Acute and sub-acute toxicity assessment of methanolic stem bark extract of Khaya anthotheca (Meliaceae) in Wistar rats.

Background: Khaya anthotheca (Meliaceae) is a medicinal plant with a wide range of therapeutic properties attributable mainly to the diverse limonoids it contains. Different parts of the plant are used in traditional health care for treatment of various diseases including candidiasis. However, inadequate information on its safety prompted this particular study.

Methods: Acute toxicity was assessed according to OECD guidelines 425 in female rats administered with single oral doses of 2000 and 5000 mg/kg body weight (b.wt), and monitored for 14 days for any sign of toxicity and mortality. Sub-acute toxicity was evaluated in both male and female rats following OECD guideline 407, and were administered with extract doses of 500, 250 and 125 mg/kg b.wt repeatedly for 28 days. Body weights were measured weekly, while food and water intake were measured daily. Blood for biochemistry, hematology, and organs for histopathology were collected at the end of the experimental period. Data were analyzed using one-way ANOVA followed by Turkey's post hoc tests, and repeated measures ANOVA.

Results: Acute toxicity showed no mortality, with half-lethal dose (LD₅₀) being greater than 5000 mg/kg b.wt. For sub-acute toxicity, both male and female rats presented significant increase in food and water consumption, increased body weight with increasing time and extract doses (p < 0.05). The 500 mg/kg dosed female rats showed significant increase in stomach weights and alanine aminotransferase (ALT), while renal function marker of chloride ions (Cl^-) decreased. Male rats showed dose-dependent significant rise in albumin (ALB) (p = 0.024). For both male and female rats, prolonged use of high extract doses of 250 and 500 mg/kg b.wt for 28 days were toxic to the stomach and liver.

Conclusions: The methanolic stem bark extract of K. anthotheca is practically non-toxic at acute dose of 5000 mg/kg b.wt, and safe for clinical use at low sub-acute doses of 125 mg/kg b.wt. However, long-term administration of high extract doses above 125 mg/kg was toxic to mainly the liver and stomach. Thus, long-term administration of high dosage of methanol stem bark extract of K. anthotheca, and phytomedicine development should be done with cautions of potential side effects.