CYTOREMEDIATIVE POTENTIALS OF Vitellaria paradoxa (Gaertn. C.F) IN ARSENIC-INDUCED TOXICITY IN WISTAR RAT, HARWICH FRUIT FLY AND ITS ANTIPROLIFERATIVE ACTIVITY IN MCF-7 CELLS

Abstract

Arsenic, a class 1 carcinogen, is a major contaminant in drinking water globally. When ingested by humans and animals, it contributes to tissue damage through the mechanisms of oxidative stress and inflammation. Search is ongoing for plants with antioxidative and anti-inflammatory properties that might ameliorate toxic effects of arsenic. Vitellaria paradoxa (Vp) was reported to possess anti-oxidative and anti-inflammatory properties. Therefore, cytoremediative potentials of Vp against Sodium arsenite (SA)-induced toxicity in Wistar rats and fruit fly (Drosophila melanogaster), as well as its anti-proliferative action on breast cancer cell line (MCF-7) were evaluated. Leaves of Vp were obtained from Saki, Oyo State, authenticated at University of Ibadan Herbarium (UIH-22624), air-dried and pulverised. Hydroethanol leaf extract of Vp was obtained by maceration in 70% ethanol (ELVp), and fractionated by vacuum liquid chromatography to obtain four fractions including Ethyl acetate Fraction (EAcF). Forty male Wistar rats, divided into 8 groups (n=5), were administered distilled water 2mL/kg (Control), Vitamin E (100 mg/kg), ELVp (100, 200 mg/kg), SA (2.5 mg/kg), SA + Vitamin E, SA + ELVp (100, 200 mg/kg) orally for 14 days. Serum Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), creatinine, urea and malondialdehyde were determined spectrophotometrically. Micronucleated Polychromatic Erythrocytes (mPCE), liver and kidney histology and immunohistochemistry of proteins [(Nuclear Factor kappa B (NF-κB), P53, B-Cell Lymphoma 2 (BCL-2)] were evaluated. Ameliorative role of EAcF in SA-induced toxicity in D. melanogaster was evaluated by measuring longevity rate, Nitric Oxide (NO), Hydrogen Peroxide (H2O2), Total Thiol (T-SH), reduced glutathione (GSH) levels, catalase and glutathione S-transferase (GST) activities. Anti-proliferative effects of EAcF on MCF-7 cells were determined by measuring viability, colony formation and Reactive Oxygen Species (ROS) generation. Also, cell cycle was determined using flow cytometer. Data were analysed using ANOVA at α0.05. Co-treatment of SA with ELVp (100 mg/kg) significantly reduced serum ALT (68.73±0.50 vs 89.67±8.78U/L), ALP (174.80±1.84 vs 450.20±69.47U/L), creatinine (1.32±0.00 vs 1.93±0.15mg/dL), urea (33.72±9.07 vs 75.14±1.13mg/dL), malondialdehyde (0.049±0.005 viii vs 0.067±0.012µmol/gprotein) and mPCEs (10.00±2.83 vs 16.00±2.00mPES/1000PCEs) relative to SA. The ELVp (200 mg/kg) ameliorated SA-induced severe periportal and mild peritubular inflammation of the liver and kidney of rats, respectively. The ELVp ameliorated SA-induced increase in BCL-2 protein expression without significant effects on NF-κB and P53 expression in both organs. The EAcF increased longevity of D. melanogaster by 20.0% compared with control and ameliorated SA-induced elevation of NO and H2O2 levels by 24.0% and 19.0%, respectively. Also, it ameliorated SA-induced reduction of contents of T-SH by 88.0%, GSH by 253.0% and inhibition of catalase and GST activities by 57.8% and 156.0% respectively. The EAcf showed anti-proliferative activity, reduced ROS generation, induced Sub G0 cell death and arrest at G0/G1 phase in MCF-7 cells. Hydroethanol leaf extract and ethyl acetate fraction of Vitellaria paradoxa demonstrated antihepatotoxic, antinephrotoxic and antioxidative properties against sodium arsenite induced toxicity in rat and Drosophila melanogaster. The anti-proliferative activity in MCF 7 cells was via inhibition of reactive oxygen species accumulation and G0/G1 cell cycle arrest.