Lead-induced oxidative stress in postnatal developing cerebellum of Wistar rats: role of aqueous extract of Cucumis sativus Linn and vitamin C

Abstract

Lead (Pb) is one of the most abundant heavy metal whose toxicity causes environmental and health problems, with the brain being highly sensitive to lead toxicity. There is limited literature regarding the protection of the developing brain against lead-induced toxicity. However, plant-derived products with antioxidant activity have been useful in reducing lead-induced neurotoxicity. This study investigated the role of Cucumis sativus (C. sativus) (Cucumber) and vitamin C in lead-induced oxidative stress in postnatal developing cerebellum of Wistar rats. Twenty-five pregnant Wistar rats weighing between 160 and 180g were divided into five groups (n=5). Group I served as control and received water, group II received 50mg/kg of lead acetate, group III received 200mg/kg aqueous extract of C. sativus, group IV received 200mg/kg of C. sativus and 50mg/kg of lead acetate and group V received 200mg/kg of vitamin C and 50mg/kg of lead acetate. The interventions were administered orally using an oral gavage from the first day of gestation to postnatal day 21. Neurobehavioural assessment (forelimb grip strength and negative geotaxis) was carried out on pups of day 21 and then sacrificed. Some cerebella of pups of days 1, 7, 14, 21 and 28 were fixed in 10% formol-saline for histological and immunohistochemical evaluations, while others (day 21) were preserved in in phosphate buffered saline at 4°C and pH 7.2 for oxidative stress assays. Data were analysed using ANOVA at p<0.05. Decreased body weight of Pb-treated pups on days 14 and 21, decreased forelimb grip and increased negative geotaxis, increased lipid peroxidation (LPO), decreased glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities was seen in the lead-treated day 21 pups compared with the control and other treated groups. Histologically, in the cerebellar cortex, there was persistent external granular layer (EGL) on day 21 in the treated groups compared with the control, decreased molecular layer (ML) thickness and depleted Pc in the Pb-treated day 28 pups, and increased astrocyte population on day 21 pups compared with the control and C. sativus groups. Lead induced oxidative stress which caused behavioural deficit and morphological changes in the postnatal developing cerebellum of rats. Aqueous extracts of Cucumis sativus and vitamin C decreased the rate at which lead induced neurotoxicity.