Pretreatment With Risperidone Ameliorates Systemic LPS-Induced Oxidative Stress in the Cortex and Hippocampus

Abstract

Risperidone (RIS), an atypical antipsychotic has been found to show anti-inflammatory effect against lipopolysaccharide (LPS)-induced inflammation. In vitro study has revealed that RIS inhibits the LPS-induced reactive oxygen species (ROS) formation. We investigated the antioxidant effects of RIS on LPS-induced oxidative stress markers in Swiss albino mice. Ten weeks old male Swiss albino mice (30 ± 2 g) were pretreated with either distilled water (control) or RIS (3 mg/kg) for 7 days. On day 8, animals were challenged with a single dose of LPS (0.8 mg/kg) while control animals received distilled water only. The animals were sacrificed after 24 h of LPS administration and tissue samples were collected. RIS administration significantly (p < 0.05) reduced the LPS-induced elevated levels of lipid peroxidation product malondialdehyde (MDA), advanced protein oxidation products, and nitric oxide (NO) in the cortex. Catalase (CAT) and superoxide dismutase (SOD) levels were also diminished while the level of glutathione (GSH) was enhanced. Hippocampus data showed that RIS significantly (p < 0.05) reduced the LPS-induced increased levels of MDA and NO, and SOD activity. Our results suggest that LPS-induced neuronal oxidative damage can be alleviated by the pretreatment with RIS and the effect is shown presumably by scavenging of the ROS by risperidone as an antioxidant.

Keywords: LPS; brain; oxidative stress; psychiatric disease; risperidone.

FIGURE 1

Effect of various treatments on the level of lipid peroxidation (MDA). Groups are Ctrl (control), LPS (lipopolysaccharide), LPS+RIS (lipopolysaccharide + risperidone), and RIS (risperidone). The level of MDA was assayed from the prefrontal cortex (A), hippocampus (B), and liver (C) tissues. Values are represented as mean ± SEM. Post hoc multiple comparison test namely, “Newman–Keuls” test was used to compare between groups. n = 6 per group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.

FIGURE 2

Effect of various treatments on the level of advanced protein oxidation products (APOPs). Groups are Ctrl (control), LPS (lipopolysaccharide), LPS+RIS (lipopolysaccharide + risperidone), and RIS (risperidone). The level of AOPP was determined from the prefrontal cortex (A), hippocampus (B), and liver (C) tissues. Values are represented as mean ± SEM. Post hoc multiple comparison test namely, “Newman–Keuls” test was used to compare between groups. n = 6 per group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.

FIGURE 3

Effect of various treatments on the level of nitric oxide (NO). Groups are Ctrl (control), LPS (lipopolysaccharide), LPS+RIS (lipopolysaccharide + risperidone), and RIS (risperidone). NO was measured from the prefrontal cortex (A), hippocampus (B), and liver (C) tissues. Values are represented as mean ± SEM. Post hoc multiple comparison test namely, “Newman–Keuls” test was used to compare between groups. n = 6 per group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001.

FIGURE 4

Effect of various treatments on the activity of catalase (CAT). Groups are Ctrl (control), LPS (lipopolysaccharide), LPS+RIS (lipopolysaccharide + risperidone), and RIS (risperidone). CAT activity was measured from the prefrontal cortex (A), hippocampus (B), and liver (C) tissues. Values are represented as mean ± SEM. Post hoc multiple comparison test namely, “Newman–Keuls” test was used to compare between groups. n = 6 per group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.

FIGURE 5

Effect of various treatments on the activity of superoxide dismutase (SOD). Groups are Ctrl (control), LPS (lipopolysaccharide), LPS+RIS (lipopolysaccharide + risperidone), and RIS (risperidone). SOD activity was measured from the prefrontal cortex (A), hippocampus (B), and liver (C) tissues. Values are represented as mean ± SEM. Post hoc multiple comparison test namely, “Newman–Keuls” test was used to compare between groups. n = 6 per group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.

FIGURE 6

Effect of various treatments on the level of glutathione (GSH). Groups are Ctrl (control), LPS (lipopolysaccharide), LPS+RIS (lipopolysaccharide + risperidone), and RIS (risperidone). GSH was measured from the prefrontal cortex (A), hippocampus (B), and liver (C) tissues. Values are represented as mean ± SEM. Post hoc multiple comparison test namely, “Newman–Keuls” test was used to compare between groups. n = 6 per group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.