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.

Numerous adverse effects of cisplatin-based therapy are usually accompanied by enhanced oxidative damage and cell apoptosis in various tissues. Even neurotoxic manifestations of cisplatin administration, such as the anxiogenic effect, appear along with the increased oxidative stress and apoptotic indicators in certain brain regions. Thirty-five Wistar albino male rats were divided into seven groups: control, cisplatin (received a single dose of cisplatin: 7.5 mg/kg), three groups with oral administration ofSatureja hortensisL. methanolic extract (SH) (low: 50 mg/kg, middle: 100 mg/kg, and high dose: 200 mg/kg) along with cisplatin application, a group with the extract in high dose alone, and a silymarin group (cisplatin and silymarin: 100 mg/kg), in order to evaluate the antioxidant effects of SH on cisplatin-induced increase in the anxiety level. After completing 10-day pretreatments, behavioral testing was performed in the open field and the elevated plus maze, followed by an investigation of oxidative stress and apoptosis parameters in hippocampal tissue samples. Cisplatin administration resulted in anxiogenic-like behavior, increased lipid peroxidation, and proapoptotic markers accompanied by the decline in antioxidant and antiapoptotic defense. The administration of extract alone did not significantly alter any of the estimated parameters. When applied along with cisplatin, SH in a dose of 100 mg/kg induced the significant anxiolytic effect with concomitant recovery of antioxidant and antiapoptotic activity indicators, while both lower and higher doses of the extract failed to improve the adverse effects of cisplatin administration. The beneficial effects of the middle dose of SH were equivalent to the same dose of silymarin, as a “golden standard.” Our results indicate that the antioxidant supplementation with SH in an optimal dose significantly improved the oxidative status and it had antiapoptotic effect in the rat hippocampus disturbed by cisplatin administration, which was accompanied with attenuation of cisplatin-induced anxiogenic effect.

In order to evaluate the effects of Satureja hortensis L. extract on cisplatin-induced behavioral alterations in the tail suspension test (TST), we included 35 male Wistar albino rats in this study, divided into 7 equal groups. Cisplatin was administered (single dose of 7.5 mg/kg, i.p., on the fifth day) alone, and in groups with orally administered (for 10 days) Satureja hortensis L. extract (50, 100, and 200 mg/kg), and silymarin (100 mg/kg) in individual groups. The behavioral testing was performed in TST, and the following parameters were obtained: the latency to the first immobility, the number of immobility episodes, and the total duration of immobility. Cisplatin application increased the latency to the first immobility, but decreased the number of immobility episodes and the total duration of immobility. Oral administration of Satureja hortensis L. extract in a dose of 100 mg/kg attenuated cisplatin-induced alterations, and those effects were similar to silymarin group. The extract in a dose of 200 mg/kg diminished cisplatin-induced effect only for the total duration of immobility, while in a dose of 50 mg/kg, the extract had no impact on cisplatin effects. Although common use of this methodology would lead to a conclusion that cisplatin produced antidepressant effect, comparison with certain literature data allows the conclusion that this action of cisplatin may be attributed to its anxiogenic action that was attenuated by antioxidant supplementation (Satureja hortensis L.) in an adequate dose (100 mg/kg).

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.

The aim of this study was to estimate a potential beneficial influence of N-acetylcysteine (NAC) in the treatment of cisplatin-induced motor impairment. We included 32 male Wistar albino rats, divided into 4 equal groups: control (received saline on the 1st and 5th day), cisplatin – CIS (received saline on the 1st and cisplatin 7.5 mg/kg i.p. on the 5th day), NAC (received NAC on the 1st and 5th day, 500 mg/kg i.p.), and CIS+NAC (received NAC on the 1st and 5th day, 500 mg/kg i.p. and cisplatin 7.5 mg/kg i.p. on the 5th day) group. Motor performance was estimated by rotarod, grip wire, open field (OF), elevated plus maze (EPM) and beam-walking (BW) tests on the 10th day. Cisplatin administration resulted in decreased motor performance in all tests, except for BW test, compared to the control group. NAC supplementation on its own had no significant effect on motor performance parameters. However, simultaneous administration of NAC along with cisplatin reversed negative impact of cisplatin in rotarod, OF and EPM tests, with no significant effect on the results obtained in grip wire test. The results of this study confirmed numerous motoric manifestations of cisplatin-induced neurotoxicity in rats. However, the decline in most of the estimated parameters was successfully prevented by antioxidant supplementation with NAC.