Lipopolysaccharide-induced oxidative stress in the liver: comparison between rat and rabbit

In the present study the effect of LPS on biochemical systems involved in radical formation and scavenging processes in tissues from rabbit (LPS-sensitive) and rat (LPS-resistant) was investigated. The results obtained show a significant enhancement in the endogenous antioxidative enzyme system in rats as a result of LPS injection. In rats, 24 h after LPS injection, glutathione peroxidase (G-POX) and superoxide dismutase (SOD) activities were increased by 60% and 120%, respectively, compared to the control. However, in rabbits the increase in these activities was relatively mild. Moreover, NADPH-oxidase activity, which produces superoxide radical, was increased about twofold in rabbit, 15 h following LPS injection. In rats, injection of LPS did not result in any significant changes in the activity of this enzyme. In rats, a decrease in malonaldehyde (MDA) levels appeared after injection of LPS, while in contradistinction, the peroxidative levels of lipids in the rabbit's liver were increased about 3-fold. Injection of D-galactosamine (Gal-N) in combination with LPS significantly increased the sensitivity of rats to LPS characterized by a significant increase in NADPH-oxidase activity. This study indicates that one possible mechanism (among others) that may explain the relative sensitivity of rabbits compared to rat, may be related to the increase in the production of reactive oxygen substances (ROS) which is not accompanied by a concomitant increase of the protective antioxidative enzymes. Furthermore, the relative resistance of the rat was found to be related to an increase in the activity of the protective antioxidative systems following administration of LPS.