1a) without infiltration of inflammatory mononuclear cells. Hepatic triglyceride content was measured to quantify the degree of steatosis. The triglyceride click here content was significantly greater in OVX transgenic mice than in mice in the other three groups (Fig. 1b),

which was consistent with the results for hepatic steatosis. Thus, the increase in the serum ALT level in the OVX transgenic mice was thought to reflect the hepatic steatosis. Only OVX transgenic mice showed marked hepatic steatosis, regardless of the comparable diet intake and the ratio of liver to bodyweight of OVX non-transgenic mice (Table 1). We have previously demonstrated that iron-overloaded male FL-N/35 transgenic mice expressing the HCV polyprotein develop severe hepatic steatosis AG-014699 in vitro through increased ROS production.[11] Therefore, we examined

whether ROS production was relevant to the marked hepatic steatosis observed in the OVX transgenic mice. Ovariectomy significantly increased ROS (superoxide) production in both transgenic mice and non-transgenic mice, but the level of ROS production was greater in the OVX transgenic mice than in the OVX non-transgenic mice (Fig. 2). We next measured inflammatory cytokine levels in the liver. Ovariectomy significantly increased hepatic expression of IL-6 mRNA to the same degree in both transgenic mice and non-transgenic mice (Fig. 3). This ovariectomy-induced increase in hepatic IL-6 mRNA was consistent with the results of a previous report that OVX mice produced more hepatic IL-6 than non-OVX mice after chemically induced liver injury.[5] There also was a trend for increase in TNF-α and IL-1β mRNA expression after ovariectomy in both the transgenic mice and non-transgenic mice, but their increases did not reach statistical significance, probably because of the large deviation (Fig. 3). These results suggested that inflammatory

cytokines were unlikely to be associated with greater ROS production in OVX transgenic mice than in OVX non-transgenic mice. We previously reported that male medchemexpress FL-N/35 transgenic mice developed hepatic iron accumulation through the reduced transcription of hepcidin,[18] a negative regulator in iron homeostasis.[21, 22] Excess divalent iron can be highly toxic, mainly via the Fenton reaction producing hydroxyl radicals.[23] Therefore, we measured hepatic iron content to assess whether greater ROS production resulted from increased hepatic iron accumulation in OVX transgenic mice. Unexpectedly, ovariectomy significantly decreased hepatic iron content to the same degree in both transgenic mice and non-transgenic mice (Fig. 4a). These results are potentially explained by significantly increased transcription of hepcidin after ovariectomy (Fig. 4b).