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چکیده
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Introduction: Oxidative stress plays a key role in the pathophysiology of schizophrenia, a debilitating mental illness. Silymarin (SM) is a flavonoid with antioxidant properties found in Silybum marianum. However, the bioavailability of SM is rather low due to poor water solubility. The purpose of this study was to investigate the effect of neuroprotective of silymarin-loaded chitosan nanoparticles (SM-CS-NPs) on ketamine-induced cognitive disorders and hippocampal oxidative damages. Materials and Methods: In this study, 35 male mice were divided into five groups; control and four ketamin groups treated with saline, aripiprazole, SM, and SM-CS-NPs at doses of 20 mg/kg/30 days, respectively. In the experimental groups, animals received ketamine (20 mg/kg/day) from the 16th to the 30th day intraperitoneally. Cognitive deficits were evaluated employing a novel object recognition test (NORT). Furthermore, various oxidative stress markers in the hippocampal area were assessed. Results: Our results revealed that ketamine significantly reduced the discrimination index and catalase, superoxide dismutase, and glutathione reductase enzyme activity compared with the control group. Moreover, treatment with SM and SM-CS-NPs reduced cognitive impairments, increased the activity of the antioxidant enzymes catalase, superoxide dismutase as well as glutathione reductase, and reduced malondialdehyde levels in the treatment groups. Conclusion: SM-CS-NPs may improve SM bioavailability and exert stronger neuroprotective effects against ketamine-induced cognitive deficits and hippocampal oxidative damages. s
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