Toxic Effect Study of Methanol Extract of Terminalia Glaucesens Leaves Following Single or Short-Term Repetitive Oral Administration in Swiss Mice

Abstract

The uses of different parts of the plant Terminalia glaucescens in traditional medicine is well known in some African countries. Thus, the methanol or aqueous extract of plant leaves or roots was pharmacologically studied for its benefit effects in malaria, diabetes, cardiac and hepatic diseases. However, there is no investigation in probable adverse effect in order to determine safety dose for human users. In consequence, the aim of the present study was to evaluate both acute and sub-acute toxicity of methanol extract of Terminalia glaucescens leaves in Swiss mice following single oral and repetitive administration. As results, the oral LD50 of the preparation in Swiss mice was found to be greater than 2500 mg/kg body weight (bw). In the repetitive toxicity study, Swiss mice (10/sex/group) were administered via oral gavage 0 (control), 13.90 (traditional therapeutic dose for malaria) and high dose 1390 mg/kg bw/day of the plant leaves extract for 15 days. Administration of the plant leaves preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations. Interestingly, benefit effects have been observed in body weights for therapeutic dose (13.90 mg/kg bw/day) and some organs weight such as kidney and spleen (for females) were increased. Hepatoprotection and hypolipidemic actions have been observed with serum ALT and lipids (total cholesterol and triglycerides) decrease in mice having received therapeutic dose (13.90 mg/kg bw/day). In addition, benefit effect has been observed in hemoglobin amount in animal treated by therapeutic dose. In parallel, precocious adverse effects have been observed with high dose of 1390 mg/kg bw/day in body weights and hemoglobin amounts and leukocytes cells number which were decreased when compared to control (p<0.01). This leucopenia was not linked to lymphocytes because they stayed unchanged. Probable neutropenia or myelotoxic effect could be the etiology of such leucopenia. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for methanol extract of Terminalia glaucescens leaves in Swiss mice could be near but under 1390mg/kg bw/ day.