Thursday, 31 October 2013

Phytochemicals in Foods - 13 Health Benefits of Dithiolthiones (isothiocyanates)

Dithiolthiones are phytochemicals in the class of Organosulfides, found abundantly in cruciferous vegetables, garden sorrel, horseradish, etc.

Health Benefits
1. Anti acetaminophen hepatotoxicity
In the investigation of Anethol dithiolthione (ADT), usually prescribed as a choleretic drug, given orally 1 hour prior to acetaminophen (AAP) (450 mg/kg intraperitoneally) in Swiss female mice, found that ADT exhibited an hepatoprotective potency at doses as low as 10 mg/kg relative to serum aminotransferase activities and hepatic glutathione related enzyme system (glutathione reductase, peroxidase, transferase), according to "Protective effect of anethol dithiolthione against acetaminophen hepatotoxicity in mice" by Warnet JM, Christen MO, Thevenin M, Biard D, Jacqueson A, Claude JR.(1)

2. Chemopreventive efficacy
in the observation of two exposure regimens used to compare the efficacies of early (Regimen-A) versus late (Regimen-B) intervention in prevention of lung tumorigenesis in A/J mice, indicated that Evaluation of lung tumor multiplicity following exposure to oltipraz showed that oltipraz inhibited the tumor development in a dose-dependent manner (10-100 mg/m(3)) with inhibition ranging from 37 to 53% in Regimen A and 51% in Regimen B, when compared with the B[a]P group. Analysis of the tumor incidence showed that 81.5% of the animals had 10 or more tumors in the B[a]P group, whereas, in oltipraz exposure groups, there was a significant decrease in Regimen A (24-36%) and in Regimen B (42%), according to "The chemopreventive efficacy of inhaled oltipraz particulates in the B[a]P-induced A/J mouse lung adenoma model" by Sharma S, Gao P, Steele VE.(2)

3. Detoxication of xenobiotics
In the testing The dithiolthiones, oltipraz, ADT, 116L and 129L, in mice and in rats, oltipraz. Intragastric administration of dithiolthiones (oltipraz, ADT or 116L; two doses each of 1 g/kg body weight) found that Dithiolthiones present in cabbage may play a role in the protective actions of diets high in vegetables against the toxic actions of xenobiotics, according to "Biochemical effects of dithiolthiones' by Ansher SS, Dolan P, Bueding E.(3)

4. Antioxidants
In the examination of the role of glutathione (GSH) in the regulation of this adhesion phenomenon and in the increased tyrosine phosphorylation induced by ROS, found that ADT reduced both PMN adhesion to ROS-stimulated human umbilical vein endothelial cells (HUVEC) and tyrosine phosphorylation of p125FAK and paxillin. ADT increased redox status by increasing intracellular GSH content in oxidized cells. These results show that GSH can reverse the effect of oxidation on tyrosine kinase activation and phosphorylation, and thus plays an important role in cell signaling. They also confirm the antioxidant activity of ADT, according to "Anethole dithiolethione regulates oxidant-induced tyrosine kinase activation in endothelial cells" by Ben-Mahdi MH, Gozin A, Driss F, Andrieu V, Christen MO, Pasquier C.(4)

5. Aflatoxin B1 contamination
In the study of the influence of oltipraz and a second dithiolthione, (1,2) dithiolo (4,3-c)-1,2-dithiole-3,6 dithione (DDD) on bovine hepatic aflatoxin B1 biotransformation, found that Oltipraz inhibited aflatoxin B1 metabolism as no aflatoxin M1 and no aflatoxin B1-dihydrodiol, the second metabolite found in bovine hepatocytes, was formed. DDD did not significantly inhibit aflatoxin B1 metabolism. It could be demonstrated that the inhibition of aflatoxin B1 metabolism was due to the inhibition of several cytochrome P450 enzyme activities by oltipraz. In contrast, DDD inhibited only ethoxyresorufin O-deethylation activity, according to "Inhibition of aflatoxin M1 production by bovine hepatocytes after intervention with oltipraz" by Kuilman ME, Maas RF, Woutersen-van Nijnanten FM, Fink-Gremmels J.(5)

6. Cancer prevention
In the investigation of The critical role of the glutathione S-transferase (GST) and their importance in cancer prevention and susceptibility, clinical studies revealed that the GST activity of blood lymphocytes from individuals with either a personal or family history of colorectal cancer or a personal history of colon polyps was decreased significantly when compared to that of healthy controls. Phase 1 clinical evaluation of oltipraz has demonstrated its ability to induce GST activity as well as the level of transcripts encoding gamma-glutamylcysteine synthetase (gamma-GCS) and DT-diaphorase in the colon mucosa of individuals at increased risk for colorectal cancer. The observed correlation between the posttreatment response in blood lymphocytes and colon mucosa suggested that blood lymphocytes may be used in future trials as a surrogate biomarker of the responsiveness of colon tissue to chemopreventive regimens, according to "Glutathione S-transferases--biomarkers of cancer risk and chemopreventive response" by Clapper ML, Szarka CE.(6)

7. Anti nephrotoxicity
in the determination of s the effects of ADT on hexachloro-1,3-butadiene (HCBD)-induced nephrotoxicity in the rat and the mechanism of its action, found that ADT protects rats against HCBD-induced nephrotoxicity by a mechanism that does not involve the modulation of HCBD conjugation with liver GSH, nor the modulation of the kidney NPSH level and beta-lyase activity. The mechanism of protection conferred to rats by an ADT pretreatment against HCBD-induced nephrotoxicity appears to take place in the kidney at a step beyond the generation of ultimate toxic metabolites derived from PCBC, according to 'Assessment of the role of glutathione conjugation in the protection afforded by anethol dithiolthione against hexachloro-1,3-butadiene-induced nephrotoxicity" by Bouthillier L, Charbonneau M, Brodeur J.(7)

8. Inhibition of platelet aggregation
in the investigation of Anethole dithiolthione (ADT) (10 mumol/l) inhibition of platelet aggregation and the formation of thromboxane (Tx)B2 in plasma in response to adenosine diphosphate (ADP), epinephrine and arachidonic acid (AA), indicated that ADT had no additive effect on the inhibition of thrombin-induced platelet aggregation by acetylsalicylic acid. ADT was a more effective inhibitor of AA-induced platelet aggregation than butylated hydroxytoluene. ADT inhibited the release of 3H-AA from platelet phospholipids in response to ADP and collagen. It is suggested that ADT inhibits platelet aggregation by inhibiting thromboxane synthesis and preventing AA release, according to "Effect of anethole dithiolthione on human platelet aggregation" by Selley ML, McGuiness JA, Bartlett MR, Ardlie NG.(8)

9. Early colon carcinogenesis
in the study of the effect of dietary oltipraz on liver and colonic mucosal enzymes and DNA adducts in evaluating the modulating role of this agent during the early period of azoxymethane (AOM)-induced carcinogenesis, showed that dietary oltipraz enhances the colonic and liver glutathione S-transferase activity and reduced the formation of DNA adducts. In addition, dietary oltipraz modulates liver and colonic ODC and TPK activities that have been shown to play a role in tumor promotion, according to "Effect of oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] on azoxymethane-induced biochemical changes related to early colon carcinogenesis in male F344 rats" by Rao CV, Nayini J, Reddy BS.(9)

10. Lipid peroxidation
in the observation of the drug anisyldithiolthione (ADT) acted as a good inhibitor of lipid peroxidation induced in rat liver microsomes either chemically by FeSO4 and reducing agents (cysteine or ascorbate) or enzymatically by NADPH and CC14, showed that at doses as low as 5 mg per kg it completely suppressed ethane exhalation by acetaminophen-intoxicated mice and also protected them very efficiently against mortality caused by acetaminophen overdose. The inhibitory effect of ADT toward lipid peroxidation seems to be linked to the presence of its dithiolthione function, according to "A new potent inhibitor of lipid peroxidation in vitro and in vivo, the hepatoprotective drug anisyldithiolthione" by Mansuy D, Sassi A, Dansette PM, Plat M.(10)

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