Okazaki S, Yamazaki E, Tamura K, Hoshiya T, Anabuki K, Tanaka H, Tanaka G
Bozo Research Center Inc., Tokyo, Japan.
J Toxicol Sci. 1992 Nov;17 Suppl 3:1-48. doi: 10.2131/jts.17.supplementiii_1.
The toxicity of Prednisolone farnesylate (PNF), a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF was injected subcutaneously at doses of 0.03, 0.3, 3 and 30 mg/kg/day for 13 weeks. In addition, 18.7 mg/kg/day prednisolone (PN), which is approximate to 30 mg/kg/day PNF in prednisolone molarity, was also administered to the rat for comparison. The results are summarized as follows: 1. All animals from the PN 18.7 mg/kg/day group, and four(4) out of ten(10) males and three(3) out of ten(10) females from the PNF 30 mg/kg/day group died having shown weakened condition such as unkempt fur and emaciation. Histopathologically, systemic suppurative inflammation, as shown by pyeronephritis and abscess formation in many organs and tissues, was observed and it was considered that the administration of steroid induced weakened condition and systemic suppuration which resulted in death. In addition, atrophy was noted in the adrenal glands, lymphatic organs and skin, and histopathological lesions were also observed in the lungs, liver, pancreatic islets, bone, bone marrow and mammary glands. 2. Surviving animals in the PNF 30 mg/kg/day group showed almost the same changes as those observed in the dead animals that died. Hematological examination revealed an anemic change and a decrease in lymphocytes with an increase in segmented neutrophils and eosinophils. In the urinalysis and blood chemistry, the changes suggesting damages to the liver and kidneys were mainly observed. 3. In the PNF 3 and 0.3 mg/kg/day groups, several changes such as atrophy of the adrenal glands, lymphatic organs and skin were noted in a dose dependent manner. 4. In the PNF 0.03 mg/kg/day group, ther were no toxic signs. 5. Based on these results, it was concluded that the overt toxic dose of PNF was 0.3 mg/kg/day and the non-toxic dose was 0.03 mg/kg/day in the present study.
对合成糖皮质激素法尼酸泼尼松龙（PNF）在Sprague-Dawley大鼠中的毒性进行了研究。以0.03、0.3、3和30mg/kg/天的剂量皮下注射PNF，持续13周。此外，还以18.7mg/kg/天的泼尼松龙（PN）（其泼尼松龙摩尔浓度近似于30mg/kg/天的PNF）对大鼠进行给药以作比较。结果总结如下：1. 18.7mg/kg/天PN组的所有动物，以及PNF 30mg/kg/天组10只雄性中的4只和10只雌性中的3只，在表现出诸如皮毛凌乱和消瘦等虚弱状况后死亡。组织病理学上，观察到全身性化脓性炎症，如许多器官和组织中的肾盂肾炎和脓肿形成，并且认为类固醇的给药导致了虚弱状况和全身性化脓，进而导致死亡。此外，肾上腺、淋巴器官和皮肤出现萎缩，并且在肺、肝、胰岛、骨、骨髓和乳腺中也观察到组织病理学病变。2. PNF 30mg/kg/天组中的存活动物表现出与死亡动物几乎相同的变化。血液学检查显示有贫血变化，淋巴细胞减少，分叶中性粒细胞和嗜酸性粒细胞增多。在尿液分析和血液化学检查中，主要观察到提示肝和肾受损的变化。3. 在PNF 3和0.3mg/kg/天组中，观察到肾上腺、淋巴器官和皮肤等出现一些变化，且呈剂量依赖性。4. 在PNF 0.03mg/kg/天组中，未出现毒性迹象。5. 根据这些结果得出结论，在本研究中，PNF的明显毒性剂量为0.3mg/kg/天，无毒剂量为0.03mg/kg/天。
