Nevirapine modulation of paraoxonase-1 in the liver: An in vitro three-model approach

Twelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death

“…As with previously published in vitro studies involving NVP, we had to use high, supra-therapeutic concentrations to observe any cell death with NVP. ,, We did see a reduction in C57BL/6J hepatocyte death using 12-D 3 NVP as compared to NVP, though the clinical implications of this degree of change are difficult to ascertain (from 52.6% of cells dead/dying with NVP to 36.8% with 12-D 3 NVP). Though the observed reduction suggests that 12-OHNVP formation may play a role in hepatocyte death with NVP, given the supra-therapeutic concentrations needed to stimulate cell death and the degree of decrease observed, future experimentation is needed.…”

Oxidative stress and genotoxicity of co-exposure to chlorpyrifos and aflatoxin B1 in HepG2 cells

“…PA was widely used as a substrate to determine paraoxonase 1 (PON1)–arylesterase activity and its hydrolysis led to the formation of acetic acid and phenol, as previously described (Marinho et al, 2016). After cells (3 × 10 4 cells/well) were incubated with DMEM culture medium without phenol red for 24 h, the supernatant was diluted in 0.9% sodium chloride (1:2).…”

Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence

“…This is the case of rutaecarpine (see section of CYP1A1 inhibitors ). A plausible explanation is that not all in vitro models are suitable to study enzyme induction [ 48 , 49 ]; EROD activity does not measure only CYP1A1 activity [ 49 ]; and most of the compounds are not highly selective for CYP1A1 (see section of CYP1A1 inhibitors ). Moreover, enzyme inhibition effects by direct binding to the enzyme are more rapid and short than induction effects.…”