Effect of diclofenac and naproxen on drug-metabolizing enzymes in mice

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac and naproxen on xenobiotic-metabolizing enzymes was studied in male Swiss mice given the drugs in their diet. Diclofenac at levels of 25, 75, and 375 ppm, and naproxen at 150, 500, and 1,500 ppm, were given for a period of 4 weeks. Control animals consumed a similar diet deprived of the test NSAIDs. Feeding of NSAIDs did not affect the activity of arylhydrocarbon hydroxylase, whereas the level of cytochrome P-450 (P-450) was significantly decreased in liver and lungs of the animals. The maximum decline in content of the enzyme was found at the largest dose of NSAIDs. On the other hand, the activity of glutathione-S-transferase (CST) was significantly increased in the two organs by both drugs. However, hepatic activity of the enzyme after induction by 375 ppm diclofenac was almost 1.37 fold greater in comparison to that after induction by 1,500 ppm naproxen. In lungs, this ratio was found to be 1.76. Like GST, reduced glutathione (GSH) levels in the liver and lungs of the animals were also significantly increased. The maximum increase in GSH in lungs elicited by the two NSAIDs was similar. The results of this study indicate that diclofenac might prove to be a better chemopreventive agent against xenobiotics because of the higher induction of GST activity by it.