Pollack G M, Browne J L, Marton J, Haberer L J
School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Drug Metab Dispos. 1991 Jan-Feb;19(1):130-4.
Traumatic injury to both hard and soft tissue has been associated with a decrease in the rate of hepatic drug metabolism. The mechanism(s) underlying this phenomenon have yet to be determined, but may involve substances released from damaged tissues or activation of the adrenocortical axis secondary to stress. To determine whether a generalized stress response is involved in the trauma-induced perturbations of xenobiotic metabolism, rats were exposed to atraumatic stress for a period of 21 days prior to determining the disposition of antipyrine (an in vivo marker for the hepatic mixed-function oxidase system) and indocyanine green (a tricarbocyanine dye often used as an in vivo marker of active hepatic uptake). Exposure to stress resulted in a significant decrease in the systemic clearance of antipyrine, suggesting a stress-induced inhibition of hepatic oxidation. In addition, the stressed animals evidenced a decreased rate of uptake of indocyanine green by the liver, an apparent decrease in the storage of the dye within the liver, and a decreased hepatic clearance of indocyanine green (presumably due to a decrease in the KM for biliary transport). These observations suggest that atraumatic stress affects several processes involved in the hepatobiliary disposition of xenobiotics.
硬组织和软组织的创伤性损伤与肝脏药物代谢速率降低有关。这一现象背后的机制尚未确定，但可能涉及受损组织释放的物质或应激继发的肾上腺皮质轴激活。为了确定全身应激反应是否参与创伤诱导的外源性物质代谢紊乱，在测定安替比林（肝脏混合功能氧化酶系统的体内标志物）和吲哚菁绿（一种常用于肝脏主动摄取体内标志物的三碳菁染料）的处置情况之前，将大鼠暴露于非创伤性应激21天。应激导致安替比林的全身清除率显著降低，提示应激诱导的肝脏氧化抑制。此外，应激动物肝脏对吲哚菁绿的摄取速率降低，染料在肝脏内的储存明显减少，吲哚菁绿的肝脏清除率降低（可能是由于胆汁转运的米氏常数降低）。这些观察结果表明，非创伤性应激会影响外源性物质肝胆处置所涉及的多个过程。
