Phenytoin-induced toxicity in the postnatal cerebellar development in rat: effect of calotropis procera on selective biochemical and haematological variables

Phenytoin, an antiepileptic drug is used in managing seizures. Phenytoin-associated oxidative stress causes cellular damage by the generation of free radicals. Vitamin C, a standard antioxidant and Calotropisprocera are believed to scavenge oxygen free radicals. The effect of C. procera extract on haematological and biochemical variables in an in-vivo model was studied. Pregnant rats were administered phenytoin (50 mg/kgbody weight). Extracts of C. procera (300 mg/kg body weight) and vitamin C (200 mg/kg body weight) were administered one hour prior to phenytoin treatment separately, while control animals received tap water only.The animals had access to food and water ad libitum. Blood was collected from animals on day 50 postpartum for packed cell volume (PCV), haemoglobin (Hb) content and evaluation of levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) evaluation. Lipid peroxidase (LPO) and reduced glutathione (GSH) levels in the cerebellum were assessed as markers of oxidative stress on day 50 postpartum. Phenytoininduced toxicity was associated with increased cerebellar LPO and decreased GSH levels. Increase in ALT andAST levels in the serum was observed. However, PCV and Hb levels were not affected. LPO, GSH, ALT and AST levels registered a tendency to shift towards normalcy on administration of C. procera and vitamin C tophenytoin. In conclusion, supplementation with C. procera leaf extract reduced the rate at which phenytoin induced toxicity in developing rat cerebellum postnatally

Protective role of Telfairia occidentalis in irradiation-induced oxidative stress in rat brain

This study aimed at evaluating the protective role of Telfairia occidentalis extract (TOE) irradiationinduced oxidative stress in rat brain. Aqueous TOE was administered orally to adult rats for 30 days at doses of 400 mg/kg body weight, 800 mg/kg body weight and 1600 mg/kg body weight, and a corresponding group of rats were treated with 50 mg/kg body weight vitamin E (VE), a standard antioxidant before irradiation at a dose of 2 Gy of gamma rays. The control rats received distilled water only. The rats were observed and sacrificed at 24 hours, 15 and 30 days post-irradiation. The results demonstrated a significant increase in levels of malondialdehyde (MDA), an end product of lipid peroxidation (LPO) and hydrogen peroxide (H2O2) generation with a concomitant decrease in the activities of  superoxide dismutase (SOD), glutathione peroxidase (GSH-Px),  glutathione-S-transferase (GST), a phase two xenobiotic metabolizing enzyme, and a corresponding decrease in the level of reduced glutathione (GSH) after twenty-four hours, 15 and 30 days post-irradiation compared with the control. Treatments with TOE and VE significantly reversed  oxidative stress of irradiated rats when compared with the control rats. In conclusion, supplementation with TOE could reduce radiationinduced biochemical disorders in brain tissues.Keywords: Gamma radiation, oxidative stress, brain, rats and Telfairia occidentalis

Kola nut from Cola nitida vent. Schott administered to pregnant rats induces histological alterations in pups’ cerebellum

Kola nut (from Cola nitida) is popular in Nigeria and West Africa and is commonly consumed by pregnant women during the first trimester to alleviate morning sickness and dizziness. There is, however, a dearth of information on its effects on the developing brain. This study, therefore, investigated the potential effects of kola nut on the structure of the developing neonatal and juvenile cerebellum in the rat. Pregnant Wistar rats were administered water (as control) or crude (aqueous) kola nut extract at 400, 600, and 800 mg/kg body weight orally, from pregnancy to day 21 after birth. On postnatal days 1, 7, 14, 21 and 28, the pups were weighed, anaesthetised, sacrificed and perfused with neutral buffered formalin. Their brains were dissected out, weighed and the cerebellum preserved in 10% buffered formalin. Paraffin sections of the cerebellum were stained with haematoxylin and eosin for cerebellar cytoarchitecture, cresyl violet stain for Purkinje cell count, Glial Fibrillary Acidic Protein (GFAP) immunohistochemistry (IHC) for estimation of gliosis, and B-cell lymphoma 2 (Bcl-2) IHC for apoptosis induction. The kola nut-treated rats exhibited initial reduction in body and brain weights, persistent external granular layer, increased molecular layer thickness, and loss of Bergmann glia. Their Purkinje cells showed reduction in density, loss of dendrites and multiple layering, and their white matter showed neurodegeneration (spongiosis) and GFAP and Bcl-2 over-expression, with evidence of reactive astrogliosis. This study, therefore, demonstrates that kola nut, administered repeatedly at certain doses to pregnant dams, could disrupt normal postnatal cerebellar development in their pups. The findings suggest potential deleterious effects of excessive kola nut consumption on human brain and thus warrant further studies to understand the wider implications for human brain development