The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride.

Allyl sulfides, e.g., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), are principal constituents of garlic oil. In the present study, we investigated the in vivo effect of these sulfides on the phase I and phase II drug-metabolizing enzymes, and elucidated their structure-function relationship. A highly purified form of each sulfide (more than 99% purity) was administered i.p. as a bolus to rats at a concentration of 10 or 100 micromol/kg body weight for 14 consecutive days. As to the phase I enzymes, DAS (100 micromol/kg) slightly but significantly increased cytochrome P-450 (CYP) 2E1 activity (1.6-fold vs. control), whereas DADS and DATS did not affect it or the hepatic total CYP level or CYP1A1/2 activity. With respect to the phase II enzymes, DATS (10 micromol/kg) and DADS at a 10-fold higher dose (100 micromol/kg) significantly increased the activities of glutathione S-transferase, quinone reductase, and antioxidative enzyme glutathione peroxidase; whereas DAS did not. In the carbon tetrachloride (CCl4)-induced acute liver injury model of rats, either DATS (10 micromol/kg) or DADS (100 micromol/kg) significantly reduced the injury caused by the induction of phase II enzymes with CCl4. In conclusion, the sulfides affected both phase I and phase II enzymes, the former being stimulated by the monosulfide only and the latter, strongly by the trisulfide and weakly by the disulfide. Therefore, the polysulfide DATS may be one of the important factors in garlic oil that protects our body against the injury caused by radical molecules encountered in daily life.     

Effect of garlic sulfur compounds on neutrophil infiltration and damage to the intestinal mucosa by endotoxin in rats

We investigated the protective effects of garlic sulfur compounds (GSCs), specifically, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), on endotoxin-induced intestinal damage. Wistar rats received by gavage 0.125 or 0.025 mmol/kg body wt of each GSC or the vehicle (corn oil; 2 mL/kg body wt) every other day for 2 weeks before being injected with endotoxin (ip, 5 mg/kg body wt). Control rats were administered corn oil and were injected with sterile saline. Rats were killed at 18 h after injection. Both doses of DAS suppressed endotoxin-induced neutrophilia, serum levels of sICAM-1 and CINC-1, cellular CD11b on neutrophils, and intestinal contents of ICAM-1, CINC-1, TNF-alpha, and IL-1beta (p<0.05). DADS suppressed endotoxin-induced intestinal contents of ICAM-1, TNF-alpha, and IL-1beta at both doses, but only suppressed the serum sICAM-1 level and cellular CD11b on neutrophils at the low dose (p<0.05). DATS did not ameliorate the endotoxin-induced serum level of sICAM-1 or CINC-1 but suppressed intestinal IL-1beta at both doses. The low but not the high dose of DATS also ameliorated the intestinal contents of ICAM-1 and TNF-alpha (p<0.05). All GSCs reversed endotoxin-induced neutrophil infiltration and damage in the intestine, and the order of the effects of these GSCs to normalize intestinal morphology was DAS>DADS>DATS.     

Diallyl sulfide,diallyl disulfide,and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase‐2, ‐7, and ‐9 expressions

Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) are major organosulfur compounds exiting in garlic (Allium sativum). These compounds are reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation, and they also induce cytotoxicity and induction of apoptosis in human cancer cells. Although these compounds show wide spectrum of biological activities, there are no reports to show that DAS, DADS, and DATS affected migration and invasion of human colon cancer cells, and their exact molecular mechanisms are not well investigated. Therefore, the purpose of this study was to determine whether DAS, DADS, and DATS affected the invasion and migration abilities of colo 205 human colon cancer cells. The results indicate that DAS, DADS, and DATS at 10 and 25 μM inhibited the migration and invasion of colo 205 cells in the order of DATS < DADS < DAS. DATS is the highest for inhibition of migration and invasion of colo 205 cells. DAS, DADS, and DATS induce downregulation expression of PI3K, Ras, MEKK3, MKK7, ERK1/2, JNK1/2, and p38 and then lead to the inhibition of MMP‐2, ‐7, and ‐9. DAS, DADS, and DATS inhibited NF‐κB and COX‐2 for leading to the inhibition of cell proliferation. Taken together, these results demonstrated that application of DAS, DADS, and DATS might serve as potential antimetastatic drugs. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 479–488, 2013.     

Antidiabetic effect of garlic oil but not diallyl disulfide in rats with streptozotocin-induced diabetes.

We investigated the effects of garlic oil and diallyl disulfide (DADS) on glycemic control and renal function in rats with streptozotocin-induced diabetes. Rats received by gavage garlic oil (100 mg/kg body wt) or DADS (40 or 80 mg/kg body wt) every other day until 16 weeks after the induction of diabetes. The control rats were treated with corn oil only. Neither garlic oil nor DADS significantly affected fasting blood glucose concentrations throughout the investigation period. Garlic oil did not affect oral glucose tolerance in diabetes acutely but significantly improved oral glucose tolerance at 4, 8, 12, and 16 weeks and significantly ameliorated proteinuria at the end of 16 weeks. DADS did not significantly affect oral glucose tolerance or renal function. Diabetic rats fed 80 mg DADS/kg body wt had a significantly lower rate of body weight gain and a significantly lower ratio of muscle weight to body weight than did vehicle-treated diabetic rats. In conclusion, long-term treatment of diabetes with garlic oil can improve oral glucose tolerance and renal function in diabetes but not through the action of DADS. High doses of DADS may further complicate the metabolic disturbances in diabetes.     

Differential effects of allyl sulfides from garlic essential oil on cell cycle regulation in human liver tumor cells

In this study, diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS), which are major organosulfur compounds (OSCs) of garlic, were used as experimental materials to investigate their modulation effects on cell viability and cell cycle in human liver tumor cells (J5). According to the results of cell viability assay, 50 or 100 μM DATS significantly decreased the cell viability as compared with the control (P < 0.05) in dose and time dependent relations. Phenomena of cell number loss, shape deformation and lysis were observed after treatment with 100 μM DATS for 24 h. Cell cycle studies showed that J5 cells were significantly arrested in G2/M phase as the cells were treated with 100 μM DADS, 10, 50 or 100 μM DATS for 24 h (P < 0.05). DATS was more effective in arresting cells in G2/M phase than DADS, and the phenomena of arresting J5 cells in G2/M phase increased obviously in dose and time dependent relations. According to the Western blot analysis, DATS decreased cyclin-dependent kinase (Cdks)-Cdk7 (i.e. Cdc2 activate kinase) protein levels in J5 cells but increased cyclin B1 protein level. The modulation potency to cyclin B1 and Cdk7 expressions was in the order of DATS > DADS > DAS. The modulation potency to cyclin B1 and Cdk7 protein levels increased with increasing in DATS concentration and culture time. In conclusion, DATS might affect cell viability and cell morphological changes in J5 cells and lead cells to be arrested in G2/M phase via controlling the expression of cyclin B1 and Cdk7 in J5 cells, and the controlling action might relate to the sulfuric atom numbers in the structures of all these allyl sulfides.     

Potential beneficial effects of garlic in oncohematology

The use of non-conventional medicines, especially herbal medicine, is common in patients with cancers including haematologic malignancies. Diet components may also modify the risk of cancer through the influence on multiple processes, including DNA repair, cell proliferation and apoptosis. Garlic (Allium sativum), considered either food or herbal medicine, possesses antimutagenic and antiproliferative properties that can be used in anticancer interventions. We analyzed literature data on effects of garlic and garlic compounds which can serve as basic information to design clinical approach in oncohematology. Garlic contains water soluble and oil-soluble sulfur compounds. The latter are responsible for anticancer effects exerted through multiple mechanisms such as: inhibition of metabolic carcinogenic activation, arrest of cell cycle, antioxidant and pro-apoptotic action. Evidence about the effects of main sulfur compounds diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), ajoene and S-allylmercaptocysteine (SAMC) in oncohematology was described. Our research highlights that data on garlic in oncohematology are essentially represented by pre-clinical studies. Although these studies must be considered as preliminary, they provided insight into biological activities of garlic compounds and support a rationale for the use of substances such as DAS, DADS, DATS and ajoene as promising anticancer agents in oncohematology.     

Molecular mechanisms for the anti-cancer effects of diallyl disulfide

Considerable evidence in recent years suggests that garlic has anti-proliferative effects against various types of cancer. Garlic contains water-soluble and oil-soluble sulfur compounds. Oil-soluble compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and ajoene are more effective than water-soluble compounds in protection against cancer. DADS, a major organosulfur compound derived from garlic, can decrease carcinogen-induced cancers in experimental animals and inhibit the proliferation of various types of cancer cells. Its mechanisms of action include: the activation of metabolizing enzymes that detoxify carcinogens; suppression of the formation of DNA adducts; antioxidant effects; regulation of cell-cycle arrest; induction of apoptosis and differentiation; histone modification; and inhibition of angiogenesis and invasion. These topics are discussed in depth in this review.     

Simultaneous determination of diallyl trisulfide and diallyl disulfide in rat blood by gas chromatography with electron-capture detection

A simple, rapid and sensitive method has been developed and validated for the simultaneous quantification of diallyl trisulfide (DATS) and diallyl disulfide (DADS) in rat blood by gas chromatography with electron-capture detection. The analytes were prevented from degradation by addition of acetonitrile and extraction with hexane before gas chromatographic separation. Two calibration curves for DATS were linear over the range of 10-500 ng/mL and 0.2-20 microg/mL, with typical r values of 0.9989 and 0.9993, respectively. Similarly, two calibration curves for DADS were linear in the concentration range of 50-5000 ng/mL and 1-30 microg/mL, with typical r values of 0.9989 and 0.9983, respectively. The limit of detection was less than 10 ng/mL for DATS and 50 ng/mL for DADS, and the assay was highly reproducible, considering the intra-, inter-day relative standard deviations (R.S.D.) below 12%. The developed procedure was successfully applied for the evaluation of the pharmacokinetics of garlic oil following iv administration at a single dose (10 mg) of garlic oil in rats. The results show that the developed method is suitable for pharmacokinetic and therapeutic purposes of DATS and DADS.     

Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin

Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg body weight diallyl disulfide or diallyl trisulfide, or the vehicle (corn oil; 2 ml/kg body weight) every other day for 2 weeks before being injected with endotoxin (i.p., 5 mg/kg body weight). Control rats were administered with corn oil and were injected with sterile saline. Samples for the measurement of proinflammatory cytokines were collected 3 h after injection, and all other samples were collected 18 h after injection. The low dose of GO suppressed endotoxin-induced inducible nitric oxide synthase (iNOS) activity, ulceration, and apoptosis in the intestinal mucosa (P < 0.05). The high dose of GO significantly lowered the peripheral level of nitrate/nitrite and endotoxin-induced iNOS activity in the intestinal mucosa (P < 0.05) but worsened intestinal mucosal damage accompanied by elevated peripheral proinflammatory cytokines. Diallyl trisulfide but not diallyl disulfide showed similar toxic effect as that of high-dose GO. These results suggest the preventive effect and possible toxicity of garlic oil and its organosulfur compounds in endotoxin-induced systemic inflammation and intestinal damage.     

Effect of diallyl sulfide and diallyl disulfide, the active principles of garlic, on the aflatoxin B(1)-induced DNA damage in primary rat hepatocytes

The objective of this study was to investigate the effect of the active principles in garlic-- diallyl sulfide (DAS) and diallyl disulfide (DADS)--on aflatoxin B(1) (AFB(1))-induced DNA damage in primary rat hepatocytes. Primary rat hepatocytes, induced with DNA damage using 10 microM AFB(1) were used as an experimental model. According to the results of LDH leakage, 0.5 and 2 mM of DAS or 0.5 and 1 mM of DADS significantly increased the viability of hepatocytes compared with the AFB(1) controls after 4, 8 and 24 h treatment (P<0.05). According to the results of unscheduled DNA synthesis (UDS) test, 0.5 and 2 mM of DAS or 0.5 and 1 mM of DADS could significantly decrease the DNA damage induced by AFB(1) (P<0.05). Furthermore, 0.5 and 2 mM DAS or 0.5 and 1 mM DADS could increase the glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities as compared with the AFB(1) controls after 24 h treatment (P<0.05). Results of immunoblot analysis of cytosolic GST isoenzyme indicate that the levels of GST isoform Ya, Yb2 and Yc were markedly increased after treatment with 0.5 and 2 mM DAS or 0.5 and 1 mM DADS compared with the AFB(1) control. These results indicate that 0.5 and 2 mM DAS or 0.5 and 1 mM DADS might protect hepatocytes from AFB(1)-induced DNA damage via increasing the activities of GST and GPx.     

Modulation of cytochrome P450 enzymes by organosulfur compounds from garlic

Organosulfur compounds (OSCs) derived from garlic have been studied for the ability to inhibit experimental cancer in various animal models, primarily through modification of carcinogen detoxification enzymes, such as cytochrome P450 (CYP) enzymes. OSCs vary in structural and physical properties, and a detailed analysis of these properties has not been performed with respect to their ability of inhibit chemically-induced colon cancer development. Gastric intubation of rats with a single dose of 200 mg/kg diallyl sulfide (DAS), diallyl disulfide (DADS), and allyl methyl sulfide (AMS) decreased hepatic CYP2E1 protein by 45%, 25% and 47%, respectively, and this inhibition was sustained after 1, 4 and 8 weeks of treatment by these compounds. Dipropyl sulfide (DPS), dipropyl disulfide (DPDS), propyl methyl sulfide (PMS) and S-allylcysteine (SAC) did not inhibit hepatic CYP2E1 protein expression, nor did any of the OSCs affect CYP2E1 mRNA levels. A single dose of 200 mg/kg DAS and AMS increased hepatic CYP1A2 protein (but not mRNA) by 282% and 70%, and DAS increased CYP1A1 protein levels by 684%. Daily treatment for 1, 4 and 8 weeks with 200 mg/kg DAS and AMS resulted in time-dependent increases in hepatic CYP1A1 and CYP1A2 protein levels to a maximum of 600% and 50% for DAS, and 1600% and 240% for AMS after 8 weeks. Dosing with 200 mg/kg of each of the OSCs used in this study increased hepatic CYP3A2 protein levels at all time points. Dosing for 8 weeks with 200 mg/kg DAS, but not AMS or lower doses of DAS, induced bile duct obstruction and focal areas of necrosis. These results indicate that OSCs present in garlic, including DAS and AMS, may be beneficial in inhibiting chemically-induced colon cancer, but that longer dosing with higher concentrations of DAS may elicit minor hepatic toxicity.     

Effect of diallyl sulfide, a naturally occurring anti-carcinogen, on glutathione-dependent detoxification enzymes of female CD-1 mouse tissues

The present studies were undertaken to elucidate the mechanism(s) of the anti-neoplastic effect of diallyl sulfide (allyl sulfide, DAS), a naturally occurring organosulfide abundant in vegetables of the Allium genus, against benzo[a]pyrene (B[a]P)-induced carcinogenesis in the mouse. DAS treatment caused a significant increase in glutathione S-transferase (GST) activity, an enzyme system responsible for detoxification of a variety of electrophilic xenobiotics including several harmful B[a]P metabolites, of mouse stomach in a dose-dependent manner. This activity in the stomach of mice treated with 25, 50 and 75 mumol DAS was higher by 1.13-, 1.20- and 1.58-fold, respectively, when compared to the control. Purification and quantitation of GST from equal amounts (1.2 g) of control and 50 mumol DAS-treated mice stomach tissues demonstrated that elevation in activity occurred as a result of increased de novo synthesis of the enzyme protein. DAS treatment also resulted in increased pulmonary GST activity, but not in a dose-dependent fashion. On the other hand, treatment of mice with DAS did not alter hepatic GST activity. Interestingly, a small but statistically significant (P less than or equal to 0.05) reduction in kidney GST activity was observed in mice treated with 50 or 75 mumol DAS, as compared to the control. The effect of DAS treatment was also assessed on glutathione (GSH) peroxidase activity, another GSH-dependent detoxification enzyme, in mouse tissues. Treatment of animals with 25, 50 and 75 mumol DAS increased stomach GSH peroxidase activity by 1.64-, 1.93- and 2.52-fold, respectively, over the control. This enzyme activity in the lungs of mice treated with 25, 50 and 75 mumol DAS was higher by 1.44-, 1.54- and 1.21-fold, respectively, when compared to the control. On the other hand, GSH peroxidase activity in liver and kidney was unchanged by DAS treatment. These results suggest that DAS and perhaps other naturally occurring organosulfur compounds may exert an anti-neoplastic effect by modulating GSH-dependent detoxification enzymes.     

Effect of the active principle of garlic—Diallyl sulfide—On cell viability,detoxification capability and the antioxidation system of primary rat hepatocytes

The objectives of this study were to investigate the effects of various concentrations and incubation time intervals of diallyl sulfide (DAS), an active principle of garlic, on cell viability, and glutathione (GSH) concentration and its related enzymes activities in rat hepatocytes. According to the results of lactate dehydrogenase (LDH) leakage and microscopic examination, 0.5 or 1 mM DAS treatment did not have any adverse effects on the viability of hepatocytes. Intracellular GSH contents of cells treated with 0.5 and 1 mM DAS (58.6 and 66.4 nmol GSH/mg protein, respectively) were higher than in the controls (54.2 nmol GSH/mg protein), around 8–23%, at 24 hr of incubation; a significant difference (P < 0.05) was observed for 1 mM DAS treatment at 48 hr. This phenomenon is beneficial to the detoxification and antioxidation capabilities of hepatocytes. Further, when the hepatocytes were treated with 0.5 or 1 mM DAS, the activities of glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GRd) were almost the same as those of the controls. On the other hand, treatment with 5 mM DAS was associated with a significant decrease (P < 0.05) in cell viability, namely in increased LDH leakage (50% at 24-hr treatment), significant changes in the morphology of the hepatocytes, low intracellular GSH level (45% lower than in the controls at 24-hr treatment), and low activities of GST, GPx and Grd.     

Effects of diallyl tetrasulfide on cadmium-induced oxidative damage in the liver of rats

The protective efficacy of diallyl tetrasulfide (DTS) from garlic on liver injury induced by cadmium (Cd) was investigated. In this study, Cd (3 mg/kg body weight) was administered subcutaneously for 3 weeks to induce toxicity. DTS was administered orally (10, 20 and 40 mg/kg body weight) for 3 weeks with subcutaneous (sc) injection of Cd. Cd-induced liver damage was evidenced from increased activities of serum hepatic enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase, with significant elevation of lipid peroxidation indices (thiobarbituric acid reactive substances and hydroperoxides) and protein carbonyl groups in the liver. Rats subjected to Cd toxicity also showed a decline in the levels of total thiols, reduced glutathione (GSH), vitamin C and vitamin E, accompanied by an increased accumulation of Cd, and significantly decreased activities of superoxide dismutase, catalase (CAT), glutathione peroxidase, glutathione-S-transferase (GST), glutathione reductase, and glucose-6-phosphate dehydrogenase in the liver. Administration of DTS at 40 mg/kg body weight significantly normalised the activities of hepatic marker enzymes, compared to other doses of DTS (10 and 20 mg/kg body weight). In addition, DTS (40 mg/kg body weight) significantly reduced the accumulation of Cd and the level of lipid peroxidation, and restored the level of antioxidant defense in the liver. Histological studies also showed that administration of DTS to Cd-treated rats resulted in a marked improvement of hepatocytes morphology with mild portal inflammation. Our results suggest that DTS might play a vital role in protecting Cd-induced oxidative damage in the liver.     

Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants

Glutathione S-transferases and glutathione play an important role in the detoxification of most toxic agents. In the present study, the protective effects of some antioxidants (L-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon tetrachloride-induced changes in the activity of alanine amino transferase (ALT), aspartate amino transferase (AST), glutathione S-transferase (GST), and the level of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were studied. The activities of ALT, and AST were assayed in plasma, whereas the activity of GST and the levels of GSH and TBARS were determined in the livers of rats. The current study included two experiments. In the first experiment, animals received single oral dose of CCl4 (400 mg/kg body weight) after administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg b.w.) as single oral doses. In the second experiment, rats received repeated oral doses of antioxidants for 12 consecutive days followed by a single oral dose of CCl4 on the 13th day and killed after that by 24 h. Treatment of male rats with CCl4 significantly increased the activity of ALT and AST in plasma, and the levels of both GSH and TBARS in the liver. On the other hand, CCl4 inhibited the activity of GST after single dose treatment. Single-dose treatments of rats with AA, VE or garlic prior to the administration of CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to the normal control level. However, repeated dose treatments with these agents restored such alterations to the normal level. We observed that VE is more effective than AA and garlic in restoring the inhibition of GST activity caused by CCl4 to the normal level after single dose treatments. On the other hand, AA and VE are more effective than garlic in restoring the induced TBARS level caused by CCl4 to the normal control level after repeated dose treatments. It has been observed that the tested antioxidants were able to antagonize the toxic effects of CCl4, and such counteracting effects were more pronounced when they were administered as repeated doses prior to administration of CCl4.     

Effects of the garlic compounds diallyl sulphide and diallyl disulphide on arylamine N-acetyltransferase activity in Klebsiella pneumoniae

Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene (2-AF) were determined in the bacterium Klebsiella pneumoniae. Cytosols or suspensions of K. pneumoniae with or without specific concentrations of diallyl sulphide (DAS) or diallyl disulphide (DADS) as co-treatment showed different percentages of 2-AF acetylation. The data indicated that there was decreased NAT activity associated with increased levels of DAS or DADS in K. pneumoniae. In growth studies on K. pneumoniae it was demonstrated that DAS or DADS elicited a dose-dependent bacteriocide effect on K. pneumoniae. For the cytosol examinations, the apparent values of Km and Vmax were 0.96+/-0.09 mM and 7.87+/-0.79 nmol min(-1) mg(-1) protein, respectively, for 2-AF. However, when DAS or DADS was added to the reaction mixtures, the apparent values of Km and Vmax were 0.16+/-0.04 mM and 0.99+/-0.16 nmol min(-1) mg(-1) protein with DAS, respectively, and 0.14+/-0.18 mM and 0.85+/-0.10 nmol min(-1) mg(-1) protein with DADS, respectively, for 2-AF. For the intact bacteria examination, the apparent values of Km and Vmax were 0.57+/-0.06 mM and 2.00+/-0.14 nmol min(-1) per 10x10(10) CFU, respectively, for 2-AF. However, when DAS or DADS was added to the reaction mixtures, the apparent of values of Km and Vmax were 0.41+/-0.04 mM and 1.30+/-0.10 nmol min(-1) per 10x10(10) CFU with DAS, respectively, and 0.34+/-0.04 mM and 1.08+/-0.08 nmol min(-1) per 10x10(10) CFU with DADS, respectively, for 2-AF. This report is the first demonstration to show that the garlic components DAS and DADS would affect K. pneumoniae growth and NAT activity.     

Post-initiation modulating effects of allyl sulfides in rat hepatocarcinogenesis.

Effects of administration of diallyl sulfide (DAS) and diallyl disulfide (DADS) on the promotion stage of hepatocarcinogenesis were investigated in rats using the Ito model. They were compared with those of phenobarbital (PB), a well-known liver promoter in rats. Initiation was induced by a single dose of N-nitrosodiethylamine (NDEA) and 3 weeks later, a partial hepatectomy was conducted. Two weeks after the NDEA injection, rats received either 0.05% allyl sulfides, PB or both in their diet for 8 weeks. Feeding with DAS increased the number of liver preneoplastic foci by 63% with respect to the untreated group. However, rats fed DAS showed a lower foci development than rats fed PB. The DADS group did not differ from control group for any of the measured morphometric parameters. Simultaneous administration of DADS with PB partially reduced the promotional activity of PB whereas DAS co-treatment did not modify PB properties. These findings confirm that DAS can act as a promoter in rat liver but exerts no co-promoting effect. Conversely, DADS was found to have promotion-inhibiting ability, suggesting that DADS has greater value than DAS as a chemopreventive agent.     

Effects of garlic components diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity in human bladder tumor cells

Diallyl sulfide (DAS) and diallyl disulfide (DADS) were used to determine viability and inhibition of arylamine N-acetyltransferase (NAT) activity in human bladder tumor cells. The NAT activity was measured by high performance liquid chromatography assaying for the amounts of N-acetyl-2-aminofluorene (2-AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and remaining 2-aminofluorene (2-AF) and p-aminobenzoic acid (PABA). The viability, NAT activity and 2-AAF-DNA adduct formation in human bladder tumor cells was inhibited by DAS and DADS in a dose-dependent manner, i.e. the higher the concentration of DAS and DADS, the higher the inhibition of NAT activity and cell death. The data also indicated that DAS and DADS decrease the apparent values of Km and Vmax from human bladder tumor cells in both systems examined. This report is the first demonstration to show garlic components did affect human bladder tumor cell NAT activity.     

Effects Of Garlic Components Diallyl Sulfide And Diallyl Disulfide On Arylamine N-Acetyltransferase Activity In Human Bladder Tumor Cells

ABSTRACT

Diallyl sulfide (DAS) and diallyl disulfide (DADS) were used to determine viability and inhibition of arylamine N-acetyltransferase (NAT) activity in human bladder tumor cells. The NAT activity was measured by high performance liquid chromatography assaying for the amounts of N-acetyl-2-aminofluorene (2-AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and remaining 2-aminofluorene (2-AF) and p-aminobenzoic acid (PABA). The viability, NAT activity and 2-AAF-DNA adduct formation in human bladder tumor cells was inhibited by DAS and DADS in a dose-dependent manner, i.e. the higher the concentration of DAS and DADS, the higher the inhibition of NAT activity and cell death. The data also indicated that DAS and DADS decrease the apparent values of Km and Vmaxfrom human bladder tumor cells in both systems examined. This report is the first demonstration to show garlic components did affect human bladder tumor cell NAT activity.