Genotype effects on the antioxidant enzymes activity and mRNA expression in liver and kidney tissues of autoimmune-prone MRL/McJ-lpr/lpr mice

Abstract

Congeneic pairs of MKL/lpr and MRL/ + +(+ / +) mice differ in incidence of autoantibodies, lymphoproliferative disease and survival, characteristics that are linked to immunological abnormalities. MRL/lpr mice have a significantly shorter life span compared to +/+ mice. Because a weak antioxidant defense and an increased generation of free radicals are generally implicated in the severity of many autoimmune diseases, the present study was undertaken to compare the influence of genotype on lipid composition, lipid peroxidation and expression of mRNA, and activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and Superoxide dismutase (SOD) in the livers and kidneys of these mice. The expression of SOD, GSH-Px and CAT mRNAs was significantly higher ( P < 0.05) in the livers of + / + mice, while in the kidneys only SOD expression was found significantly higher in + / + mice when compared to MRL/ lpr mice. Further, the activity of cytosolic SOD and GSH-Px was also found significantly higher ( P < 0.001) in the livers of + / + mice. Both livers and kidneys of MRL/ lpr mice exhibited significantly higher levels of arachidonic acid (20:4( n − 6)), significantly higher generation of thiobarbituric acid reactive substances (TBARS) and higher estimated peroxidation index than the + / + mice. In addition, the MRL/ lpr mice had higher levels of serum anti-cardiolipin antibodies. In summary, the results from the present study indicate that besides several immune-related abnormalities, the MRL/lpr mice may exhibit their inability to cope with oxidative stress due to a poor antioxidant defense system. This weak defense system is revealed by lower mRNA expression of antioxidant enzymes, weak SOD and GSH-Px enzyme activities, and an increased level of 20:4( n − 6) in liver lipids, which in turn may increase generation of free radicals in the livers and kidneys, thus making the MRL/lpr mice more susceptible to autoimmune disease than the + / + mice.