Effect of ketamine on oxidative stress following lipopolysaccharide administration

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.

Long-Term Treatment with Fluvoxamine Decreases Nonmotor Symptoms and Dopamine Depletion in a Postnatal Stress Rat Model of Parkinson’s Disease

“…In fact, we found that all Fluvoxamine-treated rats did not show a preference for the use of the left forelimb (unimpaired) in the cylinder test suggesting a reduced toxic effect of the neurotoxin 6-OHDA due to the treatment. This major finding agreed with results from previous studies that showed that antidepressants can reduce MDA levels thereby significantly protecting striatal, prefrontal, and hippocampal cells and preventing neuronal loss associated with both chronic stress and 6-OHDA neurotoxicity [83][84][85][86][87]. We, therefore, postulated that Fluvoxamine possesses antioxidant properties (responsible for mopping up the free radicals generated by the autooxidation of 6-OHDA) and antitoxicity potential that reduced 6-OHDA neurotoxicity.…”

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice

“…An important finding of our study consists in the lack of significant differences in cortical amounts of antioxidant enzymes between early ketamine-treated mice and controls. This result might appear contrasting with preclinical evidence describing, instead, a decreased activity of SOD and CAT in the PFC of ketamine-treated rats ( de Oliveira et al, 2009 ), as well as a reduction of GSH concentration ( Abdel-Salam et al, 2015 ). However, in these previously published studies, ketamine exposure occurred in adult life.…”

Significance of malondialdehyde, superoxide dismutase and endotoxin levels in Budd‑Chiari syndrome in patients and a rat model

“…In the present study, the ET levels in the liver homogenate and serum of BCS rats was positively correlated with MDA levels and negatively correlated with SOD levels, suggesting that ET may damage the liver through OS, which is supported by the results of studies on other types of liver injury ( 16 ). This is due to ligation of the IVC posterior to the liver resulting in an obstruction of outflow from the hepatic veins and IVC, leading to hepatic congestion and hypoxia, resulting in the production of a large number of ROS, which may activate hypoxia-inducible factor (HIF)-1, nuclear factor (NF)-κB, and various cytokines, consequently activating HSC to cause hepatic fibrosis ( 22 ).…”

“…When hepatic congestion occurs, intestinal ET enters the portal vein ectopically ( 14 , 15 ). Early studies have reported that ET participates in liver congestion injury ( 16 , 17 ). According to the present hypothesis, OS also has an important role in BCS, but studies to evidence this are currently lacking.…”