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Volume 9
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10.3390/biom9120892
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Article

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

by
Rade Vukovic
1,
Igor Kumburovic
2,
Jovana Joksimovic Jovic
2,
Nemanja Jovicic
3,
Jelena S. Katanic Stankovic
4,
Vladimir Mihailovic
5,
Milos Djuric
6,
Stefan Velickovic
7,
Aleksandra Arnaut
7,
Dragica Selakovic
2,* and
Gvozden Rosic
2,*
1
Clinic for Anesthesiology and Critical Care, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia
2
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia
3
Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia
4
Department of Science, Institute for Information Technologies Kragujevac, University of Kragujevac, Jovana Cvijica b.b., 34000 Kragujevac, Serbia
5
Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovica 12, 34000 Kragujevac, Serbia
6
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia
7
Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 892; https://doi.org/10.3390/biom9120892
Submission received: 13 November 2019 / Revised: 4 December 2019 / Accepted: 8 December 2019 / Published: 17 December 2019
(This article belongs to the Special Issue Oxidative Damage on Biomolecules and Antioxidants)
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Abstract

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.
Keywords: cisplatin; N-acetylcysteine; oxidative stress; apoptosis; hippocampus; rats cisplatin; N-acetylcysteine; oxidative stress; apoptosis; hippocampus; rats

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MDPI and ACS Style

Vukovic, R.; Kumburovic, I.; Joksimovic Jovic, J.; Jovicic, N.; Katanic Stankovic, J.S.; Mihailovic, V.; Djuric, M.; Velickovic, S.; Arnaut, A.; Selakovic, D.; et al. N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats. Biomolecules 2019, 9, 892. https://doi.org/10.3390/biom9120892

AMA Style

Vukovic R, Kumburovic I, Joksimovic Jovic J, Jovicic N, Katanic Stankovic JS, Mihailovic V, Djuric M, Velickovic S, Arnaut A, Selakovic D, et al. N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats. Biomolecules. 2019; 9(12):892. https://doi.org/10.3390/biom9120892

Chicago/Turabian Style

Vukovic, Rade, Igor Kumburovic, Jovana Joksimovic Jovic, Nemanja Jovicic, Jelena S. Katanic Stankovic, Vladimir Mihailovic, Milos Djuric, Stefan Velickovic, Aleksandra Arnaut, Dragica Selakovic, and et al. 2019. "N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats" Biomolecules 9, no. 12: 892. https://doi.org/10.3390/biom9120892

APA Style

Vukovic, R., Kumburovic, I., Joksimovic Jovic, J., Jovicic, N., Katanic Stankovic, J. S., Mihailovic, V., Djuric, M., Velickovic, S., Arnaut, A., Selakovic, D., & Rosic, G. (2019). N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats. Biomolecules, 9(12), 892. https://doi.org/10.3390/biom9120892

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