title: Maternally administered lipopolysaccharide (LPS) upregulates the expression of heme oxygenase-1 in fetal liver: the role of reactive oxygen species.
abstract: 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 microg/kg) on gestational day 17. Results showed that the expression of HO-1 in fetal liver was increased, beginning 2h after LPS, being at the highest level 24h after LPS, and remaining elevated up to 48h after LPS, whereas HO-2, the constitutive form, did not change at the various time points observed. LPS-induced upregulation of HO-1 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.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xiang-Yun
authors.initials: XY
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Wang
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Ji
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008813:Mice, Inbred ICR; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: D003497:Cyclic N-Oxides; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C029217:phenyl-N-tert-butylnitrone; D051547:Heme Oxygenase-1; D005978:Glutathione