Acute (14-Day) and Subchronic (90-Day) Toxicity Evaluation of the Dried Fruit Spice Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) in Male and Female Wistar Rats.

Abstract

Background: Xylopia aethiopica (XAE) fruit (Ethiopian pepper) is a culinary spice widely used in African countries. It has numerous biological properties including potent anticancer properties; however, there is a lack of data on its safety, which justifies this study.

Methods: Animals were administered a unique dose of 2000 mg/kg for the acute (14-day) toxicity and three doses (75, 150, and 300 mg/kg BW) of the subchronic (90-day) oral toxicity of ethanol dry fruit of XAE extract guideline numbers 423 and 408, respectively. Behavioral, morphological (body weight and relative weight of the organs), biochemical, hematological, and histological parameters of toxicological interest were evaluated with organs, such as the lung, liver, kidney, breast, and testes, just to name a few.

Results: An LD₅₀ > 2000 mg/kg was found after an acute exposure to XAE in young female rats. After 90 days of administration, XAE induced no significant changes in body weight and relative weights of the organs. In both female and male rats, no significant changes were observed in the tested biochemical parameters (creatinine, total proteins, triglycerides, total cholesterol, HDL, LDL, ALT, AST, and urea), except for the bilirubin levels, which slightly decreased in males at a dose of 300 mg/kg BW. No change was observed in the histological sections of organs of interest in toxicology (spleen, lungs, kidneys, liver, and heart) as well as in the reproductive organs (vagina, uterus, and ovary for females and testes, seminal vesicle, prostate, and epididymis for males). A significant decrease was observed in the level of hematological parameters, such as platelet levels in both female (p ≤ 0.001) and male (p ≤ 0.01) Wistar rats when compared to the control. This decrease in platelet concentration observed in experimental rats suggests that XAE may induce thrombocytopenia, possibly through an adverse effect on thrombopoiesis.

Conclusion: Taken altogether, the observations therefore showed that long-term administration of XAE dry fruit extract might induce thrombocytopenia and anemia, particularly at higher doses, warranting caution regarding long-term use.