Role of JNK in the Regulation of Xenobiotic Metabolizing Function of Hepatocytes

We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension. The results show the promise of studying modifiers of activity of intracellular signaling molecules (in particular, mitogen-activated protein kinases) to develop a fundamentally new approach to control the transformation of xenobiotics and to create a new class of pharmaceutical, target regulators of drugs metabolism.

Automated summary

The study focused on the role of JNK in regulating the metabolism of xenobiotic venlafaxine by liver cells in vitro, showing its inhibitory effect on the biotransformation of the psychotropic agent. Adding a JNK inhibitor to a liver homogenate containing the antidepressant led to enhanced and accelerated formation of the active metabolite. These results suggest the potential of studying intracellular signaling molecules to develop a novel approach for controlling xenobiotic transformation and creating pharmaceutical regulators of drug metabolism.