科研之友
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摘要
Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the rate-limiting step in the degradation of heme to biliverdin, carbon monoxide and iron. Previous studies have demonstrated that lipopolysaccharide (LPS) upregulates the expression of HO-1 in adult mouse liver. The present study aimed to investigate the effects of maternal LPS exposure on the expression of HO-1 in fetal liver. The pregnant mice were intraperitoneally injected with different doses of LPS (1, 10, 75 mu g/kg) on gestational day 17. Results showed that the expression of HO-1 in fetal liver was increased, beginning 2 h after LPS, being at the highest level 24 h after LPS, and remaining elevated up to 48 It after LPS, whereas HO-2, the constitutive form, did not change at the various time points observed. LPS-induced upregulation of HO-I was blocked by alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Correspondingly, PBN pretreatment significantly attenuated LPS-induced lipid peroxidation and glutathione (GSH) depletion in fetal liver. However, aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and pentoxifylline (PTX), an inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, had no effect on LPS-induced upregulation of HO-1 in fetal liver. In conclusion, reactive oxygen species (ROS), rather than TNF-alpha or nitric oxide (NO), are involved in LPS-induced upregulation of HO-1 in fetal liver. These results provide new evidence that maternal LPS exposure results in oxidative stress in fetuses, which may contribute to LPS-induced developmental toxicity.
- 出版日期2008-2-15
- 单位安徽医科大学
