Biflavonoid quercetin protects against cyclophosphamide-induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity.

Abstract

Cyclophosphamide use has been associated with increased oxidative stress in cells and tissues. Quercetin's antioxidative properties make it of potential benefit in such conditions of oxidative stress. To assess quercetin's ability to mitigate cyclophosphamide-induced organ toxicities in rats. Sixty rats were assigned into six groups. Groups A and D served as normal and cyclophosphamide control and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin at 200 mg/kg of feed. Groups A-C received intraperitoneal (ip) normal saline on days 1 and 2, while D-F received ip cyclophosphamide (150 mg/kg/day on days 1 and 2). On day 21, behavioural tests were carried out, animals were sacrificed and blood samples taken. Organs were processed for histological study. Quercetin reversed cyclophosphamide-induced decrease in body weight, food intake and total antioxidant capacity, and increase in lipid peroxidation (p = 0.001), It also reversed derangement in levels of liver transaminase, urea, creatinine and proinflammatory cytokines (p = 0.001). Improvement in working-memory and anxiety-related behaviours were also observed. Finally, quercetin reversed alterations in levels of acetylcholine, dopamine and brain-derived neurotropic factor (p = 0.021); while reducing serotonin levels and astrocyte immunoreactivity. Quercetin shows significant ability to protect against cyclophosphamide-induced changes in rats.