Innate and drug-induced resistance to acute lung damage caused in rats by alpha-naphthyl thiourea (ANTU) and related compounds.
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.
D000367:Age Factors; D000818:Animals; D004351:Drug Resistance; D005260:Female; D008168:Lung / Q000473:pathology; D009929:Organ Size; D010996:Pleural Effusion / Q000032:analysis; D011193:Potassium Iodide / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D011654:Pulmonary Edema / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D013618:Tachyphylaxis; D013890:Thiourea / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D013965:Thyroidectomy
D011506:Proteins; D011193:Potassium Iodide; D013890:Thiourea