Title:Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1
Volume: 16
Issue: 6
Author(s): PSS Rao, Narasimha M. Midde, Duane D. Miller, Subhash Chauhan, Anil Kumar and Santosh Kumar
Affiliation:
Keywords:
Alcohol, cancer, CYP2E1, Diallyl sulfide.
Abstract: Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds
have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds
may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions
and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited.
DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics
including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and
reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown
that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated
toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality
for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate
DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances
in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic
drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing
novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme.
