The effect of different antidepressant drugs on oxidative stress after lipopolysaccharide administration in mice

Abstract

This study investigated the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine, sertraline, fluvoxamine and the tricyclic antidepressant (TCA) impiramine on oxidative stress in brain and liver induced by lipopolysaccharide administration in mice. Each drug was administered subcutaneously at doses of 10 or 20 mg/kg, for two days prior to intraperitoneal (i.p.) administration of lipopolysaccharide E (LPS: 200 µg/kg). 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. Results: The administration of lipopolysaccharide increased oxidative stress in brain and liver; it increased brain MDA by 36.1 and liver MDA by 159.8 %. GSH decreased by 34.1 % and 64.8 % and nitric oxide increased by 78.7 % and 103.8 % in brain and liver, respectively. In brain, MDA decreased after the administration of sertraline and by the lower dose of fluoxetine or fluvoxamine, but increased after the higher dose of imipramine. Reduced glutathione increased after sertraline, fluvoxamine and the lower dose of fluoxetine or imipramine. Nitric oxide decreased by sertraline, fluoxetine, fluvoxamine and by the lower dose of imipramine. In the liver, all drugs decreased MDA and increased GSH level. Nitric oxide is decreased by sertraline, fluvoxamine and by the lower dose of fluoxetine or imipramine. It is concluded that, during mild systemic inflammatory illness induced by peripheral bacterial endotoxin injection, the SSRIs fluoxetine, sertraline and fluvoxamine reduced, while the TCA impiramine increased oxidative stress induced in the brain. The SSRIs as well as imipramine reduced oxidative stress due to lipopolysaccharide in liver tissue.

Keywords: antidepressant drugs; brain; lipopolysaccharide; liver; mice; oxidative stress.

Figure 1. Effect of antidepressant drugs on the brain tissue level of malondialdehyde (MDA; nmol/g tissue) in lipopolysaccharide-treated mice. The plus sign indicates significant change from the saline group. Asterisks indicate significant change from saline group and between different groups as indicated.

Figure 2. Effect of antidepressant drugs on the brain tissue level of reduced glutathione (GSH: µmol/g tissue) in lipopolysaccharide-treated mice. The plus sign indicates significant change from the saline group. Asterisks indicate significant change from saline group and between different groups as indicated.

Figure 3. Effect of antidepressant drugs on the brain tissue level of nitric oxide (nitrite/nitrate; µmol/g tissue) in lipopolysaccharide-treated mice. The plus sign indicates significant change from the saline group. Asterisks indicate significant change from saline group and between different groups as indicated.

Figure 4. Effect of antidepressant drugs on the liver tissue level of malondialdehyde (MDA; nmol/g tissue) in lipopolysaccharide-treated mice. The plus sign indicates significant change from the saline group. Asterisks indicate significant change from saline group and between different groups as indicated.

Figure 5. Effect of antidepressant drugs on the liver tissue level of reduced glutathione (GSH: µmol/g tissue) in lipopolysaccharide-treated mice. The plus sign indicates significant change from the saline group. Asterisks indicate significant change from saline group and between different groups as indicated.

Figure 6. Effect of antidepressant drugs on the liver tissue level of nitric oxide (nitrite/nitrate; µmol/g tissue) in lipopolysaccharide-treated mice. The plus sign indicates significant change from the saline group. Asterisks indicate significant change from saline group and between different groups as indicated.