Abstract
S-Allyl-l-cysteine sulfoxide (ACSO) is a precursor of garlic-odor compounds like diallyl disulfide (DADS) and diallyl trisulfide (DATS) known as bioactive components. ACSO has suitable properties as a food material because it is water-soluble, odorless, tasteless and rich in bulbs of fresh garlic. The present study was conducted to examine the preventive effect of ACSO on hepatic injury induced by CCl4 in rats. ACSO, its analogs and garlic-odor compounds were each orally administered via gavage for five consecutive days before inducing hepatic injury. Then, biomarkers for hepatic injury and antioxidative state were measured. Furthermore, we evaluated the absorption and metabolism of ACSO in the small intestine of rats and NF-E2-related factor 2 (Nrf2) nuclear translocation by ACSO using HepG2 cells. As a result, ACSO, DADS and DATS significantly suppressed the increases in biomarkers for hepatic injury such as the activities of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH), and decreases in antioxidative potency such as glutathione (GSH) level and the activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx). We also found ACSO was absorbed into the portal vein from the small intestine but partially metabolized to DADS probably in the small intestine. In in vitro study, ACSO induced Nrf2 nuclear translocation in HepG2 cells, which is recognized as an initial trigger to induce antioxidative and detoxifying enzymes. Taken together, orally administered ACSO probably reached the liver and induced antioxidative and detoxifying enzymes by Nrf2 nuclear translocation, resulting in prevention of hepatic injury. DADS produced by the metabolism of ACSO in the small intestine might also have contributed to the prevention of hepatic injury. These results suggest potential use of ACSO in functional foods that prevent hepatic injury and other diseases caused by reactive oxygen species (ROS).
Highlights
Sulfur is one of the key elements involved in the regulation of biological functions in the human body
aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) activities were increased following injection of CCl4 in the control groups, and these increases were significantly suppressed by oral administration of Allyl-l-cysteine sulfoxide (ACSO), ACS, diallyl disulfide (DADS), and diallyl trisulfide (DATS) (p < 0.01)
thiobarbituric acid reactive substances (TBARS) was increased by the injection of CCl4 in the control groups, while oral administration of ACSO, ACS, DADS and DATS significantly suppressed the increase in TBARS after the injection of CCl4 (p < 0.01)
Summary
Sulfur is one of the key elements involved in the regulation of biological functions in the human body. Pivotal roles of organosulfur compounds are to maintain redox balance and to detoxify toxic agents. Reduced glutathione (GSH) is ubiquitously expressed in cells and reduces oxidative agents, such as hydroxyl radicals, oxide anion radicals, and hydrogen peroxide [1,2], playing a central role in detoxification [3,4]. GSH is important for such defense, oral intake of GSH does not necessarily increase these antioxidative and detoxifying activities in the human body [5,6]. Administered GSH can be delivered to various organs of the human body [7]; the effects of GSH are cancelled by the metabolite l-cysteine-l-glycine (Cys-Gly), which serves as a pro-oxidant. In order to reduce oxidative stress via oral administration of a natural compound, it is not to reduce oxidative stress via oralthe administration a natural compound, not sufficient forina order functional compound to merely reach target organ.ofThe compound needs ittoisincrease sufficient for a functional compound to merely reach the target organ
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