TOXICITY AND IMMUNOMODULATORY PROPERTIES OF METHANOL EXTRACT OF THE STEM BARK OF LANNEA ACIDA A. RICH. (ANACARDIACEAE) IN WISTAR RATS
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ABSTRACT
Lannea acidaA. Rich.belongs to the family of Anacardiaceae; and the bark, leaves and roots have been reported to possess many medicinal properties, including immunomodulatory activity.Despite this widespread belief, data on the immunomodulatory properties and safety of this plant is still lacking. The aim of this work was to determine the toxicity and immunomodulatory properties of the stem bark of Lannea acida in Wistar rats. Methanol extract of Lannea acida A. Rich.was screened for phytochemical properties using standard methods. The acute and the subacute (28-day daily repeated dose) toxicity studies were performed using the OECD Fixed Dose Procedure guideline 420 and OECD guideline 407 respectively. To evaluate the immunomodulatory properties, 12 male and 12 female Wistar rats were pre-sensitised with 0.1ml sheep red blood cell intraperitoneally, and subsequently divided into 4 groups of 6 animals each (3 males, 3 females). The first group served as the control while the remaining three groups received daily oral doses of 250, 500 and 1,000 mg/kg body weight of methanol extract of L. acida, respectivelyfor 14 days.The humoral response (IgM and IgG) to sheep red blood cells was determined by ELISA method and read by microplate reader. The cellular immune response was determined by estimation of the CD4+ and CD8+T-cell counts using flow cytometer, and measuring the delayed type hypersensitivity reaction from the paw thickness of rats given subcutaneous injection of SRBC. The methanol extract of the stem bark of L. acida was found to contain carbohydrate, reducing sugars, alkaloids, glycosides, anthraquinones, triterpenes, cardiac glycosides and tannins; and had an acute lethal dose that was> 3,000 mg/kg. The 28-day oral toxicity study showed a significant decrease (p < 0.05) in the relative organ weight percent of the spleen and kidneys of rats that received a dose of 1,000 mg/kg body weight viii compared with the control; and a significant decrease(p < 0.05) in the serum potassium levels across all the doses compared with the control. There was also a statistically significant increase(p < 0.05) in serum alanine transaminase level at the dose of 500 mg/kg.Histological examination of the organs following 28-day daily oral administration showed hepatic sinusoidal vascular congestion and peri-portal inflammation; splenic red pulp hemorrhage; kidney glomerular necrosis and tubulointerstitial inflammation; and thymocyte depletion in the experimental groups compared to the control.There wassignificant decrease(p < 0.05)in the levels of serum immunoglobulin at the doses of 1,000 mg/kg for IgMand the doses of 500 and 1,000mg/kg for IgG. In conclusion, methanol extract of the stem bark of L. acida has relatively low acute toxicity but when given as a daily dosing for 28 days, it has hepatotoxic, nephrotoxic and immunotoxic effects and hence, potential for multiorgan toxicity when employed for sub-acute and chronic uses.
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