Allicin up-regulates cellular glutathione level in vascular endothelial cells.
BACKGROUND
Allicin in garlic is the primary active compound known to rapidly interact with free thiols.


OBJECTIVE
To examine the effect of allicin on gene expression and glutathione cellular level in vascular endothelial cells.


METHODS
Cultured endothelial cells were exposed to allicin; mRNA was prepared and subjected to Micro-array and Real-Time PCR. Glutathione cellular level was determined on cell lysates.


RESULTS
Micro-array analysis demonstrated allicin-induced up- and down-regulation of 116 and 100 genes, respectively. Up-regulated genes included the phase II detoxifying enzymes thioredoxin reductase 1 and 2, heme oxygenase-1 and glutamate cysteine lygaze modifier subunit, the rate limiting enzyme in glutathione biosynthesis. Endothelial cells exposed to allicin and its derivatives containing glutathione or cysteine residues increased cellular glutathione. Allicin increased the glutathione level in a concentration and time-dependent manner up to 8-fold at a concentration of 10-20 microM after 28 h exposure. Furthermore, allicin derivative-treated cultures demonstrated a 50% decrease in tBuOOH cytotoxicity.


CONCLUSIONS
These results may suggest a putative role for allicin and its derivatives in preventing reactive oxygen species damage by up-regulating the phase II detoxifying enzymes and increasing the cellular glutathione level.
Horev-Azaria
Limor
L
Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Eliav
Shlomit
S
Izigov
Nira
N
Pri-Chen
Sarah
S
Mirelman
David
D
Miron
Talia
T
Rabinkov
Aharon
A
Wilchek
Meir
M
Jacob-Hirsch
Jasmine
J
Amariglio
Ninette
N
Savion
Naphtali
N
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004220:Disulfides; D042783:Endothelial Cells / Q000737:chemistry* / Q000201:enzymology; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013441:Sulfinic Acids / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics; D014471:Umbilical Veins; D015854:Up-Regulation / Q000187:drug effects*
D000975:Antioxidants; D004220:Disulfides; D012333:RNA, Messenger; C086300:S-allylmercaptocysteine; D013441:Sulfinic Acids; C006452:allicin; D051547:Heme Oxygenase-1; D013880:Thioredoxin-Disulfide Reductase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003545:Cysteine