ANTICONVULSANT AND SUB-CHRONIC TOXICITY STUDIES OF THE METHANOL LEAF EXTRACT OF DIOSPYROS MESPILIFORMIS HOCHST (EBENACEAE) IN LABORATORY ANIMALS

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ANTICONVULSANT AND SUB-CHRONIC TOXICITY STUDIES OF THE METHANOL LEAF EXTRACT OF DIOSPYROS MESPILIFORMIS HOCHST (EBENACEAE) IN LABORATORY ANIMALS

Abstract:

Diospyros mespiliformis hochst (Ebenaceae) known in English as ebony is a plant that is found throughout West Africa. The Plant was reported to have wide ethnomedical application notably in fever, whooping cough, wounds, pneumonia, syphilis, leprosy and epilepsy among others. This study examined the anticonvulsant activity of its methanol leaf extract in mice and day old chicks against pentylenetetrazole, maximal electroshock, strychnine and 4 amino pyridine induced seizure tests. Valproic acid, phenytoin and phenobarbitone respectively were used as reference anticonvulsant drugs for comparison. The sub-chronic toxicity studies was also carried out in rats to determine the effect of twenty eight days p.o.(per oral) administration of the methanol leaf extract of D.mespiliformis on renal and hepatic function parameters followed by histopathological examination. The extract at i.p.(intraperitoneal) doses of 50, 100 and 200mg/kg protected the mice (50%, 66.67% and 66.67%) against pentylenetetrazole induced seizures respectively the mean onset of seizure was however not significantly increased when compared with the negative control at P<0.05. The extract at i.p doses of 250, 500 and 1000 mg/kg did not produced any significant anticonvulsant activity against maximal electroshock induced seizure, similarly, at i.p doses of 50, 100 and 200 mg/kg, the extract also did not show any significant activity against 4-amino pyridine induced seizure even though it showed only 16.67% protection with the 200mg/kg dose. Also no significant activity against strychnine induced seizure even though it significantly (P<0.05) prolonged the onset of seizure induced by strychnine but failed to protect the animals against strychnine induced lethality. The methanol leaf extract of D.mespiliformis causes significant elevation of alkaline phosphatase (ALP) at p.o. doses of 50 mg/kg (P<0.05), 500mg/kg (P<0.05) and 1000 mg/kg (P<0.001), the values of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST), Total bilirubin were however not significantly elevated at p.o doses of 50, 250, 500 and 1000 mg/kg. In the renal function tests, the result showed significantly elevated potassium levels at p.o dose of 250 mg/kg P<0.05 and also significant decrease in creatinine values at p.o. doses of 250, 500 and 1000 mg/kg at P<0.01 respectively. No significant changes in the values of sodium, total calcium, glucose, total cholesterol, urea, total protein and albumin at P<0.05. Histopathological studies on the other hand revealed moderate (with 500 mg/kg p.o dose) to severe (with 1000 mg/kg p.o. dose) degeneration of hepatocytes, hepatocellular necrosis and lose of hepatic architecture with the liver and moderate (with 500 mg/kg p.o. dose) to severe (with 1000 mg/kg p.o dose) loss of renal tubular architecture and degeneration of renal tubules but with intact glomerali with the kidney. The median lethal dose (LD50) values of D.mespiliformis methanol leaf extract were found to be 774.6mg/kg i.p. and >5000 mg/kg p.o. in both rats and mice. While in chicks, the value was found to be >5000 mg/kg intraperitoneally. The preliminary phytochemical screening revealed the presence of alkaloids, saponins, flavonoids, tannins, carbohydrates, cardiac glycosides, and combined anthracene type of anthraquinones. These results suggests that D.mespiliformis leaf extract posses biologically active phytoconstituents that have anticonvulsant activity and are hepatotoxic and nephrotoxic at higher doses

ANTICONVULSANT AND SUB-CHRONIC TOXICITY STUDIES OF THE METHANOL LEAF EXTRACT OF DIOSPYROS MESPILIFORMIS HOCHST (EBENACEAE) IN LABORATORY ANIMALS

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