van den Brenk H A, Kelly H, Stone M G
Br J Exp Pathol. 1976 Dec;57(6):621-36.
During the 3rd and 4th weeks of life rats were highly resistant to the toxic effects of alpha-naphthyl thiourea (ANTU) and of thiourea and its derivatives but toxicity developed rapidly during the following 2 weeks. Marked resistance to lung damage by toxic thioureas could be induced in older, mature rats by pretreatment with the toxic agent itself (tachyphylaxis), with other toxic and non-toxic antithyroid drugs or with iodine or iodide--even if the rats were pretreated at an early age before susceptibility to the agent developed. ANTU-tachyphylaxis was dose-dependent. Total thyroidectomy did not affect either lung damage induced by ANTU or the resistance due to tachyphylaxis or to pretreatment with iodide or the antithyroid drugs thiourea, 1-ethyl-1-phenyl thiourea or propyl thiouracil. Neither total nor medullary adrenalectomy affected ANTU toxicity. Marked resistance to ANTU-induced lung damage was induced in rats by pretreatment with either an activator (3-4 benzypyrene) or an inhibitor (SKF 525-A) of drug-metabolizine mixed-function microsomal enzyme systems; the inhibitor, sodium phenobarbitone, had no significant effect on toxicity. The sulphydryl compound, AET, induced marked resistance to ANTU; cysteine was less effective. Neither autonomic blockade with nicotine and atropine nor actinomycin D had significant effects on toxicity to ANTU. The acute pulmonary oedema induced in rats by high pressure oxygen, chemical convulsants, pressor agents and ammonium sulphate differed in many respects from that induced by toxic thioureas; it was typically haemorrhagic in nature, did not result in significant pleural effusion, did not exhibit tachyphylaxis, and was not influenced by pretreatment with iodide or derivatives of thiourea.
在出生后的第3和第4周，大鼠对α-萘基硫脲（ANTU）、硫脲及其衍生物的毒性具有高度抗性，但在随后的2周内毒性迅速发展。通过用毒性药物本身（快速耐受性）、其他毒性和非毒性抗甲状腺药物或碘或碘化物进行预处理，可在年龄较大的成熟大鼠中诱导出对毒性硫脲所致肺损伤的显著抗性——即使大鼠在对该药物易感性出现之前的早期就进行了预处理。ANTU快速耐受性呈剂量依赖性。全甲状腺切除既不影响ANTU所致的肺损伤，也不影响因快速耐受性或用碘化物或抗甲状腺药物硫脲、1-乙基-1-苯基硫脲或丙基硫氧嘧啶预处理所产生的抗性。全肾上腺切除或肾上腺髓质切除均不影响ANTU毒性。通过用药物代谢混合功能微粒体酶系统的激活剂（3,4-苯并芘）或抑制剂（SKF 525-A）对大鼠进行预处理，可诱导出对ANTU所致肺损伤的显著抗性；抑制剂苯巴比妥钠对毒性无显著影响。巯基化合物AET可诱导对ANTU的显著抗性；半胱氨酸的效果较差。用尼古丁和阿托品进行自主神经阻滞以及放线菌素D对ANTU毒性均无显著影响。高压氧、化学惊厥剂、升压剂和硫酸铵在大鼠中诱导的急性肺水肿在许多方面与毒性硫脲诱导的不同；其典型特征是出血性，不会导致明显的胸腔积液不会出现快速耐受性，且不受碘化物或硫脲衍生物预处理的影响。
