Alcohol and Smoking Mediated Oxidative Stress in Organ Toxicities: Role of Cytochrome P450 Systems

Alcohol consumption and tobacco smoking are the most common co-abused drugs in the world. They are not only deleterious by themselves to the health of individuals, but they also act synergistically in worsening several disease conditions. Numerous studies have shown that cancer of various organs such as liver and lungs, as well as many disease conditions such as cardiovascular and neurodegenerative involve both alcohol and smoking individually, and together they pose the major risk factors. Similarly, several recent reports have shown that alcohol and smoking are involved in worsening HIV-related conditions. Although some other minor pathways are involved in alcohol- and tobacco-mediated cancers and organ toxicities, cytochrome P450 (CYP) systems are the major pathways that induce reactive oxygen species and toxic metabolites leading to oxidative stress. For example, CYP2E1 is involved in alcohol-mediated oxidative stress leading to liver injury and cancers in many organs. Similarly, CYP2A6 is mainly involved in tobacco-mediated lung cancer, as well as toxicities in other organs including the brain. Therefore, in this review we have discussed the involvement of different isozymes of CYP in alcohol- and smoking-mediated oxidative stress and organ toxicities. In general, we cover 1) prevalence, disease, and life style among alcoholics and smokers, 2) general mechanisms of alcohol- and tobaccomediated oxidative stress, 3) The role of oxidative stress mediated toxicity in different disease states, and 4) clinical implications.