Modulation of the pentose phosphate pathway alters phase I metabolism of testosterone and dextromethorphan in HepG2 cells.

ABSTRACT:

Aim

The pentose phosphate pathway (PPP) is involved in the activity of glucose-6-phosphate dehydrogenase (G6PD) and generation of NADPH, which plays a key role in drug metabolism. The aim of this study was to investigate the effects of modulation of the PPP on drug metabolism capacity in vitro.

Methods

A pair of hepatic cell lines, ie, the cancerous HepG2 cells and normal L02 cells, was used. The expression of CYP450 enzymes, p53 and G6PD in the cells were analyzed. The metabolism of testosterone (TEST, 10 μmol/L) and dextromethorphan (DEM, 1 μmol/L), the two typical substrates for CYP3A4 and CYP2D6, in the cells was examined in the presence of different agents.

Results

Both the expression and metabolic activities of CYP3A4 and CYP2D6 were considerably higher in HepG2

SUBMITTER: Xiao WJ 

PROVIDER: S-EPMC4326794 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature