吡非尼酮灌胃小鼠的急性光毒性

The acute phototoxicity of pirfenidone in mice

目的:研究一种新的抗纤维化试验药物吡非尼酮(PFD)灌胃(ig)小鼠的急性光毒性反应。方法:设小鼠igPFD100、200、400mg·kg-1·d-13个剂量组;2个溶媒对照组:0.5%羧甲基纤维素钠(CMC-Na)溶液对照组,生理盐水对照组;盐酸氯丙嗪注射液30mg·kg-1·d-1阳性对照组、空白对照组共7个组,每组10只小鼠,连续给药7d后,于第7天给药15min后,用黑光灯(220V,40W,波长320~450nm,峰值360nm,滤去致正常组织红斑的290~340nm波长)连续照射24h,观察小鼠igPFD后两耳有无红斑、水肿、皮肤瘙痒和色素沉着甚至局部坏死、溃烂、表皮脱落等光毒反应,共严密观察7d。结果:阳性对照组小鼠双耳出现中度充血、水肿等反应,3d后症状消失。PFD各剂量组和2个溶媒对照组、空白对照组小鼠在长波紫外线照射后7d内均未出现急性光毒反应。结论:连续7digPFD小鼠未出现急性光毒反应。

Objective: To study the acute phototoxicity of a new drug——pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone, PFD) in mice, which had beneficial effects for the treatment of fibrotic diseases including renal, liver and pulmonary fibrosis and multiple sclerosis. Methods: The mice were radomly divided into 7 groups. There were 10 mice in each group. The mice of three groups were administrated (ig) with 100, 200, 400 mg·kg^(-1)·d^(-1 ) of pirfenidone, respectively. Two groups were given 0.5% solution of sodium carboxymethyl cellulose or saline solution as solvent control groups. One group was given subcutaneous injection of chlorpromazine hydrochloride 30 mg·kg^(-1)·d^(-1 ) as positive control group. Another group served as blank control. All mice were given above substances for 7 days. On seventh day, 15 min after treatment, the dorsal surfaces of mouse ears were exposed to continuous irradiation of black light (220 V, 40 W, wave length 320-450 nm, maximum wave length 360 nm, excluding wave length 290-340 nm) for 24 h. Then the mouse ears were observed if there were erythema, oedema, titillation or chromatosis, local necrosis, inflammation and excoriation and other phototoxic reactions in the experimental animals for 7 days. Results: The reaction of moderate hyperemia and oedema appeared on the mouse ears of positive control group and disappeared after 3 days. There were no marked changes in the mice of 3 pirfenidone groups, 2 solvent control groups and the blank group during 7 days after ultraviolet irradiation. The acute phototoxicity was not found in mice after pirfenidone ig administration. Conclusion: Acute phototoxicity of pirfenidone in mice was not observed.