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

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.

The Beneficial Role of Filipendula ulmaria Extract in Prevention of Prodepressant Effect and Cognitive Impairment Induced by Nanoparticles of Calcium Phosphates in Rats

“…Prefrontal cortex (PFC) homogenates were prepared according to the standard procedure previously established in our lab, as reported by Kumburovic and coworkers [ 32 ] and Vukovic and colleagues [ 33 ], with the chemicals listed in Supplementary file 2 . Principally, phosphate-buffered saline (PBS, pH 7.4) was used for PFC tissue homogenization, and after centrifugation at 4000 rpm for 15 min at 4°C, the supernatant was separated and used for further analyses.…”

Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review

“…N-Acetylcysteine (NAC) is a precursor of glutathione which can increase the concentration of glutathione in blood and thus increase the antioxidative defense in the organism [ 99 ]. The effects of NAC were studied in cisplatin-treated rats showing reduced levels of oxidative stress parameters in rodents as well as significant anxiolytic properties [ 83 ]. NAC was also potent in regulating cognitive performance and improving the histomorphological parameters that were disrupted by cisplatin administration [ 74 ].…”

N‐acetylcysteine as a new prominent approach for treating psychiatric disorders

“…and anti-apoptotic effects (increase in anti-apoptotic gene expression) in the rat hippocampus (Vukovic et al, 2019). Notably, the administration of NAC to control animals did not alter behavioural and molecular analyses (Vukovic et al, 2019 (Famitafreshi & Karimian, 2020). A single dose of NAC (15, 30, or 120 mg kg À1 ; i.p.)…”

“…Similarly, the increased anxiogenic effect of cisplatin was reversed by NAC (500 mg kg −1 ; 5 days before and simultaneously with cisplatin application; i.p.) administration, as shown by the anti‐oxidant (increases in SOD and CAT activities and a reduction in TBARS levels) and anti‐apoptotic effects (increase in anti‐apoptotic gene expression) in the rat hippocampus (Vukovic et al, 2019). Notably, the administration of NAC to control animals did not alter behavioural and molecular analyses (Vukovic et al, 2019).…”