Toxicokinetic Study and Analytical Evaluation of Atractyloside, the Main Toxic Compound of Atractylis gummifera L

Atractylis gummifera L., a plant from the Asteraceae family, is traditionally recognized for its medicinal uses despite its high toxicity when ingested. Poisoning cases, often accidental, are associated with acute liver and kidney damage; however, data on the systemic behavior of its main toxin, atractyloside (ATR), remain limited. This study aimed to investigate the toxicological profile of atractyloside, the primary toxic compound of the plant, through a series of in vivo experiments. The median lethal dose (LD₅₀) was determined in mice using the Karber/Behrens and Miller-Tainter methods, yielding a value of 115 ± 22.16 mg/kg. A toxicokinetic study conducted in Wistar rats following administration of a sub-toxic dose revealed nonlinear kinetics, with a peak plasma concentration (Cmax) of 68.8 mg/L, a half-life (t₁⁄₂) of approximately 90 minutes, and a free fraction of 65%. Protein binding and the role of metabolic activation were further explored using a phenobarbital induction test, which indicated a marked reduction in both Cmax and AUC, suggesting the involvement of ATR and/or its metabolites in toxicity. These findings enhance our understanding of ATR's systemic behavior and could inform clinical management of poisoning cases, particularly given the absence of a specific antidote and the current reliance on symptomatic treatment.