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Evaluation of cerebral and hepatic oxidative metabolism by administration of risperidone in a subacute model in rats (Rattus norvegicus)

Salcedo-Valdez, L.; Suarez-Cunza, S.

2025-07-29 biochemistry
10.1101/2025.07.14.664632 bioRxiv
Show abstract

Risperidone is a second-generation antipsychotic widely prescribed for a variety of psychiatric disorders. Despite its widespread use, its subacute effects on oxidative metabolism in brain and liver tissues remain poorly understood. This study aimed to evaluate the impact of risperidone on antioxidant enzyme activity and lipid peroxidation in rats. A total of fifteen male Holtzman albino rats were randomly assigned to a Control group (n=5, no risperidone) and two treatment groups (n=5 per group) receiving 0.4 mg kg-1 day-1 and 4.0 mg kg-1 day-1 risperidone, administered via orogastric gavage for 20 consecutive days. After treatment, brain and liver tissues were collected. The activity of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx), Glucose-6-Phosphate Dehydrogenase (G6PDH), and Glutathione S-Transferase (GST) was analyzed. Reduced Glutathione (GSH) levels and lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS), were quantified. Findings indicate that in brain tissue, both doses significantly increased CAT activity and decreased the SOD/CAT ratio, and that the high dose significantly reduced TBARS levels. In liver tissue, a significant increase in CAT activity was observed with the high dose. Furthermore, both doses significantly increased G6PDH activity and reduced TBARS levels. These results underscore the influence of risperidone on cerebral and hepatic oxidative metabolism during the subacute phase.

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