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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/4615

Title: Safety Evaluation of a Polyherbal Antihypertensive Mixture Used in Ghana in Mice
Authors: Koffuor, George Asumeng
Issue Date: 28-Jun-2012
Abstract: Herbal medicine in being used extensively globally with the notion that they are natural and therefore relatively safe compared to other forms of medicine. This study therefore assessed the safety of an FDB approved polyherbal anti-hypertensive used extensively in Ghana. Using ICR mice, the effect of 32 - 550 mg/kg/day of the product on; general health, locomotory activity, muscular coordination and strength, vestibular function, organ functions, hematological, lipid, and histopathological profiles, urine content, pentobarbitone-induced sleeping time, cytochrome P450 activity and reproductive toxicity was assessed. One hour post-treatment observation in acute toxicity studies showed sedation and lethargy and a significant dose-dependent reduction (P ≤ 0.05-0.001) in locomotion, rearing, centering, grip strength, muscle coordination, and righting response. These observations were however not significant 24 h post-treatment. Acute toxicity studies also showed no significant differences in hematological profile (except in WBC), liver function, kidney function (in plasma urea), and urine content up to 10 days post-treatment. A 45-day sub-chronic toxicity study showed no physical deterioration, and observable clinical and autonomic toxic symptoms. Among other vital organs, only the liver showed significant decrease (P ≤ 0.01-0.001) in organ weight to body weight ratio with treatment. WBC increased significantly (P ≤ 0.05 – 0.001) while RBC, MCV, and RBC distribution width were not affected. HGB decreased significantly (P ≤ 0.001) after 23 days but normalized. HCT, PCT and PDW increased significantly (P ≤ 0.001) and MCH and MCHC were significantly reduced (P ≤ 0.01-0.001). Plasma albumin decreased (P ≤ 0.01 – 0.001) initially but later increased significantly (P ≤ 0.001) globulin levels increased significantly (P ≤ 0.001) hence a significant increase (P ≤ 0.001) in total protein. ALT, AST, ALP increased significantly (P ≤ 0.01) after 23 days post-treatment but decreased very significantly (P ≤ 0.001) below the control after 45 days. Direct, indirect, and total bilirubin increased significantly (P ≤ 0.001) with duration of treatment. Plasma urea decreased significantly (P ≤ 0.001) but creatinine increased significantly (P ≤ 0.001) with higher dosing and longer treatment time. Total cholesterol and HDL reduced very significantly (P ≤ 0.001) initially but returned to normal while TAG, VLDL, and LDL were significantly very high (P ≤ 0.001) initially but reduced by day 45. Urine analysis showed no significant changes. The liver, kidney and spleen showed histopathological changes. Pentobarbitone-induced sleeping time was prolonged. Liver cytochrome P450 level decreased very significantly (P ≤ 0.001). Observations made suggested that the product is not lethal but had CNS depressant, anxiolytic, and probably muscle relaxant activity which affected activity and neurological behavior. It did not have abnormal proliferative effect on blood forming cells but caused microcytic-anisocytic anaemia. Liver synthetic and excretory functions colud be affected with its use. Concomitant administration with other drugs could result in some drug interaction as the product inhibits CYP 450. Within limits of the doses administered in this study, it did not cause reproductive toxicity.
Description: A Thesis submitted to the School of Graduate Studies, Kwame Nkrumah University of Science and Technology, Kumasi, in partial fulfilment of the requirements for the Degree of Doctor of Philosophy, June-2012
URI: http://hdl.handle.net/123456789/4615
Appears in Collections:College of Health Sciences

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