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Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice
1Department of Biological Science, Chosun University, Kwangju, South Korea. hgjeong@chosun.ac.kr
Abstract:
Diallyl sulfide (DAS), a flavor component of garlic that has been used as a food additive, exerts chemopreventive effects at several organ sites in rodents after administration of chemical carcinogens possibly by inhibiting carcinogen activation via cytochrome P450-mediated oxidative metabolism. In this study, we investigated the protective effect of DAS on the N-nitrosodimethylamine (NDMA)-induced immunosuppression of humoral and cellular responses in BALB/c mice and the possible mechanisms involved in this protection. We observed that oral administration of DAS prior to NDMA treatment for 14 consecutive days blocked the NDMA-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes, and the lymphoproliferative response to the T-cell and the B-cell mitogens in dose-dependent manners. Treatment of mice with DAS resulted in a significant decrease of cytochrome P450 2E1-dependent p-nitrophenol hydroxylase and NDMA demethylase activities. The results show that the protective effects of DAS against the NDMA-induced immunotoxicity may, at least in part, be due to its ability to block bioactivation of NDMA mainly by the inhibition of cytochrome P450 2E1.
Insights
Diallyl sulfide (DAS) protects against N-nitrosodimethylamine (NDMA)-induced immune suppression in mice. DAS inhibits NDMA bioactivation by blocking cytochrome P450 2E1 activity, preserving immune responses.
Area of Science:
- Toxicology
- Immunology
- Natural Products Chemistry
Background:
- Diallyl sulfide (DAS), a garlic component, shows chemopreventive effects.
- Chemical carcinogens like N-nitrosodimethylamine (NDMA) can suppress immune function.
- Cytochrome P450 enzymes mediate carcinogen activation and metabolism.
Purpose of the Study:
- To investigate the protective effect of DAS against NDMA-induced immunosuppression.
- To elucidate the mechanisms underlying DAS protection, focusing on cytochrome P450 2E1.
Main Methods:
- BALB/c mice were orally administered DAS prior to NDMA treatment for 14 days.
- Humoral immunity was assessed by antibody response to sheep erythrocytes.
- Cellular immunity was evaluated by lymphoproliferative responses to mitogens.
- Cytochrome P450 2E1 activity was measured using p-nitrophenol hydroxylase and NDMA demethylase assays.
Main Results:
- DAS administration blocked NDMA-induced suppression of antibody and lymphoproliferative responses in a dose-dependent manner.
- DAS treatment significantly decreased cytochrome P450 2E1-dependent enzyme activities.
- Inhibition of NDMA bioactivation by DAS was observed.
Conclusions:
- Diallyl sulfide protects against NDMA-induced immunotoxicity.
- The protective effect is partly attributed to DAS inhibiting cytochrome P450 2E1, thereby blocking NDMA bioactivation.