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Protection of garlic against carcinogen genotoxicity

Protection of garlic against carcinogen genotoxicity. Anne-Marie Le Bon , Christine Belloir, Varsha Singh. Milestones :.  In vitro evaluation of the antigenotoxic properties of garlic compounds in HepG2 cells

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Protection of garlic against carcinogen genotoxicity

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  1. Protection of garlic against carcinogen genotoxicity Anne-Marie Le Bon , Christine Belloir, Varsha Singh Milestones :  In vitro evaluation of the antigenotoxic properties of garlic compounds in HepG2 cells  Evaluation of the antigenotoxic properties of garlic extracts in tissues of rat

  2. The studied molecules were : DADS (diallyl sulfide) DADSO (allicin) SAC (S-allyl cystein) AM (allyl mercaptan) Range : 5 to 100 µM Genotoxic compound Broken DNA = comet Undamaged DNA In vitro evaluation of antigenotoxic properties of garlic compounds in HepG2 cells Objectives : to assess if garlic compounds prevent DNA alterations induced by mutagenic compounds in a human cell line, HepG2 cells. DNA alterations were measured using the comet test.

  3. Garlic compound +mutagen PROTOCOLS  Pre-treatment studies : cells are treated firstwith the garlic compound and then with the pro-mutagen Garlic compound Pro-mutagen Hypothesis : inhibition or induction of xenobiotic metabolizing enzymes Mutagens : benzopyrene (BaP) aflatoxin B1 (AFB1) nitrosodimethylamine (NDMA) P450 1A P450 1A, 3A P450 2E1  Co-treatment studies : cells are treated with both the garlic compound and the direct-acting mutagen at the same time Hypothesis : scavenging of mutagenic compounds Mutagens : hydrogen peroxide (H2O2) methyl methane sulfonate (MMS) 4-nitrosoquinoline oxide (4-NQO)

  4. DADS DADSO AM SAC   BaP  ()  AFB1 n.d. n.d. n.d. n.d. NDMA RESULTS Pre-treatment studies  : inhibition of the genotoxicity () : slight inhibition - : no effect n.d. : not determined

  5. SAC DADS DADSO AM  ()   H2O2    MMS ()  () 4-NQO RESULTS Co-treatment studies  : inhibition of the genotoxicity () : slight inhibition () :slight increase - : no effect

  6. 120 100 80 % of DNA alterations 60 40 20 0 H202 5 µM 25 µM 50 µM 100µM RESULTS Effects of S-allylcystein on H2O2 genotoxicity in HepG2 cells

  7. CONCLUSIONS  Garlic sulfur compounds prevent genotoxicity induced by direct- and indirect-acting compounds  DADS and AM can act throught both mechanisms : modulation of EMX and scavenging DADS is more efficient than AM  DADS and SAC act rather by scavenging genotoxic compounds  The metabolites of DADS, DADSO and AM, could be the effective compounds in vivo

  8. In vivo evaluation of antigenotoxic properties of garlic extracts in rats Objectives : to assess if garlic ingestion prevent DNA alterations induced by genotoxic compounds in rat liver Studied material : Garlic powder «  0 kg/ha SO4 » Garlic powder «  100 kg/ha SO4  » Garlic powder «  200 kg/ha SO4  »

  9. 5 6 7 4 5 %garlic powder PROTOCOL intraperitoneal injection of a genotoxic agent : AFB1 NDMA (4 hours before sacrifice) 60 Wistar male rats weeks Sacrifice Group C : control diet SA : Garlic 0 kg/ha SO4 SB : Garlic 100 kg/ha SC : Garlic 200 kg/ha Liver DNA damage evaluation (comet test)

  10. 7 6 5 * 4 * DNA damage (OTM) * 3 2 1 0 C SA SB SC C SA SB SC C SA SB SC + NDMA + AFB1 (control) RESULTS Effects of garlic ingestion on DNA damage in rat liver (5 rats / group) *: significantly different from the group C (Dunnett ’s test, p < 0.05)

  11. CONCLUSIONS  Garlic powders are not genotoxic by themselves.  Garlic powder ingestion reduce liver DNA damage induced by AFB1. No statistical difference was observed between fertilisation levels. Mechanims of action : induction of CYP 1A and/or GST ?  A slight reduction of NDMA genotoxicity was observed but this effect was not significant. Mechanims of action : inhibition of CYP 2E1 ?  To be done shortly : colon study (preliminary studies in progress)

  12. WP 6 Cancer : General conclusion Metabolism of DADS almost elucidated, proposition of a scheme of the metabolic pathway.  In vivo after garlic powder administration to rats, we observed a modulation of hepatic enzymes involved in carcinogen activation or detoxication. Sulfur compounds prevent the genotoxicity of carcinogens in a human cell-line. They act by scavenging ultimate metabolites and/or by modulating the activity of carcinogen metabolizing enzymes

  13. WP 6 Cancer : Deliverables DH. 8:In vitro metabolism of diallyl disulfide, ajoene and allicin (P12) : done, publication in progress DH. 9: In vitro effects of sulphur compounds on human P450 iso-enzymes (P12) : done DH. 10: In vitro evaluation of the anti-genotoxic properties of garlic compounds in HepG2 cells (P12) : done DH.13: In vivo metabolism of diallyl disulfide (P12) : done, publication submitted DH. 14: Effects of garlic extracts on carcinogen-metabolising enzymes (P12) : done, publication in progress DH. 15: In vivo evaluation of the antigenotoxic properties of garlic extracts in rats (P12) : in progress

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