Dunbar J R, DeLucia A J, Acuff R V, Ferslew K E
Department of Surgery, Quillen-Dishner College of Medicine, East Tennessee State University, Johnson City 37614.
Toxicol Appl Pharmacol. 1988 Jun 30;94(2):221-6. doi: 10.1016/0041-008x(88)90263-3.
The effects of paraquat (PQ) on lung putrescine, spermidine, and spermine levels, and ornithine decarboxylase (ODC) activity were assessed in rats after 7 days of iv infusion of the herbicide via osmotic minipump. Paraquat administration at a rate of 250 nmol/hr [673 +/- 40 nmol/kg/hr (n = 15)] had no effect on these parameters. In contrast, significant (p less than 0.05) elevations in lung putrescine (407% of control), spermidine (202% of control), and ODC activity (174% of control were measured in lungs of rats given 500 nmol PQ/hr [1.31 +/- 0.53 mumol/kg/hr (n = 14)]. Since evidence of lung damage was, likewise, observed only in the high-dose PQ rats, these changes in polyamine metabolism could have been a nonspecific response to PQ-induced lung injury rather than a direct biochemical effect of PQ. The results suggest that stimulation of polyamine biosynthesis may play an important role in PQ-induced lung injury. This role may involve regulation of repair mechanisms or, conversely, the polyamines may actually mediate PQ-induced fibrotic changes in the lung.
通过渗透微型泵静脉输注百草枯7天后,评估百草枯(PQ)对大鼠肺组织中腐胺、亚精胺和精胺水平以及鸟氨酸脱羧酶(ODC)活性的影响。以250 nmol/小时[673±40 nmol/(千克·小时)(n = 15)]的速率给予百草枯对这些参数没有影响。相比之下,在给予500 nmol PQ/小时[1.31±0.53 μmol/(千克·小时)(n = 14)]的大鼠肺组织中,腐胺(对照的407%)、亚精胺(对照的202%)和ODC活性(对照的174%)显著(p<0.05)升高。由于同样仅在高剂量PQ大鼠中观察到肺损伤的证据,这些多胺代谢变化可能是对PQ诱导的肺损伤的非特异性反应,而不是PQ的直接生化作用。结果表明,多胺生物合成的刺激可能在PQ诱导的肺损伤中起重要作用。这一作用可能涉及修复机制的调节,或者相反,多胺实际上可能介导PQ诱导的肺纤维化变化。