Effect of ketamine on oxidative stress following lipopolysaccharide administration

The aim of this study was to determine the effect of ketamine on oxidative stress and inflammation in the brain and liver in basal state and during systemic inflammation induced by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration. Rats were treated with subcutaneous ketamine (15 or 30 mg/kg) alone, LPS (300 μg/kg, i.p.) or with ketamine (30 mg/kg) and LPS (300 μg/kg, i.p.) and euthanized 4 h later. Lipid peroxidation (malondialdehyde: MDA), reduced glutathione (GSH), nitric oxide (nitrite) concentrations and paraoxonase 1 (PON1) activity were measured in the brain (in the striatum and in the cerebral cortex) and liver. Tumour necrosis factor alpha (TNF-α) was determined in brain tissue. Histopathological assessment and immunohistochemical expression of the apoptotic marker caspase-3 were performed as well. Results: LPS increased oxidative stress in both the brain and liver tissue. Rats treated with ketamine alone exhibited higher MDA concentrations in the brain and liver, whereas brain and liver GSH and nitric oxide concentrations and PON1 activities were depressed compared with the saline control group. Ketamine given to LPS-treated rats resulted in increased MDA compared with either agent alone. GSH concentrations and PON1 activities were markedly depressed in rats given ketamine and LPS. Ketamine decreased the LPS-induced elevation in nitric oxide. Ketamine resulted in increased TNF-α in brain in saline-treated rats and increased LPS-induced TNF-α production. Ketamine resulted in minimal histological damage in cortex, striatum and liver. In rats given ketamine and LPS, both brain injury and liver damage as well as the expression caspase-3 due to endotoxin were increased. Thus, ketamine increased oxidative stress in brain and liver and the release of TNF-α in brain and enhanced the tissue injury during systemic inflammation.