Differentiation of the cardiac and pulmonary toxicity of monocrotaline, a pyrrolizidine alkaloid.
Monocrotaline, given to rats as a 20 mg/l solution in drinking water for 3 weeks, doubled the mass of the right heart and lung. The rise in lung mass preceded that of the heart. These increases were accompanied by increases in the absolute protein content of the two organs, together with increases in the rates of both protein and RNA syntheses. The increase in lung mass was not accompanied by a change in total collagen content, as measured by two independent methods: 4-hydroxyproline content and detergent fractionation. In contrast, the right ventricle showed more than a 4-fold increase in total collagen content. Total pulmonary lipids increased by 86%, but the lipid: protein ratio was unchanged. Right ventricular lipids were unchanged in amount but the lipid: protein ratio fell by 29%. Lung DNA:RNA ratio decreased 49% and right ventricle DNA:RNA ratio decreased 69%, indicating that both of these organs were responding to monocrotaline with hypertrophy. These results suggest that the processes of hypertrophy differ in the two organs: in the lung, there was no fibrosis despite a marked increase in dry weight, while right ventricular hypertrophy was characterized by increased collagen deposition. There was no alteration in the left ventricle in any of the parameters investigated.
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D050356:Lipid Metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009929:Organ Size / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011763:Pyrrolizidine Alkaloids; D012313:RNA; D016686:Monocrotaline; D003094:Collagen; D004247:DNA; D006909:Hydroxyproline