モノクロタリンのラットにおける毒性：肺レチノール減少と肺および肝臓におけるα-トコフェロール上昇

Monocrotaline (MCT) induces lung injury and pulmonary hypertension (PH) by a mechanism that is in part due to oxidative stress. The purpose of this study was to determine how MCT affected nutrient antioxidants retinol and alpha-tocopherol in a rat lung and liver. Rats were fed a purified diet (AIN-93G) one-week prior to a subcutaneous injection of MCT (60 mg/kg) and remained on the diet throughout the study. Three weeks after injection, the animals were euthanized, and the lungs and livers were analyzed for retinol, alpha-tocopherol, phospholipid (PL), and cholesterol content. Lung retinol concentrations were significantly lower in MCT-treated rats, 2.0 ± 1.2 (nmol/g lung) vs. vehicle control (VEH), 5.8 ± 1.4 (P < 0.01). However, liver retinol concentrations were not significantly different, 3.3 ± 1.3 vs. 2.5 ± 0.9 nmol/g liver. Alpha-tocopherol was significantly greater in MCT-treated rats in the lung, 145 ± 24 vs. 99 ± 13 nmol/g lung (P < 0.001), and liver, 107 ± 30 vs. 47.7 ± 4.8 nmol/g liver (P < 0.001). Phospholipid and cholesterol were significantly lower in the lung of the MCT-treated group, but not significantly different in the liver. In conclusion, retinol along with phospholipid, and cholesterol were decreased in the lungs whereas alpha-tocopherol was elevated in the lungs and liver in response to MCT. These findings along with others suggest a novel mechanistic link between MCT-induced oxidative stress, lung vitamin A depletion, inflammation and the impairment of alveolar cell proliferation and repair. Pulmonary retinol is important in the pathogenesis of MCT-induced lung injury.