[24] These results suggested that hepatic iron content was not related to greater ROS production in OVX transgenic mice than in OVX non-transgenic

mice. The increase in inflammatory cytokine production and the hepatic iron content after ovariectomy were comparable in transgenic and non-transgenic mice. Nevertheless, the serum ALT level, hepatic steatosis and ROS production were greater in OVX transgenic mice than in OVX non-transgenic mice. Therefore we measured dROM and BAP in serum to compare antioxidant potentials in OVX transgenic and OVX non-transgenic DNA Damage inhibitor mice. We confirmed the significant negative correlation between the ratio of BAP to dROM and hepatic content of superoxide (Fig. 5). As expected, the values for

dROM were higher in OVX mice than in sham-operated mice, regardless of whether they were transgenic or non-transgenic. However, Selleck Raf inhibitor a significant increase in the BAP value was found in OVX non-transgenic mice but not in OVX transgenic mice, which resulted in a lower ratio of BAP to dROM in the OVX transgenic mice than in the OVX non-transgenic mice (Table 2). The first line of defense against ROS is the detoxifying enzymes that scavenge ROS. These include SOD and GPx1. Therefore we next investigated the expression levels of SOD2 and GPx1. The hepatic expression levels of SOD2 mRNA and GPx1 mRNA were significantly greater in OVX non-transgenic mice than in sham-operated non-transgenic mice, but

were comparable in OVX transgenic mice and sham-operated transgenic mice (Fig. 6a). Western blot analysis of the hepatic mitochondria fractions also showed significant increases of SOD2 and GPx1 expression in OVX non-transgenic mice but not in OVX transgenic mice (Fig. 6b). These results suggested that antioxidant defense mechanisms may be induced against ovariectomy-related ROS production in non-transgenic mice but not in transgenic mice. Proliferator-activated receptor-γ co-activator-1α is a master regulator of mitochondrial biogenesis medchemexpress and respiration[25] and required for the induction of many ROS-detoxifying enzymes, including SOD2 and GPx1 upon oxidative stress.[26] SIRT3 is a member of a class III histone deacetylase and is reported to mediate PGC-1α-dependent induction of ROS-detoxifying enzymes.[27] In accordance with the changes in SOD2 and GPx1 levels after ovariectomy, the hepatic expression of SIRT3 mRNA was significantly greater in OVX non-transgenic mice than in sham-operated non-transgenic mice, but comparable in OVX transgenic mice and sham-operated transgenic mice (Fig. 7a). Western blot analysis of hepatic mitochondria showed a significant increase of SIRT3 expression in OVX non-transgenic mice but not in OVX transgenic mice (Fig. 7a).