Effects of thiourea on pulmonary edema, pleural and peritoneal effusions and toxicity in rats pretreated with actinomycin D

Intraperitoneal (i.p.) injections of toxic amounts of thiourea result in pulmonary edema and pleural effusions. Following i.p. injections of sublethal doses a predominance of pleural effusion over pulmonary edema is demonstrated. Pleural effusion resulting from a sublethal dose of thiourea was seen at 6 h, reached a maximum at 12 h, remained constant until 24 h, and disappeared entirely by 48 h. Administration of 2 doses of Actinomycin D (Act D) (100 μg/kg i.p. 12 h apart) was found to produce profuse pleural and peritoneal effusions without causing pulmonary edema. This was in distinct contrast to intratracheal instillation (50 μg/kg 24 h apart) which produced a large amount of pulmonary edema and little pleural effusion. In general, the effects of thiourea in rats pretreated with Act D i.p. were the development of a greater degree of pleural effusion and a lesser degree of pulmonary edema. In addition, a dose-related reduction in the formation of peritoneal effusion was noticed in these rats. Rats pretreated i.p. with Act D were 4 times more sensitive to the lethal effect of thiourea than controls. It is postulated that Act D pretreatment somehow increases capillary permeability which enhances thiourea toxicity.