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首页> 外文期刊>Life sciences >L-NAME prevents in vivo the inactivation but not the down-regulation of hepatic cytochrome P450 caused by an acute inflammatory reaction.
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L-NAME prevents in vivo the inactivation but not the down-regulation of hepatic cytochrome P450 caused by an acute inflammatory reaction.

机译：L-NAME可防止体内急性炎症反应引起的肝细胞色素P450失活，但不能下调。

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摘要

A turpentine-induced inflammatory reaction (TIIR) down-regulates multiple isoforms of hepatic cytochrome P450 (P450) and increases microsomal lipid peroxidation. Since the synthesis of nitric oxide (NO*) is stimulated by inflammatory reactions, and NO* can depress the P450, it was of interest to investigate in vivo whether L-NAME and theophylline, by its anti-inflammatory properties, could prevent the depression of P450 caused by a TIIR. Control and rabbits with a TIIR received L-NAME for 72 h, and the activity of P450 was assessed in vivo and in vitro. In vivo, TIIR reduced theophylline systemic clearance by 50% (p<0.05), P450 total content by 67%, and the amount of CYP1A1/2 proteins by around 60% (p<0.05). L-NAME partially prevented the decrease in theophylline systemic clearance and in P450 total content, as well as the increase in lipid peroxidation; however, L-NAME did not hinder CYP1A1/2 proteins down-regulation. L-NAME did not modify the in vitro ability of the serum of rabbits with TIIR to decrease P450 activity, suggesting that the effect of L-NAME is not associated to a decrease in serum mediators. As assessed by the concentration in seromucoids, theophylline did not modify the severity of the inflammatory reaction, nor did it prevent the decrease in P450 activity. In conclusion, a TIIR down-regulates and reduces P450 activity, decrease that is at least in part mediated by NO*; theophylline does not prevent TIIR-induced P450 decrease in activity.
机译：松节油诱导的炎症反应（TIIR）下调肝细胞色素P450（P450）的多种同工型，并增加微粒体脂质过氧化作用。由于炎症反应会刺激一氧化氮（NO *）的合成，并且NO *可以抑制P450，因此有必要在体内研究L-NAME和茶碱的抗炎特性是否可以预防抑郁症由TIIR引起的P450的变化。对照组和具有TIIR的兔子接受L-NAME治疗72小时，并在体内和体外评估P450的活性。在体内，TIIR使茶碱全身清除率降低了50％（p <0.05），P450总含量降低了67％，CYP1A1 / 2蛋白的量降低了约60％（p <0.05）。 L-NAME部分阻止了茶碱全身清除率的降低和P450总含量的减少以及脂质过氧化作用的增加;但是，L-NAME不会阻止CYP1A1 / 2蛋白的下调。 L-NAME并未改变TIIR兔血清降低P450活性的体外能力，这表明L-NAME的作用与血清介质的降低无关。通过血清中类固醇的浓度评估，茶碱既不会改变炎症反应的严重性，也不会阻止P450活性的降低。总之，TIIR下调并降低了P450活性，这种降低至少部分是由NO *介导的。茶碱不能阻止TIIR诱导的P450活性降低。

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