Citation

Yang CS, Chhabra SK, Hong JY, Smith TJ. J. Nutr. 2001; 131(3s): 1041S-5S.

Copyright

(Copyright © 2001, American Society of Nutritional Sciences)

DOI

10.1093/jn/131.3.1041S

PMID

11238812

Abstract

Diallyl sulfide (DAS) is a flavor compound derived from garlic and is sequentially converted to diallyl sulfoxide (DASO) and diallyl sulfone (DASO(2)) by cytochrome P(450) 2E1 (CYP2E1). These compounds have been shown to reduce the incidence of a multitude of chemically induced tumors in animal models. The impediment of phase I activation of these carcinogens is hypothesized to be accountable for the reduction in tumor incidence. Indeed, DAS, DASO and DASO(2) are competitive inhibitors of CYP2E1. DASO(2), in addition, is a suicide inhibitor of CYP2E1. These compounds have been shown to reduce carbon tetrachloride-, N-nitrosodimethylamine- and acetaminophen-induced toxicity in rodents. All three chemicals are substrates for CYP2E1. The protective effect was observed when the organosulfur compounds were given before, during or soon after chemical treatment. DAS and DASO(2) inhibited the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related lung tumorigenesis in A/J mice. Because CYP2E1 does not play a key role in NNK activation, the inhibition of other CYP enzymes active in NNK metabolism is likely. DAS also has been shown to induce other CYP and phase II enzymes as well as decrease hepatic catalase activity. All of these effects are observed at concentrations much higher than what is normally ingested by humans. The biological activities of garlic and its related compounds at lower concentrations that mimic human consumption remain to be studied further.

Language: en

Keywords

Allyl Compounds; Animals; Anticarcinogenic Agents; Carcinogens; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP2E1 Inhibitors; Enzyme Activation; Enzyme Induction; Enzyme Inhibitors; Garlic; Glutathione Transferase; Incidence; Liver; Lung Neoplasms; Nitrosamines; Plants, Medicinal; Rodentia; Sulfides; Sulfones; Sulfoxides