Cimetidine ameliorated the effect of Cisplatin treatment on brain of Wistar rats

Cisplatin (CIS) is an anti-neoplastic drug used for chemotherapy of solid organ malignancies. Unfortunately, it activates processes that induce oxidative damage in the brain (neurotoxicity). Cimetidine (CTD) is a Histamine 2 receptor blocker reported to exhibit antioxidative function. This study investigated the effect of CTD on CIS neurotoxicity in rat. The study was carried out on 40 male Wistar rats randomized into four groups; A, B, C and D, (n=10) and treated as follows: Group-A rats (control) were injected intraperitoneally (IP) with 0.5 mL/kg saline once daily for 14 days, Group-B rats were IP administered 100 mg/kg CTD once daily for 14 days, Group-C rats received 7.5 mg/kg Cisplatin IP on day 7, Group-D rats were IP administered 100 mg/kg CTD for 14 days and CIS (7.5 mg/kg ) on day 7. Behavioural tests were performed on the experimental rats from day 15 to 17 post-treatment after which they were sacrificed under anaesthesia (Ketamine hydrochloride 100 mg/kg). Brain sections were processed into paraffin blocks and H&E stained. Results showed significant weight loss in CIS only group while CTD treatment reduced weight loss significantly (p<0.05) in CTD+CIS group. Behavioural study showed that cimetidine treatment in animals of CTD+CIS group enhanced exploratory ability of the rats in the group, while CIS only group animals exhibited impaired exploratory ability with significantly lower discrimination index. Histological sections of the cerebellum and hippocampus of CIS group of animals showed multiple alterations in their cytoarchitecture, whereas sections from CTD+CIS treated animals appeared normal. In conclusion, these findings suggest that cimetidine exhibited ameliorative effect against cisplatin-induced behavioural deficits and cytoarchitectural distortions of the brain cells of rats.

Key Words: Cisplatin, Cimetidine, Neurotoxicity, Rats