Cargando…

N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats

Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of N-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar...

Descripción completa

Detalles Bibliográficos
Autores principales: Vukovic, Rade, Kumburovic, Igor, Joksimovic Jovic, Jovana, Jovicic, Nemanja, Katanic Stankovic, Jelena S., Mihailovic, Vladimir, Djuric, Milos, Velickovic, Stefan, Arnaut, Aleksandra, Selakovic, Dragica, Rosic, Gvozden
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995611/
https://www.ncbi.nlm.nih.gov/pubmed/31861240
http://dx.doi.org/10.3390/biom9120892
_version_ 1783493408707313664
author Vukovic, Rade
Kumburovic, Igor
Joksimovic Jovic, Jovana
Jovicic, Nemanja
Katanic Stankovic, Jelena S.
Mihailovic, Vladimir
Djuric, Milos
Velickovic, Stefan
Arnaut, Aleksandra
Selakovic, Dragica
Rosic, Gvozden
author_facet Vukovic, Rade
Kumburovic, Igor
Joksimovic Jovic, Jovana
Jovicic, Nemanja
Katanic Stankovic, Jelena S.
Mihailovic, Vladimir
Djuric, Milos
Velickovic, Stefan
Arnaut, Aleksandra
Selakovic, Dragica
Rosic, Gvozden
author_sort Vukovic, Rade
collection PubMed
description Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of N-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar albino rats divided into four groups (control, cisplatin, NAC, and CIS + NAC). All treatments were delivered intraperitoneally. On day one, the control and cisplatin groups received saline while the NAC and CIS + NAC groups were administered with NAC (500 mg/kg). On the fifth day, the control group received saline while the CIS group was treated with cisplatin (7.5 mg/kg), the NAC group again received NAC (500 mg/kg), and the CIS + NAC group was simultaneously treated with cisplatin and NAC (7.5 and 500 mg/kg, respectively). Behavioral testing, performed on the tenth day in the open field (OF) and elevated plus maze (EPM) tests, revealed the anxiogenic effect of cisplatin that was significantly attenuated by NAC. The hippocampal sections evaluation showed increased oxidative stress (increased lipid peroxidation and decline in antioxidant enzymes activity) and proapoptotic action (predominantly by diminished antiapoptotic gene expression) following a single dose of cisplatin. NAC supplementation along with cisplatin administration reversed the prooxidative and proapoptotic effects of cisplatin. In conclusion, the results obtained in this study confirmed that antioxidant supplementation with NAC may attenuate the cisplatin-induced anxiety. The mechanism of anxiolytic effect achieved by NAC may include the decline in oxidative damage that down regulates increased apoptosis and reverses the anxiogenic action of cisplatin.
format Online
Article
Text
id pubmed-6995611
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-69956112020-02-13 N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats Vukovic, Rade Kumburovic, Igor Joksimovic Jovic, Jovana Jovicic, Nemanja Katanic Stankovic, Jelena S. Mihailovic, Vladimir Djuric, Milos Velickovic, Stefan Arnaut, Aleksandra Selakovic, Dragica Rosic, Gvozden Biomolecules Article Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of N-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar albino rats divided into four groups (control, cisplatin, NAC, and CIS + NAC). All treatments were delivered intraperitoneally. On day one, the control and cisplatin groups received saline while the NAC and CIS + NAC groups were administered with NAC (500 mg/kg). On the fifth day, the control group received saline while the CIS group was treated with cisplatin (7.5 mg/kg), the NAC group again received NAC (500 mg/kg), and the CIS + NAC group was simultaneously treated with cisplatin and NAC (7.5 and 500 mg/kg, respectively). Behavioral testing, performed on the tenth day in the open field (OF) and elevated plus maze (EPM) tests, revealed the anxiogenic effect of cisplatin that was significantly attenuated by NAC. The hippocampal sections evaluation showed increased oxidative stress (increased lipid peroxidation and decline in antioxidant enzymes activity) and proapoptotic action (predominantly by diminished antiapoptotic gene expression) following a single dose of cisplatin. NAC supplementation along with cisplatin administration reversed the prooxidative and proapoptotic effects of cisplatin. In conclusion, the results obtained in this study confirmed that antioxidant supplementation with NAC may attenuate the cisplatin-induced anxiety. The mechanism of anxiolytic effect achieved by NAC may include the decline in oxidative damage that down regulates increased apoptosis and reverses the anxiogenic action of cisplatin. MDPI 2019-12-17 /pmc/articles/PMC6995611/ /pubmed/31861240 http://dx.doi.org/10.3390/biom9120892 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vukovic, Rade
Kumburovic, Igor
Joksimovic Jovic, Jovana
Jovicic, Nemanja
Katanic Stankovic, Jelena S.
Mihailovic, Vladimir
Djuric, Milos
Velickovic, Stefan
Arnaut, Aleksandra
Selakovic, Dragica
Rosic, Gvozden
N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats
title N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats
title_full N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats
title_fullStr N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats
title_full_unstemmed N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats
title_short N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats
title_sort n-acetylcysteine protects against the anxiogenic response to cisplatin in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995611/
https://www.ncbi.nlm.nih.gov/pubmed/31861240
http://dx.doi.org/10.3390/biom9120892
work_keys_str_mv AT vukovicrade nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT kumburovicigor nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT joksimovicjovicjovana nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT jovicicnemanja nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT katanicstankovicjelenas nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT mihailovicvladimir nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT djuricmilos nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT velickovicstefan nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT arnautaleksandra nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT selakovicdragica nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats
AT rosicgvozden nacetylcysteineprotectsagainsttheanxiogenicresponsetocisplatininrats