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Protection against Acetaldehyde Toxicity in the rat byl-cysteine, thiamin andl-2-Methylthiazolidine-4-carboxylic acid

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Abstract

Acetaldehyde is 10–30 times more toxic than ethanol and has been implicated in alcoholic cardiomyopathy. Its oral LD50 and LD90 Litchfield-Wilcoxon values were found to be 15.0 (14.4–15.6) mM/kg and 18.0 (15.5–20.5) mM/kg, respectively. Protection against acetaldehyde lethality was obtained by oral intubation of test compounds 30–45 minutes prior to oral intubation of 18 mM/kg of acetaldehyde. At 2.0 mM/kg, survival after 24–72 hours withl-cysteine free base(FB)was80%;withl-2-methylthiazolidine-4-carboxylic acid (l-MTCA), 75%; with thiamin·HCl, 90%; and only 10% with saline control. At 0.3 mM/kg, thiamin·HCl gave virtually no protection (13% survival). The combination ofl-cysteine FB plus thiamin·HCl, each at 2.0 mM/kg, gave 100% survival. The oral LD50 dose (Litchfield-Wilcoxon) in mM/kg forl-cysteine FB was 15.6(14.8–16.4); forl-MTCA, 17.9 (17.0–18.8), and for thiamin·HCl, 11.0 (10.4–11.6). The ratio of toxic dose-protective dose of the first two compounds warrants further study of them in combination with thiamin as possible protective agents against the chronic toxicity of acetaldehyde associated with heavy ethanol intake and heavy smoking.

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References

  1. J. P. von Wartburg,The Metabolism of Alcohol in Normals and Alcoholics: Enzymes, in:The Biology of Alcoholism, Vol. 1 (Eds B. Kissin and H. Begleiter; Plenum Press, New York 1971), p. 63–102.

    Google Scholar 

  2. J.R. Newsome, V. Norman andC.H. Keith,Vapor Phase Analysis of Cigarette Smoke, Tob. Sci.9, 102–110 (1965).

    Google Scholar 

  3. J. Akabane,Aldehydes and Related Compounds, in:International Encyclopedia of Pharmacology and Therapeutics, Vol. II (Ed. J. Trémolières; Pergamon Press, New York 1970), p. 523–560.

    Google Scholar 

  4. E.B. Truitt, Jr., andM.J. Walsh,The Role of Acetaldehyde in the Actions of Ethanol, in:The Biology of Alcoholism, Vol. 1 (Eds B. Kissin and H. Begleiter; Plenum Press, New York 1971), p. 161–195.

    Google Scholar 

  5. E. W. Martin,Hazards of Medication (J. B. Lippincott Co., Philadelphia 1972), p. 430–439.

    Google Scholar 

  6. H.T.P. Ammon, C.-J. Estler andF. Heim Inactivation of Coenzyme A by Ethanol-I: Acetaldehyde as Mediator of the Inactivation of Coenzyme A Following the Administration of Ethanol in vivo, Biochem. Pharmac.18, 29–33 (1969).

    Article  Google Scholar 

  7. T.N. James andE.S. Bear,Effects of Ethanol and Acetaldehyde on the Heart, Am. Heart J.74, 243–255 (1967).

    Article  PubMed  Google Scholar 

  8. T.N. James andE.S. Bear,Cardiac Effects of Some Simple Aliphatic aldehydes, J. Pharmac. exp. Ther.163, 300–308 (1968).

    Google Scholar 

  9. J.L. Egle, Jr. Effects of Inhaled Acetaldehyde and Propionaldehyde on Blood Pressure and Heart Rate, Toxic. appl. Pharmac.23, 131–135 (1972).

    Article  Google Scholar 

  10. M.P. Schubert,Reactions of Semimercaptols with Amino Compounds, J. Biol. Chem.121, 539–548 (1937).

    Google Scholar 

  11. H.J. Debey, J.B. Mackenzie andC.G. Mackenzie,The Replacement by Thiazolidinecarboxylic Acid of Exogenous Cystine and Cysteine, J. Nutr.66, 607–619 (1958).

    PubMed  Google Scholar 

  12. R. E. Olson,nutrition and Alcoholism, in:Modern Nutrition in Health and Disease (Eds M. G. Wohl and R. S. Goodhart; Lea and Febiger 1968), p. 767–781.

  13. K. P. Dubois, L. W. Holm yndW. L. Doyle,Biochemical Changes Following Poisoning of Rats by Alpha-Naphthylthiourea, Proc. Soc. Exp. Biol. Med.61, 102–104 (1946).

    Google Scholar 

  14. J. B. Mackenzie andC. G. Mackenzie,Production of Pulmonary Edema by Thiourea in the Rat, and Its Relation to Age, Proc. Soc. Exp. Biol. Med.54, 34–37 (1943).

    Google Scholar 

  15. J. T. Litchfield andF. Wilcoxon,A Simplified Method for Evaluating Dose-Effect Experiments, J. Pharmac. exp. Ther.96, 99–113 (1949).

    Google Scholar 

  16. G. A. Condouris,The Natural Laws Concerning the Use of Drugs in Man and Animals, in:Drill's Pharmacology in Medicine, 3rd ed. (Ed. J. R. DiPalma; McGraw-Hill, New York 1965), p. 12.

    Google Scholar 

  17. D.L.J. Bilbey, H. Salem andM.H. Grossman,The Anatomical Basis of the Straub Phenomenon, Br. J. Pharmac.15, 540–543 (1960).

    Google Scholar 

  18. H. Molitor,Vitamins as Pharmacological Agents, Fed. Proc.1, 309–315 (1942).

    Google Scholar 

  19. G.W. Phillips, E.B. Carmichael andF.A. Kay,Studies on Paraldehyde. II. The Median Lethal Dose, LD50, of Paraldehyde for Both Young and Old Rats on Two Dietary Regimes, Anesthesiology5, 287–290 (1944).

    Google Scholar 

  20. H.F. Smyth, Jr., C.P. Carpenter andC.S. Weil,Range-Finding Toxicity Data: List IV, AMA Archiv. Indust. Hyg. Occup. Med.4, 119–122 (1951).

    Google Scholar 

  21. P.D. Boyer,Sulfhydryl and Disulfide Groups of Enzymes, in:The Enzymes, Vol. 1 (Eds P. D. Boyer, H. Lardy and K. Myrback; Academic Press, New York 1959), p. 511–588.

    Google Scholar 

  22. M.P. Schubert,Compounds of Thiol Acids with Aldehydes, J. Biol. Chem. 114, 341–350 (1936).

    Google Scholar 

  23. R. M. Macleod, I. Fridovich andP. Handler Influence of Sulfhydryl Compounds on the Equilibrium of the Alcohol Dehydrogenase Reaction, Archiv. Biochem. Biophysics72, 239–241 (1957).

    Article  Google Scholar 

  24. F. R. Bertrand,2-Methylthiazolidine-4-Carboxylic Acid as Cough Inhibitor (Patent) (Sogespar, S.A.) Ger. Offen. 1,965,343 (Cl. C 07d), 23 July 1970, Fr. Appl. 31 Dec. 1968 (See Chem. Abst.73, 374, Abst. No. 77242V [1970].

  25. J. E. Maines III andE. E. Aldinger,Myocardial Depression Accompanying Chronic Consumption of Alcohol, Am. Heart J.73, 55–63 (1967).

    Article  PubMed  Google Scholar 

  26. C. S. Alexander,The Concept of Alcoholic Myocardiopathy, Med. Clin. No. America52, No. 5, 1183–1191 (1968).

    Google Scholar 

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Supported by US Veterans Administration (Project Nos. 8078-01 and [8078] 2-70)

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Sprince, H., Parker, C.M., Smith, G.G. et al. Protection against Acetaldehyde Toxicity in the rat byl-cysteine, thiamin andl-2-Methylthiazolidine-4-carboxylic acid. Agents and Actions 4, 125–130 (1974). https://doi.org/10.1007/BF01966822

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