Cigarette smoke containing either high or low levels of nicotine during adolescence differentially affects novelty seeking and anxiety-like behaviors of mice

Abstract

s / Toxicology Letters 229S (2014) S40–S252 S89 (BITC), 4,5-epithiopentylnitrile (4,5ETN), 3-butenylnitrile (BN) and pent-4-enylnitrile (PN) to treat MCL-5 cells and measured reactive oxygen species production, reduced glutathione levels and CYP1A activity (ethoxyresofufin O-deethylase activity). The isothiocyanates induced ROS and depleted glutathione levels, whereas the epithionitriles only marginally induced ROS and had little effect on glutathione; the nitriles failed to induce ROS or affect glutathione. The isothiocyanates AITC and BITC inhibited CYP1A activity in a dose-dependent manner, whereas the epithionitriles and nitriles 3,4-ETN, 3BTN, 4,5ETN and 4PTN did not. Our data suggest that the lipophilic arylalkyl ITC exert their toxicity by binding to the CYP active site leading to competitive inhibition and enzyme uncoupling, which in turn promotes ROS production and depletion of GSH. http://dx.doi.org/10.1016/j.toxlet.2014.06.848 P3: Juvenile toxicology