TOXICOLOGICAL EFFECTS OF ETHANOL EXTRACT OF Picralima nitida STEM BARK IN MALE SPRAGUE-DAWLEY RATS

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ABSTRACT

Picralima nitida (Apocynaceae) is commonly used in West African traditional medicine for various therapeutic purposes. This experimental study evaluated the safety of ethanol extract of Picralima nitida stem bark by assessing its potential toxicity after acute and sub-chronic administration in Sprague-Dawley rats. For the acute toxicity study, Lorke’s method was used. Fifteen male Sprague-Dawley rats with an average weight of 168 ± 9.79g were  divided into two phases.In Phase I, twelve rats were divided into four groups of three rats each. Groups II, III, and IV received single oral doses of 10 mg/kg, 100 mg/kg, and 1000 mg/kg body weight of the extract, respectively, while Group I served as the control. In Phase II, three additional rats were each administered single doses of 1600 mg/kg, 2900 mg/kg, and 5000 mg/kg body weight of the extract. Behavioral changes and mortality were monitored over 14 days. In the sub-chronic study, thirty male Sprague-Dawley rats, with an average weight of 197 ± 3.68g, were divided into six groups of five rats each. Group I (control), while Groups II to VI  received 150 mg/kg, 300 mg/kg, 800 mg/kg, 2000 mg/kg and 5000 mg/kg body weight of extractdaily for 28 days. The weight of the animals and fasting blood glucose were determined weekly for 28 days.On the 28th day, the rats were fasted for 12 hours before euthanasia. Blood samples were collected for biochemical analysis, while the liver, heart, kidney, and pancreas were harvested for histopathological evaluation. All data were analyzed using IBM SPSS software. Statistical comparisons were performed using one-way analysis of variance (ANOVA), followed by a post-hoc test to determine significant differences among groups. In the acute toxicity study, the rats tolerated the administered doses. However, behavioral changes, particularly sluggishness, were observed at higher doses (≥1600 mg/kg). In the sub-chronic study, the extract demonstrated a glucose-lowering effect, with the 150 mg/kg dose showing the most significant and consistent reduction throughout the experiment. Lower doses also promoted weight gain, enhanced insulin secretion, and stimulated pancreatic duct proliferation.Additionally, lower doses significantly reduced non-HDL cholesterol and decreased the triglyceride-to-HDL (TG/HDL) cholesterol ratio.At higher doses (2000 mg/kg and 5000 mg/kg), adverse metabolic effects were observed, including a reduction in weight gain, increased liver weight (p < 0.05), elevated sodium levels   (p < 0.05), increased triglycerides (p < 0.05), and an increase in non-HDL cholesterol. Histopathological analysis of the liver revealed inflammation in the portal region, which appeared to decrease at higher extract concentrations. Notably, no significant toxic effects were observed in the heart, kidney, or pancreas.In conclusion, the ethanol extract of Picralima nitida stem bark appears to be non-toxic at lower doses but may pose risk at higher doses. While it may be considered safe for consumption at lower doses, caution is advised for higher doses unless the therapeutic benefits outweigh the potential risks.

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