Iminium Mechanism for Nicotine Toxicity and Addiction: Role of Oxidative
Stress and Electron Transfer
P. Kovacic and A. L. Cooksy
Department of Chemistry, San Diego State University,
San Diego CA 92182-1030
Abstract
The mechanism of nicotine toxicity is not completely delineated.
Considerable evidence points to involvement of oxidative stress,
reactive oxygen species, lipid peroxidation, DNA damage, and beneficial
effect of antioxidants. Previously, a suggestion was advanced for
participation of iminium metabolies which might operate, via electron
transfer with redox cycling, to produce radical entities. Support was
provided by reduction potentials which are in the range amenable to
electron transfer in Increasing evidence points to a role for
oxidative stress in toxicity by nicotine entailing major body organs.
The mechanism of addiction is also addressed. Possibilities for future
work based on the hypothetical approach include computational studies,
antioxidants, inhibition of oxidative enzymes, and inactivation of
toxic metabolites.