Evaluation of Subchronic Toxicity of Senecio Cannabifolius Less. Ⅱ After 4-Week Repeated Intragastric Administration in SD rats

OBJECTIVE To evaluate the toxicity of Senecio Cannabifolius Less. Ⅱ, an active ingredient of Senecio Cannabifolius Less., in SD rats following repeated intragastric administration for 4 weeks. METHODS One hundred and twenty SD rats were randomly divided into 4 groups with 30 animals (15 male and 15 female) in each group. Rats were treated orally once a day for 4 weeks with Senecio Cannabifolius Less. Ⅱ (175, 350, 700 mg·kg^-1) or 0.5% CMC-Na as vehicle with a volume of 10 mL·kg^-1. Two-thirds rats in each group were necropsied, and 2 weeks later, the one-third rats in each group were necropsied. During the necropsy, toxicological indexes were detected. RESULTS All the rats survived to scheduled necropsies. Sialorrhea, abdominal distention, anorexia and hypoactivity, inversely related to the duration of dosing, were observed in middle and high dose rats, with a dose-independent manner. Senecio Cannabifolius Less. Ⅱ (350, 700 mg·kg^-1) administration induced a clear trend of declining body weight gain and food intake, compared with the control group. There were no apparent clinical signs of toxicity observed in low dose rats and control rats. High dose rats showed significantly higher ALT, lower TP and ALB compared with control group. Lower thymus and liver, and higher kidney weights occurred mainly in high dose group. Histopathologic examination found that isolated or multiple focal lytic necroses were pronounced in mid-and high-dose rats, at the end of administration. These changes were released after a 2-week drug-free rest period. No other significant changes were observed in electrocardiogram, hematology and bone marrow examination in each group. CONCLUSION The main toxic target of Senecio Cannabifolius Less. Ⅱ is digestive system (increased liver, gastrointestinal tract, body weight and food intake). The toxicity dose of Senecio Cannabifolius Less. Ⅱ was 700, 350 mg·kg^-1.