Abstract
In mice, diethyldithiocarbamate (dithiocarb, 100 mg/kg i.p.) completely prevented the increments of serum enzyme activities (GOT, GPT, SDH) induced by oral administration of carbon tetrachloride (0.1 ml/kg), allyl alcohol (0.05 ml/kg), bromobenzene (0.25 ml/kg), and thioacetamide (50 mg/kg). In this respect, cysteine (200 mg/kg i.p.) was active against CCl4 and bromobenzene, cysteamine (100 mg/kg i.p.) against CCl4 and allyl alcohol, penicillamine (100 mg/kg i.p.) against allyl alcohol, thiazolidine carbonic acid (100 mg/kg i.p.) against bromobenzene, and thioctic acid (100 mg/kg i.p.) against allyl alcohol and thioacetamide. Dimercaprol (100 mg/kg i.p.) had a weak antidotal effect only against allyl alcohol poisoning. None of the tested antidotes inhibited serum enzyme elevations evoked by dimethyl nitrosamine (100 mg/kg p.o.). These findings prove the antihepatotoxic activity of diethyldithiocarbamate to be superior to that of all other thio compounds under observation.
The lowest dose of dithiocarb active against carbon tetrachloride was 25 mg/kg i.p. The dose-response curves for serum-enzyme elevations induced by carbon tetrachloride (0.1–4 ml/kg p.o.) were shifted to the right under the influence of dithiocarb indicating a competitive antagonism. Dithiocarb (100 mg/kg i.p.) depressed the p-hydroxylation of aniline in the 9000 x g liver homogenate supernatant of mice by about 55%. Thus, the antihepatotoxic activity of dithiocarb seems to be the consequence of a decreased oxidase activity.
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References
Ammon, R., Berninger, H., Haas, H. J., Landsberg, I.: Thioacetamid-Sulfoxid, ein Stoffwechselprodukt des Thioacetamids. Arzneimittel-Forsch. 17, 521–523 (1967)
Bini, A., Vecchi, G., Vivoli, G., Vannini, V., Cessi, C.:Detection of early metabolites in rat liver after administration of CCl4 and CBrCl3. Pharmacol. Res. Commun. 7, 143–149 (1975)
Eger, W.: Über Cystein, Homocystein, Cystathionin und Cysteamin als nekrotrope Leberschutzstoffe in Verbindung mit Traubenzucker und Fruchtzucker. Medizinische 17, 618–623 (1957)
Fowler, J. S. L.: Carbon tetrachloride metabolism in the rabbit. Brit. J. Pharmacol. 37, 733–737 (1969)
Frimmer, M., Waldvogel, A., Weil, G.: Schutzwirkung von Thioctsäure gegen die Kalium-freisetzende Wirkung des Phalloidins an der isoliert perfundierten Rattenleber. Klin. Wschr. 46, 1281–1289 (1968)
Frimmer, M., Petzinger, E., Homann, J.: Phalloidinantagonisten. 4. Mitteilung: Thioctsäure, SH-Verbindungen, Rifampicin, Choleretika, Dexamethason, Östradiol, unspezifische Hemmstoffe und unwirksame Verbindungen. Arzneimittel-Forsch. 25, 1881–1884 (1975)
Gutbrod, H., Kornberger, E. J., Stille, G., Wolf, V.: Eigenschaften einer neuen antinekrotischen Kombination für die Behandlung akuter Leberschäden. Acta hepat. (Hamburg) 5, 1–12 (1957)
Homburg, Chemiewerk; Thioctacid (Thioctsäure Homburg). Frankfurt 1975
Hunter, A. L., Neal, R. A.: Inhibition of hepatic mixed-function oxidase activity in vitro and in vivo by various thionosulfur-containing compounds. Biochem. Pharmacol. 24, 2199–2205 (1975)
Janovics, T., Tako, J.: Die Anwendung von 2,3-Dimercaptopropanol (BAL) bei diffusen Leberparenchymschädigungen. Schweiz. med. Wschr. 80, 933–936 (1950)
Jollow, D. J., Mitchell, J. R., Zampaglione, N., Gillette, J. R.: Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenze oxide as the hepatotoxic metabolite. Pharmacology (Basel) 11, 151–169 (1974)
Kirnberger, E. J., Braun, W., Stille, G., Wolf, V.: Beziehungen zwischen Leberschutz und Zuckerstoffwechsel. Arzneimittel-Forsch. 8, 72–76 (1958)
Lange, P., Jung, F.: Die Verringerung der Lebertoxizität von Tetrachlorkohlenstoff durch Diäthyldithiocarbamat und 3-(o-Tolyl)-4-(nitro)-sydnon. Acta biol. med. germ. 27, 425–434 (1971)
Lange, J., Schumacher, K., Witscher, H. P.: Die Behandlung der chronisch-aggressiven Hepatitis mit d-Penicillamin. Dtsch. med. Wschr. 96, 139–145 (1971)
Legros, J.: Paracetamol and the liver. Animal studies — a theoretical basis for treatment. J. int. Med. Res. 4, (Suppl. 4), 46–54 (1976)
Lieber, C. S., Rubin, E., De Carli, L. M.: Hepatic microsomal ethanol oxidizing system (MEOS): differentiation from alcohol dehydrogenase and NADPH oxidase. Biochem. biophys. Res. Commun. 40, 858–865 (1970)
Lutz, L. M., Glende, E. A., Recknagel, R. O.: Protection by diethyldithiocarbamate against carbon tetrachloride lethality in rats and against carbon tetrachloride-induced lipid peroxidation in vitro. Biochem. Pharmacol. 22, 1729–1734 (1973)
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Davis, D. C., Gillette, J. R., Brodie, B. B.: Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J. Pharmacol. exp. Ther. 187, 185–194 (1973)
Rees, K. R., Tarlow, M. J.: The hepatotoxic action of allyl formate. Biochem. J. 104, 757–761 (1967)
Reid, W. D., Christie, B., Eichelbaum, M., Krishna, G.: 3-methyl-cholanthrene blocks hepatic necrosis induced by administration of bromobenzene or carbon tetrachloride. Exp. molec. Path. 15, 363–372 (1971)
Reynolds, E. S., Moslen, M. T.: Chemical modulation of early carbon tetrachloride liver injury. Toxicol. appl. Pharmacol. 29, 377–388 (1974)
Sakaguchi, T., Nishimura, H., Masuda, K., Tsuge, I., Onishi, K., Tatsumi, H.: The relationship between chemical structure and protective effect of dithiocarbamate derivates against experimental hepatic injury induced by carbon tetrachloride administration in rats. Biochem. Pharmacol. 15, 756–758 (1966)
Schlicht, I.: Autoradiographische und radiochromatographische Untersuchungen der Verteilung und des Stoffwechsels von Thioacetamid. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 268, 310–322 (1971)
Strömme, J. H.: Metabolism of disulfiram and diethyldithiocarbamate in rats with demonstration of an in vivo ethanol-induced inhibition of the glucuronic acid conjugation of the thiol. Biochem. Pharmacol. 14, 393–410 (1965)
Strubelt, O., Siegers, C.-P., Schütt, Atsuko: The curative effects of cysteamine, cysteine and dithiocarb in experimental paracetamol poisoning. Arch. Toxicol. 33, 55–64 (1974)
Sunderman, F. W.: Diethyldithiocarbamate therapy of thallotoxicosis. Amer. J. med. Sci. 253, 107–118 (1967)
Sunderman, F. W., Sunderman, F. W., Jr.: Nickel poisoning. VIII. Dithiocarb: a new therapeutic agent for persons exposed to nickel carbonyl. Amer. J. med. Sci. 236, 26–31 (1958)
Tonkelaar, E. M., van Loogten, M. J.: Protective action of dithiocarbamates on experimental liver damage produced by carbon tetrachloride. Toxicol. appl. Pharmacol. 30, 96–106 (1974)
Varga, F., Mekes, J., Molnar, Z.: Die Leberschutzwirkung von Cystein, Homocysteinthiolacton und-N-Acetylhomocysteinthiolacton bei experimenteller Leberschädigung. Arzneimittel-Forsch. 13, 867–871 (1963)
Wilson, J. T., Frohman, L. A.: Concomitant association between high plasma levels of growth hormone and low hepatic mixed-function oxidase activity in the young rat. J. Pharmacol. exp. Ther. 189, 255–270 (1974)
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Siegers, C.P., Strubelt, O. & Völpel, M. The antihepatotoxic activity of dithiocarb as compared with six other thio compounds in mice. Arch. Toxicol. 41, 79–88 (1978). https://doi.org/10.1007/BF00351772
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DOI: https://doi.org/10.1007/BF00351772