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. 1975 Oct;56(4):842–849. doi: 10.1172/JCI108163

Beneficial effects of penicillamine treatment on hereditary avian muscular dystrophy.

T Chou, E J Hill, E Bartle, K Woolley, V LeQuire, W Olson, R Roelofs, J H Park
PMCID: PMC301939  PMID: 1159090

Abstract

Hereditary muscular dystrophy in chickens of the New Hampshire strain was treated with penicillamine from the 9th day after hatching to the 425th day. The adult maintenance dose for males was 50 mg/kg per day and for females, 13-65 mg/kg per day. In avian dystrophy, deterioration of the muscle fibers is evidenced in the 2nd mo by an inability of the birds to rise after falling on their backs and by a progressive rigidity of the wings. The drug delayed the onset of symptoms and partially alleviated the debilitating aspects of the disease. Penicillamine produced three major improvements: (a) better righting ability when birds were placed on their backs; (b) greater wing flexibility; (c) and suppression of plasma creatine phosphokinase activity. The results are statistically analyzed and discussed in relationship to Duchenne dystrophy. Normal birds were not affected by penicillamine as judged by these parameters. The rationale for using penicillamine, a sulfhydryl compound with reducing properties, was (a) to attempt to protect essential thiol enzymes in the anabolic and glycolytic pathways against inactivation and (b) to prevent collagen cross-linking and deposition in muscle. Although the precise mechanism of drug action has not been determined. the possible role of penicillamine in mitigating the symptoms of genetic dystrophy in man is under consideration. Further, penicillamine may have a more generalized application i the prevention of contractures in a variety of neuromuscular disorders.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. APOSHIAN H. V., BRADHAM L. S. Metabolism in vitro of the sulphydryl amino acids, L- and D-penicillamine. Biochem Pharmacol. 1959 Dec;3:38–41. doi: 10.1016/0006-2952(59)90006-1. [DOI] [PubMed] [Google Scholar]
  2. Chvapil M., Ryan J. N., Brada Z. Effects of selected chelating agents and metals on the stability of liver lysosomes. Biochem Pharmacol. 1972 Apr 15;21(8):1097–1105. doi: 10.1016/0006-2952(72)90103-7. [DOI] [PubMed] [Google Scholar]
  3. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  4. Farrell P. M., Eyerman E. L., Tureen L. L. Comparison of plasma creatine phosphokinase changes in nutritional and genetic muscular dystrophy in the chicken. Ann N Y Acad Sci. 1966 Sep 9;138(1):102–112. doi: 10.1111/j.1749-6632.1966.tb41159.x. [DOI] [PubMed] [Google Scholar]
  5. HOFFSTEN P. E., HUNTER F. E., Jr, GEBICKI J. M., WEINSTEIN J. Formation of "lipid peroxide" under conditions which lead to swelling and lysis of rat liver mitochondria. Biochem Biophys Res Commun. 1962 May 4;7:276–280. doi: 10.1016/0006-291x(62)90190-0. [DOI] [PubMed] [Google Scholar]
  6. Kosower E. M., Werman R. New step in transmitter release at the myoneural junction. Nat New Biol. 1971 Sep 22;233(38):121–123. doi: 10.1038/newbio233121a0. [DOI] [PubMed] [Google Scholar]
  7. Lorber A., Chang C. C., Masuoka D., Meacham I. Effect of thiols in biological systems on protein sulfhydryl content. Biochem Pharmacol. 1970 May;19(5):1551–1560. doi: 10.1016/0006-2952(70)90143-7. [DOI] [PubMed] [Google Scholar]
  8. MAHOWALD T. A., NOLTMANN E. A., KUBY S. A. Studies on adenosine triphosphate transphosphorylases. III. Inhibition reactions. J Biol Chem. 1962 May;237:1535–1548. [PubMed] [Google Scholar]
  9. Nimni M. E. A defect in the intramolecular and intermolecular cross-linking of collagen caused by penicillamine. I. Metabolic and functional abnormalities in soft tissues. J Biol Chem. 1968 Apr 10;243(7):1457–1466. [PubMed] [Google Scholar]
  10. Nimni M. E., Deshmukh K., Gerth N., Bavetta L. A. Changes in collagen metabolism associated with the administration of penicillamine and various amino and thiol compounds. Biochem Pharmacol. 1969 Apr;18(4):707–714. doi: 10.1016/0006-2952(69)90041-0. [DOI] [PubMed] [Google Scholar]
  11. Werman R., Carlen P. L., Kushnir M., Kosower E. M. Effect of the thiol-oxidizing agent, diamide, on acetylcholine release at the frog endplate. Nat New Biol. 1971 Sep 22;233(38):120–121. doi: 10.1038/newbio233120a0. [DOI] [PubMed] [Google Scholar]
  12. Wills E. D., Wilkinson A. E. Release of enzymes from lysosomes by irradiation and the relation of lipid peroxide formation to enzyme release. Biochem J. 1966 Jun;99(3):657–666. doi: 10.1042/bj0990657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wills E. D., Wilkinson A. E. The effect of irradiation on sub-cellular particles--destruction of sulphydryl groups. Int J Radiat Biol Relat Stud Phys Chem Med. 1967;13(1):45–55. doi: 10.1080/09553006714551311. [DOI] [PubMed] [Google Scholar]
  14. Yu M. K., Wright T. L., Dettbarn W. D., Olson W. H. Pargyline-induced myopathy with histochemical characteristics of Duchenne muscular dystrophy. Neurology. 1974 Mar;24(3):237–244. doi: 10.1212/wnl.24.3.237. [DOI] [PubMed] [Google Scholar]
  15. ZALKIN H., TAPPEL A. L., CALDWELL K. A., SHIBKO S., DESAI I. D., HOLLIDAY T. A. Increased lysosomal enzymes in muscular dystrophy of vitamin E-deficient rabbits. J Biol Chem. 1962 Aug;237:2678–2682. [PubMed] [Google Scholar]

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