-induced activation of the inflammatory response was evaluated by measuring the levels of
myeloperoxidase activity and
chloramine concentration in liver homogenates as well as
TNF-alpha levels in plasma. The hepatic levels of lipid peroxidation products and non-
protein thiols (NPSH) were used to assess the extent of involvement of oxidative stress mechanisms. In general, challenge of animals with LPS resulted in hepatic
injuries, activation of the inflammatory response, decreases in NPSH levels and increases in the levels of lipid peroxidation products (
malondialdehyde and 4-hydroxyalkenals). Pretreatment of animals with NAC or empty
liposomes did not have any significant protective effect against LPS-induced hepatotoxicity. On the other hand, pretreatment of animals with an equivalent dose of
L-NAC conferred protection against the liver
injuries induced following LPS challenge. These data suggest that NAC when delivered as a liposomal formulation is a potentially more effective prophylactic pharmacological agent in alleviating LPS-induced liver
injuries.