Contribution of MEK1/ERK1/2/iNOS Pathway to Oxidative Stress and Decreased Caspase-3 Activity in Endotoxemic Rats

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)

Volume 16, 3 Issues, 2017

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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Claudiu T. Supuran
Neurofarba Department
University of Florence

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Contribution of MEK1/ERK1/2/iNOS Pathway to Oxidative Stress and Decreased Caspase-3 Activity in Endotoxemic Rats

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 11(3): 243-252.

Author(s): Belma Korkmaz, Tuba Cuez, C. Kemal Buharalioglu, Abdullah T. Demiryurek, Seyhan Sahan-Firat, A. Nihal Sari and Bahar Tunctan.

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Yenisehir Campus, Mersin University, Mersin, 33169, Turkey.


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.


Apoptosis, endotoxin, ERK1/2, iNOS, MEK1, oxidative stress.

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Article Details

Volume: 11
Issue Number: 3
First Page: 243
Last Page: 252
Page Count: 10
DOI: 10.2174/1871523011202030243
Price: $58

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