Alteration of Oxidative stress and apoptotic markers alterations in the rat prefrontal cortex influence behavioral response induced by cisplatin and N-acetylcysteine in the tail suspension test

Cisplatin therapy is often accompanied by neurotoxicity manifestation, and since the prefrontal cortex is strongly involved in emotion regulation, the aim of this study was to analyze the alterations in the oxidative and apoptotic status of this brain region, with its behavioral impact in rats, following cisplatin administration, with or without N-acetylcysteine supplementation. Thirty-two male Wistar albino rats were randomly divided into four equal experimental groups: control, cisplatin group (single dose of 7.5 mg/kg, intraperitoneally (i.p.), on the fifth day), N-acetylcysteine group (500 mg/kg i.p., on the first and the fifth day), cisplatin + N-acetylcysteine group. Behavioral testing was performed in the tail suspension test. Oxidative stress and apoptotic markers were determined in the prefrontal cortex tissue samples. Cisplatin administration increased lipid peroxidation and decreased the activity of antioxidant enzymes in the prefrontal cortex. Also, cisplatin induced increase in Bax and decrease in Bcl-2 relative gene expression. Simultaneous application of Nacetylcysteine diminished cisplatin-induced alterations in oxidative stress and apoptotic markers. The results obtained in the tail suspension test that nominally resembles antidepressant action of cisplatin (attenuated by N-acetylcysteine), should be attributed to strong motor expression of anxiogenic response to cisplatin (also reversed by Nacetylcysteine). The antioxidant supplementation with NAC diminished cisplatin-induced oxidative damage and pro-apoptotic action in the prefrontal cortex, and significantly influenced specific behavioral alterations.

Automated summary

This study aimed to analyze the alterations in the oxidative and apoptotic status of the prefrontal cortex in rats following cisplatin administration, and its behavioral impact. The results showed that N-acetylcysteine supplementation could mitigate the neurotoxic effects of cisplatin. The study highlights the importance of the antioxidant NAC in alleviating cisplatin-induced oxidative damage and pro-apoptotic action.