Allais Linda, Condevaux Fabienne, Fant Pierluigi, Barrow Paul C
MDS Pharma Services, 329 Impasse du Domaine Rozier, Les Oncins, 69210 Saint-Germain sur l'Arbresle, France.
Reprod Toxicol. 2009 Sep;28(2):230-8. doi: 10.1016/j.reprotox.2009.04.012. Epub 2009 May 4.
The pups from 32 litters of SD rats were given 0, 1, 3 or 10mg/kg-d of cyclosporin by oral gavage from 4 to 28 days of age. 10mg/kg-d resulted in a persistent impairment of the primary antibody response at 10 weeks of age. Indications of systemic toxicity, including the death of 10/64 pups and severely depressed weight gain, were also observed at this dose level. Arteriopathy of the heart and tubular basophilia and edema in the cortico-medullary region of the kidney were observed at 3 and 10mg/kg-d. In conclusion, while pharmacological effects were seen at all dose levels, the adverse effects of cyclosporin on the development of the immune system in the rat only occurred at a dose level that also induced systemic toxicity.
从4日龄至28日龄，对32窝SD大鼠的幼崽通过灌胃给予0、1、3或10mg/kg·d的环孢素。10mg/kg·d导致10周龄时初次抗体反应持续受损。在该剂量水平还观察到全身毒性迹象，包括64只幼崽中有10只死亡以及体重增加严重受抑。在3mg/kg·d和10mg/kg·d剂量下观察到心脏动脉病变以及肾皮质 - 髓质区域的肾小管嗜碱性变和水肿。总之，虽然在所有剂量水平均可见药理作用，但环孢素对大鼠免疫系统发育的不良反应仅在诱导全身毒性的剂量水平出现。
