Effect of chronic morphine treatment on time-course of free radical processes

The state of an enzymatic component of the antioxidant system, intensity of lipid peroxidation (LPO) in the liver, and the level of blood plasma nitric oxide were investigated in rats subjected to chronic morphine intoxication. Initially male Wistar rats were treated with introperitoneal injections of 1% morphine hydrochloride twice a day. The daily dose of morphine was gradually increased from 10 mg/kg (1-2 days) to 20 mg/kg (3-4 days), and up to 40 mg/kg starting at the fifth day. Animals were subdivided into three groups receiving morphine injections for 7, 14 and 21 days. Control animals were treated with the same volume of 0.9% NaCl injected intraperitoneally. Chronic morphine treatment was accompanied by the marked inhibition of the peroxide-utilizing antioxidants in liver. This created favorable conditions for H^sub 2^O^sub 2^ toxicity and triggered LPO chain reactions. However, low level of thiobarbituric acid reactive products suggests involvement of some scavenger(s) of H^sub 2^O^sub 2^, which inhibits hydrogen-peroxide induced free radical processes. In vitro experiments suggest that morphine may be involved into reduction of H^sub 2^O^sub 2^ level, whereas administration of morphine to rats may also employ nitric oxide as the scavenger of reactive oxygen species.[PUBLICATION ABSTRACT]