Dorr R T, Alberts D S, Chen H S
J Pharmacol Methods. 1980 Nov;4(3):237-50. doi: 10.1016/0160-5402(80)90016-9.
Doxorubicin (Adriamycin), a widely used antitumor agent, can occasionally cause severe and protracted local tissue damage if inadvertently extravasated during intravenous injection. An animal model was developed in adult BALB/c mice to experimentally duplicate such human skin toxicity, Intradermal (ID) doxorubicin injections of 0.5, 0.05 and 0.005 mg (per 0.05 ml) provided reproducible, dose-related skin lesions, quantitated with daily measurement of perpendicular diameters of induration, erythema, and ulceration. Maximal lesions developed rapidly (within 3-5 days) and slowly resolved over 30-40 days. There were dose-related increments in peak toxicity levels, total toxicity, and the duration of damage for each parameter (0.5 > 0.05 > 0.005 mg). Subcutaneous (ie, subpannicular) injections, and ID saline control injections did not cause local skin toxicity. A local intervention with ID hydrocortisone (2.5 mg) substantially reduced erythema and induration, and eliminated ulceration only in animals receiving the lower dose (0.05 mg) doxorubicin challenge (p < 0.05). This direct skin toxicity method is compared to reported animal skin toxicity models, and the intervention results are discussed in reference to current toxicity observations in man.
阿霉素（阿德里亚霉素）是一种广泛使用的抗肿瘤药物，如果在静脉注射时不慎外渗，偶尔会导致严重且持久的局部组织损伤。在成年BALB/c小鼠中建立了一种动物模型，以实验性地复制这种人类皮肤毒性。皮内（ID）注射0.5、0.05和0.005毫克（每0.05毫升）阿霉素可产生可重复的、与剂量相关的皮肤损伤，通过每日测量硬结、红斑和溃疡的垂直直径进行定量。最大损伤迅速出现（在3 - 5天内），并在30 - 40天内缓慢消退。每个参数（0.5 > 0.05 > 0.005毫克）的峰值毒性水平、总毒性和损伤持续时间都有与剂量相关的增加。皮下（即皮下脂肪层下）注射以及皮内注射生理盐水对照均未引起局部皮肤毒性。皮内注射氢化可的松（2.5毫克）的局部干预显著减少了红斑和硬结，并且仅在接受较低剂量（0.05毫克）阿霉素攻击的动物中消除了溃疡（p < 0.05）。将这种直接皮肤毒性方法与已报道的动物皮肤毒性模型进行了比较，并参考当前人类的毒性观察结果讨论了干预结果。
