Water-soluble Organosulfur Compounds Research Articles

Sensitive and accurate determination of oil-soluble and water-soluble organosulfur compounds in garlic matrix using reversed phase-high performance liquid chromatography.

Garlic is in the family Liliaceae and has many different constituents such as organic sulfur compounds, amino acids, carbohydrates, minerals, and vitamins. In this work, a simple, sensitive, and accurate analytical method was developed for the determination of selected organosulfur compounds (OSCs) in garlic bulbs using reversed phase-high performance liquid chromatography (RP-HPLC). Oil-soluble and water-soluble OSCs were extracted from the garlic samples via acetonitrile and deionized water, respectively. The OSCs were separated on a Phenomenex C18 (250 mm, 4 mm, 5mm) column and the monitoring was performed with a UV detector at 220 nm. An isocratic mobile phase comprising of 0.10 M trifluoroacetic acid (TFA) in 85% acetonitrile (ACN) and 0.10 M TFA in distilled water (DW) (90: 10% v/v) was used to elute the analytes. Under optimum experimental conditions, the limits of detection (LOD) for the analytes were calculated in the range of 0.09 to 0.17 mg/kg. For the garlic sample extracts analyzed under optimal instrumental conditions, DAS (diallyl sulfide), DADS (diallyl disulfide), and DATS (diallyl trisulfide) were detected in the ranges of 8.0 to 32.5 mg/kg, 20.4 to 67.3 mg/kg, and 60.7 to 356.6 mg/kg, respectively. Spiked recovery experiments were conducted on the garlic samples to confirm the method's applicability and accuracy. The recovery results ranged between 39.0% and 90.9% for the garlic samples extracted with deionized water. The developed method is simple, precise, accurate, reliable, and time-effective for the determination of OSCs. Additionally, the green profile of the developed method was investigated by using AGREEprep software and the greenness score was recorded as 0.65, indicating that the method developed is environmentally friendly.

Molecular Docking Studies with Garlic Phytochemical Constituents to Inhibit the Human EGFR Protein for Lung Cancer Therapy

In both developed and emerging economies, carcinoma is one of the most frequent malignancies. Non-small cell lung cancer accounts for 80% of all melanoma within India. The basic concept of molecular precision medicine for lung cancer is the EGFR (Epidermal growth factor receptor), which belongs to the tyrosine kinase receptor family (RTKs). Garlic (Allium sativum L), an Indian Traditional spice from the Allium family, appears to be capable of inhibiting cancer cell formation through an apoptotic route. In the present research, the competence and binding ability of various phytochemical compounds from garlic targeting lung melanoma marker protein were assessed. Garlic's medicinal benefits are assumed to be due to key components within the elemental composition, such as organosulfur compounds and flavonoids. There were 19 compounds along with 2 reference compounds that were used for molecular docking purposes. The study revealed that the chemicals investigated are bound effectively to EGFR. When compared to water-soluble and lipid-soluble organosulfur compounds, garlic flavonoids had the anticipated free energy of interaction. Especially in contrast to Alliin, S-Methyl-L-cysteine, Kaempferol, Quercetin, Myrecetin, Apigenin along with Erlotinib demonstrated excellent interaction. Alliin, the much more prevalent component throughout the whole garlic bulb, has a stronger affinity via intermolecular hydrogen bonding, with a binding energy of -7.4 kcal/ Mol. The water-soluble chemical S-Methyl-L-cysteine also had positive interactions with EGFR (-7.3 Kcal/mol). Among the flavonoid groups studied, Quercetin, Myrecetin and Apigenin were found to be the best suitable compound with a binding energy of -8.5 kcal/ Mol. The current findings pave the way for a deeper understanding of garlic's active substance interactions with EGFR. The substances discovered might be utilised as a prototype for anti-cancer treatmentHowever, more research into these compounds' biochemical functions is required before they can be used to treat lung cancer.

Potential Anticancer Effects of Aged Garlic Extract and its Water-soluble Organosulfur Compounds

Background: Cancer is among the leading causes of morbidity and mortality globally; it often leads to a steep rise in healthcare expenses. It is a known fact that various dietary ingredients such as aged garlic is an active anticancer agent, and its extracts do not have a strong odor and pungent taste.
 Purpose: This review summarizes the potential beneficial effects of aged garlic extract (AGE) and its water-soluble organosulfur compounds on the cancer incidences, and in the prevention and improvement of malignancy factors.
 Methods: The study utilizes systematic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar and Cochrane. The study utilizes secondary information based on the studies conducted in cancer cell lines, animal and humans as there are increasing evidence of the efficacy of AGE and AGE-derived water-soluble organosulfur compounds in cancer and other malignancies.
 Conclusion and Recommendation: Although animal and laboratory results were mostly consistent, there is variable evidence from human studies. The overall findings suggest that consumption of AGE and AGE-derived organosulfur compounds can offer significant protection against cancer. In our review, we found that there are shortcomings in various studies. Therefore, we recommend that more investigations are necessary to establish whether aged garlic extract could be considered for cancer prevention.

High doses of S-methylcysteine cause hypoxia-induced cardiomyocyte apoptosis accompanied by engulfment of mitochondaria by nucleus

Despite its important role as a medicinal plant, some studies reported a toxic effect for garlic (Allium sativum) when given in higher doses. Herein, we investigated the possible cardiotoxic effects of high doses of S-methylcysteine (SMC), a water soluble organosulfur compound present in garlic. Rats were orally administered SMC at a low dose (50mg), high dose (150mg) and very high dose (300mg)/kg body weight, or saline (control) for 10days. High and very high doses of SMC resulted in a significant increase in serum cardiac injury biomarkers [aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac troponin T (cTnT)], as well as oxidative stress marker nitric oxide (NO) concentration in heart and a significant decrease in cardiac superoxide dismutase (SOD) activity. Moreover, ultrastructure findings in myocardium of rats treated by high and very high doses showed inter-bundle vacuolation, loss of myofibrils, and centripetal movement of mitochondria towards nucleus. The mitochondria were partially surrounded by nuclear membrane at high dose SMC, and completely engulfed by nucleus at very high dose. This centripetal movement of mitochondria accompanied by cardiomyocytes hypoxia-induced apoptosis as evident by increasing TUNEL positive cells as well as upregulation of apoptotic genes (caspase3 and Bax), hypoxia inducible factor 1 alpha (HIF1α), dynein light chain 1 (DYNLL1) and downregulation of the anti-apoptotic marker, Bcl2. We conclude that high and very high doses of SMC cause hypoxia induced cardiomyocyte apoptosis accompanied by engulfment of mitochondria by nucleus.

Factors limiting sulfolane biodegradation in contaminated subarctic aquifer substrate.

Sulfolane, a water-soluble organosulfur compound, is used industrially worldwide and is associated with one of the largest contaminated groundwater plumes in the state of Alaska. Despite being widely used, little is understood about the degradation of sulfolane in the environment, especially in cold regions. We conducted aerobic and anaerobic microcosm studies to assess the biological and abiotic sulfolane degradation potential of contaminated subarctic aquifer groundwater and sediment from Interior Alaska. We also investigated the impacts of nutrient limitations and hydrocarbon co-contamination on sulfolane degradation. We found that sulfolane underwent biodegradation aerobically but not anaerobically under nitrate, sulfate, or iron-reducing conditions. No abiotic degradation activity was detectable under either oxic or anoxic conditions. Nutrient addition stimulated sulfolane biodegradation in sediment slurries at high sulfolane concentrations (100 mg L-1), but not at low sulfolane concentrations (500 μg L-1), and nutrient amendments were necessary to stimulate sulfolane biodegradation in incubations containing groundwater only. Hydrocarbon co-contamination retarded aerobic sulfolane biodegradation rates by ~30%. Our study is the first to investigate the sulfolane biodegradation potential of subarctic aquifer substrate and identifies several important factors limiting biodegradation rates. We concluded that oxygen is an important factor limiting natural attenuation of this sulfolane plume, and that nutrient amendments are unlikely to accelerate biodegradation within in the plume, although they may biostimulate degradation in ex situ groundwater treatment applications. Future work should be directed at elucidating the identity of indigenous sulfolane-degrading microorganisms and determining their distribution and potential activity in the environment.

S-allylcysteine의 항암효과

S-allylcysteine (SAC) is an aged garlic derived water soluble organosulfur compound and has been suggested to have anticarcinogenic activity against diverse types of cancer cells. This review summa-rizes the cellular signaling pathways and molecular mechanisms whereby SAC exerts its effects on cel-lular proliferation, apoptosis, cell cycle progression and metastasis based on the results from both in vitro and in vivo studies. SAC activates proapoptotic proteins including Bax and caspase-3, but sup-presses antiapoptotic Bcl-2 family proteins to bring about cancer cell death through mitochon-dria-mediated intrinsic pathway. SAC also inhibits cellular proliferation by inducing cell cycle arrest in which SAC reduces expression and activation of NF-

Chemoprevention of Rat Carcinogenesis by Water-soluble Organosulfur Compounds

Chemoprevention of Rat Carcinogenesis by Water-soluble Organosulfur Compounds

Role of garlic in the prevention of ischemia‐reperfusion injury

Garlic in different forms has antioxidant properties. These properties are shown to be due to the existence of compounds such as water soluble organosulfur compounds, S-allylcysteine and lipid soluble compounds like diallyl sulfide. The in vivo and in vitro ischemia reperfusion studies showed that prophylactic administration of aqueous garlic prior to ischemia reperfusion inhibit lipid peroxidation and prevent depletion in glutathione through its compounds that led to functional recovery. Its ability to inhibit neutrophil migration could suppress fibrosis formation. These preventive effects are seen in models that studied organs such as kidney and liver with functional recovery. Organ system specific activity such as angiotensin converting enzyme-inhibiting activity contributes to a cardioprotective and blood pressure lowering effect. Future studies should focus on post ischemia reperfusion administration of garlic to explore its rescue potential rather than prophylactic impact. Bench research findings should be translated into clinical use through human studies.

Dual-Pathway Kinetics Assessment of Sulfur Poisoning of the Hydrogen Oxidation Reaction at High-Surface-Area Platinum/Vulcan Carbon Electrodes

Hydrogen oxidation reaction (HOR) kinetics were measured at films of high-surface-area platinum/Vulcan carbon (Pt/VC) exposed to aqueous solutions of mercaptopropionic acid (MPA), a water-soluble organosulfur compound, using rotating disk voltammetry. Results were fitted to a recently developed dual-pathway kinetics model. At all levels of sulfur coverage (0-96% of a monolayer of MPA), the potential-independent Tafel-Volmer pathway, or two-site HOR pathway, seems largely unaffected. Decreases in current at low overpotentials are accounted for entirely by loss in surface area of the electrode due to site occlusion by the adsorbed organosulfur. Rates for the single site, potential-dependent Heyrovsky-Volmer pathway decrease by a factor of 10 after the initial MPA exposure (50% of a monolayer), indicating an electronic effect of sulfur on the potential-dependent Heyrovsky reaction.

Neurocognitive effect of dietary S‐allyl‐L‐cysteine in patients with mild cognitive impairment (MCI)

S-allylcysteine (SAC), one of the water-soluble organosulfur compounds with thioallyl group found in garlic, was shown to have neuroprotective effects in several in vitro and in vivo studies. Furthermore, SAC ameliorates learning deficits in senescence-accelerated mice. We administered SAC to patients with mild cognitive impairment (MCI). Diagnoses for MCI were established based on neuropsychological testing according to the criteria of Korean version of Consortium to Establish a Registry for Alzheimer¡¯s Disease neuropsychological test battery (CERAD-K). The cognitive functions were assessed by trail making test, visual span test, word color test, and visual continuous performance test (visual CPT). The scores for visual span test and CPT, which are known to measure continuous attention and working memory, were significantly improved after SAC supplementation. The visual CPT scores, known to measure working memory capacity, showed a significant inverse correlation with the Wechsler delayed memory test scores, while the differences in commission error t-score (CETC) and commission error percentile (CEPC) were positively correlated with the Wechsler delayed recall test scores. These results suggest a potential of S-allylcysteine extracted from garlic as a promising dietary supplement for the improvement of cognitive function in patients with mild cognitive impairment.

Antiproliferative effect of diallyl disulfide (DADS) on prostate cancer cell line LNCaP

Garlic has been used throughout the world to treat coughs, toothache, earache, dandruff, hypertension, hysteria, diarrhoea, dysentery, diptheria, vaginitis and many other conditions. Garlic contains a complex mixture of oil and water-soluble organosulfur compounds. Diallyl disulfide (DADS), an oil-soluble constituent of garlic seems to be effective in reducing tumour cells originating from colon, lung and skin. Hence our present study focuses on the dose-dependent effect of DADS on an androgen-dependent prostate cancer cell line. Various concentrations of DADS ranging from 25 to 100 microM were given to LNCaP cells and the activity of lactate dehydrogenase (LDH) prostatic acid phosphatase (PAcP) and the level of prostate specific antigen were studied. DADS reduced the secretory activity of LNCaP cells with the gradual increase in dosage. DADS was found to act as a good antiproliferative agent, which was confirmed by proliferation assay. DADS also induced apoptosis and nuclear segmentation in the higher doses.

N -acetylcysteine and S -methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage

N-acetylcysteine (NAC) and S-methylcysteine (SMC), water soluble organosulfur compounds contained in garlic, were evaluated for chemoprevention of hepatocarcinogenesis after 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) initiation in rats. Intergastric treatment with NAC or SMC five times a week resulted in decreased numbers and areas of preneoplastic, glutathione S-transferase placental form (GST-P) positive foci of the liver in a dose-dependent manner. Moreover, cell proliferation was reduced in GST-P positive foci by NAC and SMC. Insulin-like growth factor I (IGF-I) and inducible nitric oxide synthase (iNOS) mRNA expressions were found downregulated in the liver by NAC. The studies indicate that NAC can serve as a chemopreventive agent for rat hepatocarcinogenesis induced by MeIQx by reducing cell proliferation, which may involve IGF-I and iNOS downregulation.

Revised rat multi-organ carcinogenesis bioassay for whole-body detection of chemopreventive agents: modifying potential of S-methylcysteine

The DMBDD rat multi-organ carcinogenesis model based on two-stage carcinogenesis theory was revised to make more suitable assay system for detecting chemopreventive effects of chemical substances by increasing the doses of two carcinogens, 1,2-dimethylhydrazine dihydrochloride (DMH) and N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN). The revised bioassay resulted in increasing preneoplastic or neoplastic lesions in the colon, urinary bladder and liver. S-Methylcysteine (SMC), a water-soluble organosulfur compound, was used as a test chemical in the new initiation regimen. Though SMC did not express clear-cut inhibitory effects in tumor levels, it showed modifying effects on the development of lung hyperplastic and colon preneoplastic lesions. In conclusion, the present model featuring high yields of preneoplastic and neoplastic lesions with low mortality in a short period (30 weeks), might be suitable for testing the efficacy of possible chemopreventive chemicals at the whole-body level.

S-Alk(en)yl Cysteines of Garlic Inhibit Cholesterol Synthesis by Deactivating HMG-CoA Reductase in Cultured Rat Hepatocytes

The effects of water-soluble organosulfur compounds of garlic on hepatic cholesterol biosynthesis in cultured rat hepatocytes were studied. S-Alk(en)yl cysteines, i.e., S-allyl cysteine (SAC), S-ethyl cysteine (SEC) and S-propyl cysteine (SPC) inhibited cholesterol synthesis from [(14)C]acetate but not from [(14)C]mevalonate. The activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in the cells treated with SAC, SEC and SPC was 30-40% lower than that of the untreated cells. S-Alk(en)yl cysteines did not alter abundance of mRNA coded for HMG-CoA reductase or protein concentration of the enzyme. The ratio of expressed to total activity (E/T) of HMG-CoA reductase was then determined as an index of phosphorylation status of the enzyme. The E/T ratio was reduced 18-29% by SAC, SEC and SPC, resulting primarily from decreased expressed activity. The results suggest that S-alk(en)yl cysteines inhibit cholesterol synthesis by deactivating HMG-CoA reductase via enhanced phosphorylation, but not changing levels of mRNA or the amount of the enzyme. Additionally, of the three S-alk(en)yl cysteines tested, only SAC appears to further decrease the activity of HMG-CoA reductase by increasing sulfhydryl oxidation of the enzyme.

Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice

S-allylmercaptocysteine is one of the water-soluble organosulfur compounds in ethanol extracts of garlic ( Allium sativum L.). We had demonstrated earlier that treatment with S-allylmercaptocysteine before acetaminophen administration protects mice against acetaminophen-induced hepatotoxicity. In this study, we examined the therapeutic effect of S-allylmercaptocysteine treatment after acetaminophen administration. A single dose of S-allylmercaptocysteine (200 mg/kg, p.o.) to mice 0.5 h after acetaminophen administration (500 mg/kg, p.o.) significantly suppressed both the increase in plasma alanine aminotransferase activity and the hepatic necrosis, and also reduced acetaminophen-induced mortality from 43% to 0%. These data indicate that S-allylmercaptocysteine is useful as an antidote for acetaminophen overdose. S-allylmercaptocysteine significantly suppressed hepatic cytochrome P450 2E1 (CYP2E1) activity and induction of inducible 70-kDa heat shock protein, a marker of acetaminophen arylation of protein. These results suggest that S-allylmercaptocysteine exerts its protective effect by inhibition of CYP2E1 activity, which leads to the suppression of acetaminophen arylation of hepatic protein.

Water-soluble organosulfur compounds of garlic inhibit fatty acid and triglyceride syntheses in cultured rat hepatocytes.

The putative hypolipidemic effect of garlic remains controversial. To gain further insight into the effect of garlic on lipid metabolism, the present study determined the inhibitory effects of water-soluble organosulfur compounds present in garlic on triglyceride (TG) and fatty acid synthesis in cultured rat hepatocytes. When incubated at 0.05 to 4.0 mmol/L with cultured hepatocytes, S-allyl cysteine (SAC) and S-propyl cysteine (SPC) decreased [2-14C]acetate incorporation into triglyceride in a concentration-dependent fashion achieving a maximal inhibition at 4.0 mmol/L of 43 and 51%, respectively. The rate of [2-14C]acetate incorporation into phosphlipids was depressed to a similar extent by SAC and SPC. SPC, SAC, S-ethyl cysteine (SEC), and gamma-glutamyl-S-methyl cysteine decreased [2-14C]acetate incorporation into fatty acid synthesis by 81, 59, 35, and 40%, respectively, at 2.0-4.0 mmol/L concentrations. Alliin, gamma-glutamyl-S-allyl cysteine, gamma-glutamyl-S-propyl cysteine S-allyl-N-acetyl cysteine, S-allylsulfonyl alanine, and S-methyl cysteine had no effect on fatty acid synthesis. The activities of lipogenic enzymes, fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PDH) were measured in cultured hepatocytes treated with the inhibitors. The activity of FAS in cells treated with 4.0 mmol/L SAC and SPC, respectively, was 32 and 27% lower than that of nontreated cells. Neither SAC nor SPC affected G6PDH activity. The results indicate that SAC, SEC, and SPC inhibit lipid biosynthesis in cultured rat hepatocytes, and further suggest that these S-alk(en)yl cysteines of garlic impair triglyceride synthesis in part due to decreased de novo fatty acid synthesis resulting from inhibition on FAS. Whether tissue concentrations of active garlic components can achieve levels required to inhibit TG synthesis in vivo warrants further investigation.

Suppression of Chemical Carcinogenesis by Water-Soluble Organosulfur Compounds

The chemopreventive effects of five water-soluble organosulfur compounds, S-methylcysteine (SMC) and four analogs, were examined on the promotion stage of diethylnitrosamine hepatocarcinogenesis in male F344 rats, using the medium-term bioassay (Ito test), which is based on the two-step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of a putative neoplastic lesion, glutathione S-transferase placental form (GST-P)--positive hepatocellular foci. SMC and cysteine significantly decreased the number and area of GST-P--positive foci when given in the promotion stage of the Ito test. When given during the initiation stage, these two organosulfur compounds also significantly inhibited focus formation. Liver ornithine decarboxylase activity after two thirds partial hepatectomy and the proportion of hepatocytes positive for proliferating cell nuclear antigen significantly decreased the number of aberrant crypt foci in the colon in a multiorgan carcinogenesis bioassay of rats. These results support SMC and cysteine as chemopreventive agents for hepatocarcinogenesis and colon carcinogenesis. Their intake may be of importance for cancer.

Antioxidant Health Effects of Aged Garlic Extract

Oxidative modification of DNA, proteins and lipids by reactive oxygen species (ROS) plays a role in aging and disease, including cardiovascular, neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic that are aged over a prolonged period to produce aged garlic extract (AGE) contain antioxidant phytochemicals that prevent oxidant damage. These include unique water-soluble organosulfur compounds, lipid-soluble organosulfur components and flavonoids, notably allixin and selenium. Long-term extraction of garlic (up to 20 mo) ages the extract, creating antioxidant properties by modifying unstable molecules with antioxidant activity, such as allicin, and increasing stable and highly bioavailable water-soluble organosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and increasing glutathione in the cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and inhibiting oxidative modification of LDL, thus protecting endothelial cells from the injury by the oxidized molecules, which contributes to atherosclerosis. AGE inhibits the activation of the oxidant-induced transcription factor, nuclear factor (NF)-kappa B, which has clinical significance in human immunodeficiency virus gene expression and atherogenesis. AGE protects DNA against free radical--mediated damage and mutations, inhibits multistep carcinogenesis and defends against ionizing radiation and UV-induced damage, including protection against some forms of UV-induced immunosuppression. AGE may have a role in protecting against loss of brain function in aging and possess other antiaging effects, as suggested by its ability to increase cognitive functions, memory and longevity in a senescence-accelerated mouse model. AGE has been shown to protect against the cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer therapy and against liver toxicity caused by carbon tetrachloride (an industrial chemical) and acetaminophen, an analgesic. Substantial experimental evidence shows the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease.

Mechanisms of Protection by S-Allylmercaptocysteine Against Acetaminophen-Induced Liver Injury in Mice

S-Allylmercaptocysteine (SAMC), one of the water-soluble organosulfur compounds in ethanol extracts of garlic (Allium sativum L.), has been shown to protect mice against acetaminophen (APAP)-induced liver injury. In this study, we examined the mechanisms underlying this hepatoprotection. SAMC (100 mg/kg, p.o.) given 2 and 24 hr before APAP administration (500 mg/kg, p.o.) suppressed the plasma alanine aminotransferase activity increases 3 to 12 hr after APAP administration significantly. The hepatic reduced glutathione levels of vehicle-pretreated mice decreased 1 to 6 hr after APAP administration, but SAMC pretreatment suppressed the reductions 1 to 6 hr after APAP administration significantly. These inhibitory effects of SAMC were dose-dependent (50–200 mg/kg) 6 hr after APAP administration. As SAMC pretreatment (50–200 mg/kg) suppressed hepatic cytochrome P450 2E1-dependent N-nitroso-dimethylamine demethylase activity significantly in a dose-dependent manner, we suggest that one of its protective mechanisms is inhibition of cytochrome P450 2E1 activity. SAMC pretreatment also suppressed the increase in hepatic lipid peroxidation and the decrease in hepatic reduced coenzyme Q9 (CoQ9H2) levels 6 hr after APAP administration. The hepatic CoQ9H2 content of the SAMC pretreatment group was maintained at the normal level. Therefore, we suggest that another hepatoprotective mechanism of SAMC may be attributable to its antioxidant activity.

Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase.

Sulfur-containing substances derived from garlic and onion have been shown to prevent experimental carcinogenesis. One of the hypotheses explaining the mechanisms of the chemopreventive activity of these substances is that they activate detoxification systems such as glutathione S-transferase (GST). In this study the effects of S-allylcysteine (SAC), a water-soluble organosulfur compound derived from garlic, on GST activities in the liver, small intestine and colon were investigated. Additionally, we examined SAC for chemopreventive effects on aberrant crypt foci, which are the most likely precursors of colon cancers. In the rat colonic aberrant crypt assay administration of SAC during the initiation period decreased the number of aberrant crypt foci by 33 and 54% in groups given 40 or 80% maximum tolerated dose (MTD) of SAC respectively. The number of aberrant crypt foci, however, was not changed when SAC was given during the promotion period. GST activity in the liver was increased significantly by 41% 12 h after a single oral administration of 3.5 mmol/kg SAC and this elevated GST level was maintained over a 72 h period. GST levels were increased significantly by the administration of SAC (1.8 mmol/kg/ day for 3 days) not only in the liver but also in the proximal and middle small bowel. Isozyme levels of GST after administration of SAC were also determined using Western blotting. Hepatic GST-alpha and GST-mu were significantly increased by 35 and 42% respectively after oral administration of SAC. GST-pi levels were lower than the detection limit (130 ng/mg/protein) in both the control and SAC-treated groups. These results strongly support the previous working hypothesis that SAC exhibits chemopreventive activity by exerting specific effects on carcinogen detoxification systems.