title: Contribution of MEK1/ERK1/2/iNOS pathway to oxidative stress and decreased caspase-3 activity in endotoxemic rats.
abstract: Oxidative stress and apoptosis are the states that can contribute to the pathogenesis of sepsis. In this study we aimed to investigate whether mitogen-activated protein kinase kinase 1 (MEK1)/extracellular signal-regulated kinase 1/2 (ERK1/2)/inducible nitric oxide synthase (iNOS) pathway plays a role in oxidative stress and apoptosis in endotoxemic rats. Systemic total antioxidant, SOD, GPx, and GR activities as markers of oxidative stress, and tissue caspase-3 enzyme activity as a marker of apoptosis were measured in sera and thoracic aortae of male Wistar rats sacrificed 4 h after being treated with saline (vehicle) or lipopolysaccharide (LPS) (10 mg/kg, i.p.). A decrease in total antioxidant activity and caspase-3, SOD, GPx, and GR enzyme activities was occured by LPS. These changes caused by LPS were prevented when a selective iNOS inhibitor, 1,3-PBIT (10 mg/kg, i.p.) or a selective inhibitor of ERK1/2 phosphorylation by MEK1, U0126 (5 mg/kg, i.p.) were given 1 h after administration of LPS. Our results suggest that decreased activity of MEK1/ERK1/2/iNOS pathway prevents oxidative stress by increasing systemic antioxidant enzyme activities and restores decreased caspase-3 activity in thoracic aorta in endotoxemic rat.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Yenisehir Campus, Mersin University, Mersin, 33169, Turkey. belmakorkmaz@yahoo.com
authors.forename: Belma
authors.initials: B
authors.lastname: Korkmaz
authors.forename: Tuba
authors.initials: T
authors.lastname: Cuez
authors.forename: C Kemal
authors.initials: CK
authors.lastname: Buharalioglu
authors.forename: Abdullah T
authors.initials: AT
authors.lastname: Demiryurek
authors.forename: Seyhan
authors.initials: S
authors.lastname: Sahan-Firat
authors.forename: A Nihal
authors.initials: AN
authors.lastname: Sari
authors.forename: Bahar
authors.initials: B
authors.lastname: Tunctan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001013:Aorta, Thoracic; D017209:Apoptosis / Q000502:physiology; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism*; D019446:Endotoxemia / Q000201:enzymology*; D004731:Endotoxins / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D048369:MAP Kinase Kinase 1 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002070:Butadienes; D004731:Endotoxins; D004791:Enzyme Inhibitors; D009570:Nitriles; C118852:S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea; C113580:U 0126; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D053148:Caspase 3; D013890:Thiourea