叶下珠提取物对Beagle犬长期毒性实验研究

A 26 Weeks Oral Toxicity of Extracts of Phyllanthus urinaria L.in Beagle Dogs

目的研究连续口服给予叶下珠提取物对Beagle犬产生的毒性反应。方法叶下珠提取物125、250、500mg·kg-1(低、中、高剂量)连续灌胃给药26wk,于给药26wk及停药6wk时取部分犬进行血液学指标、血液生化学指标、尿液指标、病理组织学检查。结果高剂量组Beagle犬出现食量减少、间歇性呕吐等症状。与空白对照组比较,中、高剂量在给药结束时导致Beagle犬ALT、AST、ALP、T-Bil、BUN、γ-GT等血液生化学指标明显升高(P<0.05或P<0.01),停药6wk后,以上指标均恢复正常。给药结束时,高剂量组Beagle犬尿液出现蛋白质和胆红素阳性。病理检查显示,中、高剂量均可导致Beagle犬肝脏和肾脏实质脏器出现可逆性组织病理学改变。结论长期大剂量口服给予叶下珠提取物,可导致Beagle犬出现肝脏和肾脏功能以及病理组织学可逆性改变。

Objective To observe the long-term toxicity of the extracts of Phyllanthus urinaria L. in dogs by repeated oral administration. Method Daily doses of extracts at 125 mg＇kg-I, 250 mg＇kg-1 and 500 mg＇kg-1 for 26 weeks were used for low, mid, and high dose group, respectively. Examinations including haematological indexes, biochemical indexes, urinalysis and histopathology were performed at 26 weeks during the administration, and 6 weeks after the withdrawal, respectively. Results The dogs in the high group showed a reduction in the food consumption and appeared interval disgorging during the administration. The levels of ALT, AST, ALP, T-Bil, BUN and ＂y-GT in high group were significantly higher than those in control group at 26 weeks after administration（P〈0.05）. Those changed blood biochemistery indexes regained normal at 6 weeks after withdrawal. Hematology data did not show treatment related change in all of the dogs. The high group dogs showed positive protein and bilirubin in the urine at terminal sacrifice. The liver and kidney of dogs in high and mid group appeared reversible pathological changes.Conclusion Repeated oral administration of the extracts of Phyllanthus urinaria L. at high dose could lead to reversible damage to liver and kidney function and pathology in dogs.