Quercetin 100 mg/kg fails to mitigate cisplatin-induced neurotoxicity in adult Wistar rats

Abstract

OBJECTIVE: The survival rate of cancer patients has improved with cisplatin, a platinum-based chemotherapy. However, neurological deficits are prevalent in cancer patients administered with cisplatin. Interestingly, quercetin is reported to possess neuroprotective and antioxidant properties. We hypothesized that quercetin 100 mg/kg may offer ameliorative potential against cisplatin-induced neurotoxicity.

MATERIALS AND METHODS: Twenty (20) male adult Wistar rats (150 to 180 g) were allotted into four groups (n = 5), namely groups I (placebo distilled water 10 mL kg^-1 body weight), II (cisplatin 5 mg kg^-1 body weight), III (cisplatin/quercetin 5/100 mgkg^-1 body weights,) and IV (quercetin 100 mg kg^-1 body weight, respectively). Cisplatin was administered intraperitoneally, once a week, and twice in 14 days, while quercetin was administered orally once daily for 14 days. Animals were deeply anesthetized with ketamine (100 mg/kg body weight, intraperitoneally). Then transcardially perfused with phosphate buffer saline (PBS) followed by perfusion in 4% paraformaldehyde in PBS (pH 7.4) for fixation. Each brain was harvested and postfixed overnight in the same fixation solution and prepared for tissue processing. Biochemical assays for brain antioxidant level were performed.

RESULTS: No significant change in the levels of antioxidant assays (SOD, CAT, GPx), but we did observe a significant increase in GSH and the levels of MDA (p < 0.005) in all administered groups compared to the control group. Neurodegenerations with pyknotic neurons and vacuolations were demonstrated in administered groups of the cerebellum, prefrontal cortex and hippocampus, with neuronal cell shrinkages and hyperchromatic cells

CONCLUSION: The results suggest that 100 mg/kg bw of quercetin cannot not ameliorate cisplatin-induced neurotoxicity in rats thus more of quercetin may not always be better. It is necessary to determine the dose beneficial threshold of quercetin.