Regulation of oxidative stress-mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice.
Diallyl sulfide, a sulfur-containing volatile compound present in garlic (Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, apoptosis-inhibiting effects of diallyl sulfide against a carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethyl benz(a)anthracene (DMBA), in Swiss albino mice were observed. The animals were given either 250 microg/mouse or 500 mug/mouse of diallyl sulfide for 1 week after a single intragastric dose of 7,12-dimethyl benz(a)anthracene (50 mg/kg body weight). Results showed that diallyl sulfide supplementation effectively protects against 7,12-dimethyl benz(a)anthracene-induced oxidative stress, characterized by restored antioxidant enzyme levels (up to 64%) and lipid peroxidation (up to 25%). Flow cytometric analysis showed a reduction in apoptotic cell population in hypodiploid region in diallyl sulfide-supplemented animals. Inhibition of apoptosis was preceded by decrease in reactive oxygen species levels and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In 7,12-dimethyl benz(a)anthracene-exposed animals, downregulation approximately 30%) of antiapoptotic Bcl-2 and upregulation (approximately 60%) of pro-apoptotic Bax proteins were observed. These alterations were restored significantly by diallyl sulfide supplementation, indicating inhibition of apoptosis. Thus, these results show that diallyl sulfide provides protection against oxidative damage induced by 7,12-dimethyl benz(a)anthracene in mouse liver and may be an effective chemopreventive and therapeutic agent by modulating expression of cell-growth regulatory proteins.
Prasad
S
S
Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, India.
Kalra
N
N
Srivastava
S
S
Shukla
Y
Y
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D019254:Genes, bcl-2; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species; D013440:Sulfides / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics
D000498:Allyl Compounds; D002273:Carcinogens; D017382:Reactive Oxygen Species; D013440:Sulfides; D017392:Thiobarbituric Acid Reactive Substances; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene; C038491:allyl sulfide