Protection of garlic against carcinogen genotoxicity
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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
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


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.


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)


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


SAC

DADS

DADSO

AM

()

H2O2

MMS

()

()

4-NQO

RESULTS

Co-treatment studies

 : inhibition of the genotoxicity

() : slight inhibition

() :slight increase

- : no effect


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


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


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  »


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)


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)


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)


Wp 6 cancer general conclusion
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


Wp 6 cancer deliverables
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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