Bruner L H, Johnson K, Carpenter L J, Roth R A
J Toxicol Environ Health. 1987;21(1-2):205-17. doi: 10.1080/15287398709531013.
Monocrotaline pyrrole (MCTP) is a reactive metabolite of the pyrrolizidine alkaloid monocrotaline. MCTP given intravenously to rats causes pulmonary hypertension and right ventricular hypertrophy. Lesions in lungs after MCTP treatment contain macrophages and neutrophils, which may contribute to the damage by generation of reactive oxygen metabolites. Rats were treated with MCTP and agents known to protect against oxygen radical-mediated damage in acute models of neutrophil-dependent lung injury. Rats received MCTP and deferoxamine mesylate (DF), dimethyl sulfoxide (DMSO), or polyethylene glycol-coupled catalase (PEG-CAT). MCTP/vehicle-treated controls developed lung injury manifested as increased lung weight, release of lactate dehydrogenase into the airway, and sequestration of 125I-labeled bovine serum albumin in the lungs. Cotreatment of rats with DF, DMSO, or PEG-CAT did not protect against the injury due to MCTP. These results suggest that toxic oxygen metabolites do not play an important role in the pathogenesis of MCTP-induced pulmonary injury.
单猪屎豆碱吡咯（MCTP）是吡咯里西啶生物碱单猪屎豆碱的一种活性代谢产物。给大鼠静脉注射MCTP会导致肺动脉高压和右心室肥大。MCTP治疗后的肺部病变含有巨噬细胞和中性粒细胞，它们可能通过产生活性氧代谢产物而导致损伤。在中性粒细胞依赖性肺损伤的急性模型中，用MCTP和已知可预防氧自由基介导损伤的药物对大鼠进行治疗。大鼠接受MCTP和甲磺酸去铁胺（DF）、二甲基亚砜（DMSO）或聚乙二醇偶联过氧化氢酶（PEG-CAT）。MCTP/载体处理的对照组出现肺损伤，表现为肺重量增加、乳酸脱氢酶释放到气道以及肺部滞留125I标记的牛血清白蛋白。用DF、DMSO或PEG-CAT对大鼠进行联合治疗并不能预防MCTP所致的损伤。这些结果表明，毒性氧代谢产物在MCTP诱导的肺损伤发病机制中不起重要作用。
