Assessment of acute and subacute toxic effects of the Saudi folk herb Retama raetam in rats

Background: Retama raetam (RR) fruit is used in traditional Saudi folk medicine as a hypoglycemic herb. However, the potential toxicity of RR has not been fully investigated. The current study aimed to explore the potential acute and subacute toxicities of the methanolic extract of RR fruit in male and female rats. Methods: The extent of acute toxicity of RR was tested 14 days after a single oral dose was administered (250 mg/kg, 500 mg/kg, or 750 mg/kg). Additionally, subacute toxicity was tested 28 days after an oral dose of 250 mg/kg/d, 500 mg/kg/d, or 750 mg/kg/d was administered for 4 weeks. Results: Subsequent to variable dosage testing, oral LD50 of RR was found to be 1995 mg/kg in rats. Oral doses of 500 mg/kg and 750 mg/kg significantly decreased body weight gain. Subacute administration (750 mg/kg) was associated with significant manifestations of toxicity. Additionally, subacute administration of the extract at doses of 500 mg/kg or 750 mg/kg significantly elevated alanine transaminase and aspartate transaminase activities. Hepatotoxicity of RR was confirmed with histopathological findings. Subacute administration of RR (500 mg/kg) showed histopathological changes in the liver as indicated by degenerated hepatocytes and early fibrosis, while a dosage of 750 mg/kg showed congested central vein and vascular degeneration. Moreover, subacute administration of the extract at doses of 250 mg/kg, 500 mg/kg, or 750 mg/kg showed histopathological alterations in rat kidney that ranged from mild interstitial congestion to tubular degeneration. The extract showed positive result in the Ames test. Conclusion: Repeated administration of methanolic extract of RR (250 mg/kg) has a low nephrotoxic subacute toxicity potential, while it might have hepatotoxic, nephrotoxic, and mutagenic effects at higher doses