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  • Title: Protective effects of diallyl sulfide, a garlic constituent, on the warm hepatic ischemia-reperfusion injury in a rat model.
    Author: Shaik IH, George JM, Thekkumkara TJ, Mehvar R.
    Journal: Pharm Res; 2008 Oct; 25(10):2231-42. PubMed ID: 18626753.
    Abstract:
    PURPOSE: The aim of this study is to evaluate the effects of diallyl sulfide (DAS) on the warm hepatic ischemia-reperfusion (IR) injury in a rat model. METHODS: Rats (n = 8-10/group) were subjected to sham operation or warm ischemia (1 h)-reperfusion (3 h) preceded by a single intraperitoneal dose (1.75 mmol/kg) of DAS or vehicle, and relevant biochemical parameters were monitored. RESULTS: Warm IR injury caused a significant increase in the plasma markers of liver injury, which was attenuated by DAS. The hepatoprotective effects of DAS were associated with significant reductions in lipid peroxidation markers and in situ generation of superoxide in the liver and increases in the glutathione levels of the liver and bile, suggestive of an antioxidant effect for DAS. Additionally, DAS caused an almost twofold increase in the protein expression of the liver heme oxygenase-1, an enzyme that confers cytoprotection against oxidative stress. Whereas the total cytochrome P450 remained unchanged, the protein levels and activity of CYP2E1, which plays an important role in the generation of reactive oxygen species, significantly decreased by DAS pretreatment. CONCLUSIONS: DAS protects the liver from warm IR injury by reducing oxidative stress through, at least in part, induction of heme oxygenase-1 and inhibition of CYP2E1.
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