title: Cerium oxide nanoparticles alleviate oxidative stress and decreases Nrf-2/HO-1 in D-GALN/LPS induced hepatotoxicity.
abstract: Translocation of the master regulator of antioxidant-response element-driven antioxidant gene, nuclear factor erythroid 2 (Nrf-2) from the cytoplasm into the nucleus and triggering the transcription of hemoxygenase-1 (HO-1) to counteract the oxidative stress is a key feature in D-galactoseamine and lipopolysaccharide (D-GALN/LPS) induced hepatotoxicity. We mainly aimed to study the effect of cerium oxide (CeO2) nanoparticles on Nrf-2/HO-1 pathway whereas; it has previously shown to have an antioxidant effect in liver models. Administration of CeO2 nanoparticles significantly decreased the translocation of the cytoplasmic Nrf-2 with a concomitant decrement in the gene expression of HO-1 as it reveals a powerful antioxidative effect as indicated by the significant increase in the levels of glutathione (GSH), glutathione peroxidase (GPX1), glutathione reductase (GR), superoxide dismutase (SOD) and catalase. In synchronization, a substantial decrement in the levels of inducible nitric oxide synthase (iNOS), TBARS and percentage of DNA fragmentation was established. These results were confirmed by histopathology examination which showed a severe degeneration, haemorrhages, widened sinusoids and focal leukocyte infiltration in D-GALN/LPS treatment and these features were alleviated with CeO2 administration. In conclusion, CeO2 is a potential antioxidant that can effectively decrease the translocation of the cytoplasmic Nrf-2 into the nucleus and decrease HO-1 in D-GALN/LPS induced hepatotoxicity.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt.
authors.forename: Reem M
authors.initials: RM
authors.lastname: Hashem
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Laila A
authors.initials: LA
authors.lastname: Rashd
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Beni Suef University, Beni Suef, Egypt.
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Hashem
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt. Electronic address: hatemmsoliman@gmail.com.
authors.forename: Hatem M
authors.initials: HM
authors.lastname: Soliman
mesh_terms: D000818:Animals; D002563:Cerium / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D005688:Galactosamine / Q000633:toxicity*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D053768:Metal Nanoparticles / Q000627:therapeutic use; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D002563:Cerium; C030583:ceric oxide; D005688:Galactosamine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Cerium oxide nanoparticles; D-galactoseamine; HO-1; Hepatotoxicity; Lipopolysaccharide; Nrf-2