Bagbasi  Mah

OBJECTIVES /BACKGROUND:
This study aims to investigate the effect of edaravone in preventing cisplatin-induced brain damage.

MATERIAL and METHOD:
Forty female Wistar albino rats were included in the study. 4 groups were created. In group 1 (control group) (n=10), neither any drugs were given nor anything was performed. Group 2 (cisplatin group) (n=10), single dose 7.5 mg/kg cisplatin was given. In group 3 (edaravone group) (n=10), single dose 1 mg/kg edaravone was administered. Group 4 (cisplatin+ edaravone group) (n=10), single dose 7.5 mg/kg cisplatin and 1 mg/kg edaravone were given. Brain tissue was removed in all rats after 3 days. Blood samples taken from heart tissue were examined for malondialdehyde (MDA) and nitric oxide (NO) levels. Brain tissue was evaluated for damage with p53, GFAP and Ki 67.

RESULT:
Edaravone reduced cisplatin-induced brain damage. MDA and NO levels in the cisplatin group were significantly higher than the other groups (p< 0.05). Likewise, tissue damage in the cisplatin group was significantly higher than in the other groups (p< 0.05). The immunohistochemical staining which was done by using p53, GFAP and Ki 67 was shown that tissue damage was higher in cisplatin group than cisplatin+ edaravone group and this difference was found to be statistically significant (p< 0.05).

DISCUSSION:
In this experimental study, the effect of edaravone on brain injury due to cisplatin was investigated. MDA levels appear to be increased and NO levels appear to be decreased according to our study. The tissue damage scores such as vascular changes, edema, and inflammation were more intense in the cisplatin group than cisplatin+edaravone group. Immunostaining with GFAP gave the same histological findings as light microscopy. Addition of edaravone reversed cisplatin-related adverse effects. The platinum inside cisplatin combines with DNA of the cell. The amount of this platinum-DNA complex increases with the dose and duration of administration of cisplatin. As a result, intracellular toxicity occurs. In addition, oxidative stress caused by cisplatin leads to an increase in free radical and ROS levels in the cell (Borovskaya et al. 2004). p53 gene expression is increased as a result of DNA damage. All these protective mechanisms are geared towards repairing DNA damage (Dixit et al. 1997). Resveratrol is an antioxidant that is found in many plants and has an antioxidant effect due to the phenol extract of it. Due to its antioxidant effect, resveratrol reduces free radicals formed as a result of oxidative stres (Kara et al. 2022). Subsequently, effects of vitamin C, vitamin E have been demonstrated against the testicular injury in the rats administered valproic acid (Ourique et al. 2016). Abe et al reported that edaravone reversed the harmful effects due to liver ischemia (2004). Later, Kara et al reported that edaravone could be an effective agent in the short-term treatment and prevention of ovarian ischemia and reperfusion damage (2012). Kawasaki et al reported that edaravone might have a neuroprotective effect by reducing levels of OH- metabolites, increasing NO production and decreasing nNOS expression in brain cells (Kawasaki et al. 2020).Theories about the mechanism of action of edaravone are relation with neutralizing free radicals, scavenging ROS, inhibiting lipid peroxidation, and detoxifying hydroxyl radicals (Tamamura et al. 2009). For the reasons listed, it was thought that edaravone may be useful in the prevention of cisplatin-induced brain damage. In this study, serum MDA levels were found to be significantly higher in the cisplatin group than the cisplatin+edaravone group (p<0.05). On the contrary, NO levels were significantly lower in the cisplatin group than the cisplatin+edaravone group (p<0.05). It was also observed that edaravone diminished the histopsthologic damage. Cerebral injury criteria such as vascular changes, edema, and inflammation were evaluated. Edaravone improved the morphology and microscopic appearance of the cerebral tissue. The improvement in the morphology and structural characteristics was prominent in the cisplatin+edaravone group. Limitations of our study are the difficulty in adapting the findings in rats to humans and the relatively small sample size. In conclusion, edaravone, a novel free-radical scavenger, was evaluated as a protective chemical on cisplatin induced cerebral injury. According to our short- term findings, edaravone seems to reverse cerebral injury due to cisplatin. However, large prospective, randomized trials are required.