Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice

Jeong, Hye Gwang; Lee, Yong Woo

doi:10.1016/s0304-3835(98)00246-8

Cited by 42 publications

(15 citation statements)

References 28 publications

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“…At higher concentrations, the extracts had an inhibitory effect on T cell proliferation but lower concentrations of extracts resulted in an increase in T cell proliferation. Additionally, DAS treatment of BALB/c mice blocked the suppression of the antibody response caused by N-nitrosodimethylamine to T cell-dependent antigens, and the lymphoproliferative response to T cell and the B cell mitogens (92). …”

Section: Possible Mechanismsmentioning

confidence: 99%

Garlic and Onions: Their Cancer Prevention Properties

Nicastro

Ross

Milner

2015

Cancer Prevention Research

283

173

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The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiological studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biological processes that modify cancer risk. This review discusses the cancer preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps.

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Section: Possible Mechanismsmentioning

confidence: 99%

Garlic and Onions: Their Cancer Prevention Properties

Nicastro

Ross

Milner

2015

Cancer Prevention Research

283

173

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“…CYP2E1 inhibition, on the other hand, was found to be responsible for the protective effects of DAS against chemical-induced hepato- and immune-toxicities [51–53]. While exposure to various chemicals in these studies was associated with signs of liver damage, DAS treatment was observed to block the chemical induced-hepatotoxicity.…”

Section: Protective Effects Of Dasmentioning

confidence: 99%

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Rao¹,

Midde²,

Miller³

et al. 2015

CDM

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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.

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“…In addition, knocking down CYP2E1 expression through CYP2E1 siRNA almost completely abolished ethanol-induced caspase-3 cleavage (Figure 1c). Furthermore, diallyl sulfide (DAS), a selective chemical inhibitor of CYP2E1, which is also a food additive and has protective effect on immune cells, 16 abolished ethanol-induced apoptosis (Figure 1d). In addition, 100 mM vitamin C, as well as vitamin E, blocked the effect of ethanol on induction of caspase-3 cleavage activity (Figures 1e and f), suggesting that ethanol-induced apoptosis is mediated through ROS production.…”

Section: Resultsmentioning

confidence: 99%

“…Similar to TUNEL assay, DAS alone caused B15% cell death compared with control. Although DAS has a protective effect, 16 it is also known to cause toxicity at high concentration and when used for longer time. 17 Therefore, we performed a subsequent experiment using CYP2E1 siRNA to assess the specificity of DAS.…”

Section: Resultsmentioning

confidence: 99%

Regulation of Cytochrome P450 2E1 expression by ethanol: Role of oxidative stressmediated PKC/JNK/SP1 pathway

2013

J Bioequiv Availab

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CYP2E1 metabolizes ethanol leading to production of reactive oxygen species (ROS) and acetaldehyde, which are known to cause not only liver damage but also toxicity to other organs. However, the signaling pathways involved in CYP2E1 regulation by ethanol are not clear, especially in extra-hepatic cells. This study was designed to examine the role of CYP2E1 in ethanolmediated oxidative stress and cytotoxicity, as well as signaling pathways by which ethanol regulates CYP2E1 in extra-hepatic cells. In this study, we used astrocytic and monocytic cell lines, because they are important cells in central nervous system . Our results showed that 100 mM ethanol significantly induced oxidative stress, apoptosis, and cell death at 24 h in the SVGA astrocytic cell line, which was rescued by a CYP2E1 selective inhibitor, diallyl sulfide (DAS), CYP2E1 siRNA, and antioxidants (vitamins C and E). Further, we showed that DAS and vitamin C abrogated ethanol-mediated (50 mM) induction of CYP2E1 at 6 h, as well as production of ROS at 2 h, suggesting the role of oxidative stress in ethanol-mediated induction of CYP2E1. We then investigated the role of the protein kinase C/c-Jun N-terminal kinase/specificity protein1 (PKC/JNK/SP1) pathway in oxidative stress-mediated CYP2E1 induction. Our results showed that staurosporine, a non-specific inhibitor of PKC, as well as specific PKCf inhibitor and PKCf siRNA, abolished ethanol-induced CYP2E1 expression. In addition, inhibitors of JNK (SP600125) and SP1 (mithramycin A) completely abrogated induction of CYP2E1 by ethanol in SVGA astrocytes. Subsequently, we showed that CYP2E1 is also responsible for ethanol-mediated oxidative stress and apoptotic cell death in U937 monocytic cell lines. Finally, our results showed that PKC/JNK/SP1 pathway is also involved in regulation of CYP2E1 in U937 cells. This study has clinical implications with respect to alcohol-associated neuroinflammatory toxicity among alcohol users. 1 To a lesser extent, they are also involved in xenobiotic metabolism in other organs, such as intestine, brain, and kidney. CYP2E1 is known to metabolize ethanol in the liver, especially in chronic alcohol users; 2 however, the persistent use of alcohol and resulting alcohol metabolism is known to cause liver toxicity. 3The alcohol metabolism-mediated liver toxicity occurs through the formation of reactive oxygen species (ROS) and the reactive metabolite, acetaldehyde, which ultimately cause DNA damage and lipid and protein oxidations. 4 Low levels of alcohol in occasional or social mild-tomoderate drinkers are metabolized mainly by alcohol dehydrogenase (ADH), which also appears to cause oxidative stress-mediated liver toxicity.5 However, alcohol-inducible CYP2E1 also has an important role in alcohol metabolism and mediate liver impairment among variety of alcohol drinkers. 2Although the role of CYP2E1 in alcohol-mediated liver toxicity is well known, similar studies are limited in extra-hepatic cells, especially cells from the CNS. Results from previous studies have led to the s...

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Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice

Cited by 42 publications

References 28 publications

Garlic and Onions: Their Cancer Prevention Properties

Garlic and Onions: Their Cancer Prevention Properties

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Regulation of Cytochrome P450 2E1 expression by ethanol: Role of oxidative stressmediated PKC/JNK/SP1 pathway

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