Acute and sub-chronic toxicities assessment of methanol bark extract of Hypericum roeperianum in rats

Abstract

• Oral acute and sub-chronic toxicities of Hypericum roeperianum methanolic bark extract were evaluated in rats. • No major signs of toxicity were observed in the liver and kidneys. • Slight signs of toxicity were observed at a dose of 1000 mg/kg body weight/day. • Hypericum roeperianum bark is safe at lower doses (250 and 500 mg/kg body weight). The methanolic crude extract of Hypericum roeperianum bark has previously demonstrated interesting cytotoxic properties on panels of human and animal cancer cell lines, involving multi-drug resistant phenotypes. We report here our investigations, which consisted of evaluating the toxicological effects of this plant in experimental animals, Wistar rats. A single oral dose of 5000 mg/kg body weight followed by clinical observations for 14 days was used to assess the acute toxicity of the crude extract of the plant in female rats. For the evaluation of sub-chronic toxicity, repeated oral administration of 250 mg/kg, 500 mg/kg, and 1000 mg/kg body weight was given to the different experimental groups of rats, whereas no treatment was given to the control group. After 28 days of treatment, the animals were sacrificed for hematological and biochemical studies. At the end of the acute toxicity study, we recorded no deaths of rats and no signs of toxicity. Therefore, the median lethal dose (LD 50 ) of H. roeperianum crude extract is greater than 5000 mg/kg body weight. Sub-chronic oral toxicity investigations of the plant showed significant dose-dependent variations in some biochemical parameters, notably LDL cholesterol, creatinine, and alkaline phosphatase, in favour of rats treated with crude extract of H. roeperianum . The hematological profiles showed sometimes significant and sometimes non-significant dose-dependent variations in some parameters. Histopathological analyses revealed slight hepatic inflammation in males treated at 1000 mg/kg body weight. These results suggest that a single high dose of up to 5000 mg/kg of H. roeperianum bark extract is not as toxic as repeated doses of 250, 500, and 1000 mg/kg body weight. However, repeated doses of 1000 mg/kg body weight of H. roeperianum crude extract may show slight signs of toxicity in some organs; it is the case with the liver.