Neuroprotective mechanisms and ameliorative activities of quercetin in cisplatin-induced cerebellum neurotoxicity in rat models

• Quercetin (QC) is a naturally occurring phytochemical with promising bioactive effects. • Cisplatin (CP) is a highly effective antitumor agent, but its clinical use is limited due to critical adverse reactions including neurotoxicity. • Quercetin restored brain metabolic enzyme activities, increased neurotransmitters, and prevented neuromorphological alterations. • Quercetin protects rats’ brains against CP-induced cerebellum neurotoxicity. Cisplatin (CP) is a highly effective antitumor agent, but its clinical use is limited due to critical adverse reactions including neurotoxicity. Quercetin (QC) is a naturally occurring phytochemical with promising bioactive effects. This study investigated the Neuroprotective mechanisms and ameliorative activities of quercetin in cisplatin-induced cerebellum neurotoxicity in rat models. The rats were randomly divided into five groups of six ( n = 6) rats. Group A, served as control. Group B, received a single dose of 10 mg/kg body weight (bwt) of CP (i.p.) on the first day. Group C received 30 mg/kg bwt of QC. Group D received a single dose of 10 mg/kg bwt CP on the first day followed by 30 mg/kg bwt of QC. Group E received 30 mg/kg bwt of QC per day followed by a single dose of 10 mg/kg bwt of CP on the last day. The treatment lasted for 35 days after which the novel-object recognition memory test (NORT) was used to assess non-spatial memory function. Brain neurochemical status was assessed and brain tissues were processed for histology. Quercetin increased weight loss and cognitive performance in CP-treated rats by enhancing the exploration of unfamiliar objects. Quercetin protects the brain from CP-mediated alterations in oxidative status, as well as brain metabolic enzyme indicators. It also decreased IL-6, IL-1, and TNF-α, and NF-ĸB expression, restored brain metabolic enzyme activities, increased neurotransmitters, and prevented neuromorphological alterations. In conclusion, quercetin protects rats’ brains against CP-induced cerebellum neurotoxicity via oxidative stress inhibition and down-regulation of inflammation.