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Human & Experimental Toxicology, Vol. 27, No. 1, 55-63 (2008)
DOI: 10.1177/0960327108088978
© 2008 SAGE Publications

research-article

Regulation of oxidative stress–mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice

S Prasad

Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, India

N Kalra

Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, India

S Srivastava

Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, India

Y Shukla

Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, India

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�µg/mouse or 500�µg/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 (~30%) of antiapoptotic Bcl-2 and upregulation (~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.

Key Words: antioxidant enzymes • diallyl sulfide • DMBA • oxidative stress • Swiss albino mice


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