Chang L W, Yang C M, Chen C F, Deng J F
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock 72205.
Biomed Environ Sci. 1992 Dec;5(4):293-302.
Young male rats were orally intubated with podophyllotoxin: Group I, control animals, orally fed with vehicle only; Group II, fed with an initial dose of 5 mg.kg-1 b.w., followed by a daily dose of 1.67 mg.kg-1 b.w. for 7d. Group III, fed with an initial dose of 15 mg.kg-1 b.w., followed by a daily dose of 5 mg.kg-1 b.w. for 7d. All animals were sacrificed 72 h after the last dosing. Histopathological examination revealed dose-related fatty change of the liver, atrophy and degenerative changes of the intestinal epithelial linings and testicular seminiferous tubules. Depletion of the pancreatic acinar cell granules was also apparent in the Group III animals. No pathology, however, was observed in the kidneys. The present study demonstrated for the first time degenerative changes in the liver, intestine, testis, and pancreas of animals ingested podophyllotoxin. These pathological changes correlate well with the clinical signs/symptoms of abnormal liver function, abdominal pain and diarrhea, and reduced serum amylase in humans poisoned by podophyllum. Inhibition of protein synthesis and mitosis (disruption of microtubules) are believed to be the underlying mechanisms of these changes observed in the animals intoxicated by podophyllotoxin.
第一组为对照动物，仅经口给予赋形剂；第二组，初始剂量为5mg.kg-1体重，随后每日剂量为1.67mg.kg-1体重，持续7天。第三组，初始剂量为15mg.kg-1体重，随后每日剂量为5mg.kg-1体重，持续7天。在最后一次给药72小时后处死所有动物。组织病理学检查显示肝脏出现剂量相关的脂肪变化、肠上皮衬里和睾丸生精小管萎缩及退行性变化。在第三组动物中胰腺腺泡细胞颗粒的减少也很明显。然而，在肾脏中未观察到病理学变化。本研究首次证明摄入鬼臼毒素的动物肝脏、肠道、睾丸和胰腺出现退行性变化。这些病理变化与人类因鬼臼中毒导致的肝功能异常、腹痛和腹泻以及血清淀粉酶降低的临床体征/症状密切相关。蛋白质合成和有丝分裂的抑制（微管破坏）被认为是在鬼臼毒素中毒动物中观察到的这些变化的潜在机制。
