title: The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice.
abstract: The effects of trimetazidine, a novel anti-ischemic agent, on the development of oxidative stress induced in mice with lipopolysaccharide endotoxin were investigated. The drug was administered orally once daily at doses of 1.8, 3.6 or 7.2 mg/kg for two days prior to intraperitoneal (i.p.) injection of lipopolysaccharide E (200 μg/kg) and at time of endotoxin administration. Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. The administration of lipopolysaccharide increased oxidative stress in both the brain and liver tissue. MDA increased by 33.9 and 107.1 %, GSH decreased by 23.9 and 84.3 % and nitric oxide increased 70.3 and 48.4 % in the brain and liver, respectively. Compared with the lipopolysaccharide control group, brain MDA decreased by 26.2 and 36.7 %, while GSH increased by 18.2 and 25.8 % after the administration of trimetazidine at 3.6 and 7.2 mg/kg, respectively. Brain nitric oxide decreased by 45.3, 50.8 and 57.0 % by trimetazidine at 1.8, 3.6 and 7.2 mg/kg, respectively. In the liver, MDA decreased by 18.7, 30.7 and 49.4 % and GSH increased by 150.3, 204.8 and 335.4 % following trimetazidine administration at 1.8, 3.6 and 7.2 mg/kg. Meanwhile, nitric oxide decreased by 17.3 % by 7.2 mg/kg of trimetazidine. These results indicate that administration of trimetazidine in the presence of mild systemic inflammatory response alleviates oxidative stress in the brain and liver.
authors.affiliation: Department of Toxicology and Narcotics, National Research Centre, Cairo.
authors.forename: Omar M E
authors.initials: OM
authors.lastname: Abdel-Salam
authors.affiliation: Department of Medical Biochemistry, National Research Centre, Cairo.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Mohammed
authors.affiliation: Department of Pharmacology, National Research Centre, Cairo.
authors.forename: Amany A
authors.initials: AA
authors.lastname: Sleem
keywords: lipopolysaccharide; mice; oxidative stress; trimetazidine