Open AccessAlteration 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
Author(s) -
Rade Vuković,
Dragica Selaković,
Jelena S. Katanić Stanković,
Igor Kumburović,
Nemanja Jovičić,
Gvozden Rosić
Publication year - 2021
Publication title -
journal of integrative neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.336
H-Index - 33
eISSN - 1757-448X
pISSN - 0219-6352
DOI - 10.31083/j.jin2003076
Subject(s) - acetylcysteine , oxidative stress , cisplatin , prefrontal cortex , tail suspension test , lipid peroxidation , neurotoxicity , pharmacology , apoptosis , neuroprotection , chemistry , antioxidant , endocrinology , medicine , toxicity , behavioural despair test , biochemistry , biology , antidepressant , neuroscience , hippocampus , chemotherapy , cognition
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 N-acetylcysteine 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 N-acetylcysteine). The antioxidant supplementation with NAC diminished cisplatin-induced oxidative damage and pro-apoptotic action in the prefrontal cortex, and significantly influenced specific behavioral alterations.