Acute and subacute toxicity of ethanol leaf extract of Urtica simensis Hochst. ex A. Rich in rats.

Urtica simensis is a native nutraceutical herb in Ethiopia, but its safety of repeated oral intake has not been reported yet. This study aimed to evaluate acute and subacute toxicity of ethanol leaf extract of U. simensis in rats. The median lethal dose (LD₅。) was determined using OECD guideline 425. Sixty rats (30 males and 30 females) were assigned to six groups per OECD guideline 407. Groups I-III received 250, 500 and 1000 mg/kg of U. simensis ethanol leaf extract daily for 4 weeks, while Group IV received distilled water. The satellite 1000 mg/kg and satellite control groups were monitored for additional 2 weeks. Clinical signs, food intakes and body weights were recorded. After 4 weeks, rats were euthanized for organ weight, blood chemistry and histopathological evaluations. The results revealed that the LD₅。 exceeded 5 g/kg. No adverse effects were observed at 250 mg/kg. However, 1000 mg/kg dose caused significant weight gain in both male and female rats. Doses of 500 and 1000 mg/kg significantly elevated alanine aminotransferase in both sexes of rats. Male rats given 1000 mg/kg showed significantly increased serum creatinine, while females exhibited reduced hemoglobin. Some female rats treated with 1000 mg/kg had liver parenchymal necrosis, kidney glomerular distortion and spleen white pulp depletion. In conclusion, 500 and 1000 mg/kg of leaf extract caused significant weight gain, biochemical changes and histopathological alterations in the liver, kidney and spleen of some female rats. Therefore, caution should be exercised when considering repeated oral intake of U. simensis leaves.