Chemical Basis for Pharmacological and Therapeutic Actions of Penicillamine

Friedman, Mendel

doi:10.1007/978-1-4757-9113-6_36

Cited by 38 publications

(12 citation statements)

References 61 publications

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“…The actions of DP on connective tissues, including in the lungs, are believed to be mediated through the action of lysyl oxidase, a copper-requiring enzyme active in cross-linking elastin and, to a lesser extent, collagen. DP may also interact with aldehydes to form thiazolidine derivatives, thereby directly affecting collagen crosslinking [Nimni and Bavetta, 1965;Friedman, 1977;Beck et al, 1981;Keen et al, 1983]. DP causes a reduction of maternal plasma copper and zinc, and fetal hepatic zinc and plasma copper in exposed pregnant rats and their fetuses [Keen et al, 1982b.…”

Section: Clinical Reportmentioning

confidence: 96%

Infant with severe penicillamine embryopathy born to a woman with Wilson disease

Pinter

Hogge

McPherson

2004

American J of Med Genetics Pt A

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We report a chromosomally normal infant boy with congenital diffuse cutis laxa, severe micrognathia, contractures of all limbs, and central nervous system abnormalities including agenesis of the corpus callosum, born to a woman taking D-penicillamine (DP) for Wilson disease (WD) throughout her pregnancy. His postnatal course was remarkable for chronic lung disease, profound developmental delays, and probable cortical blindness, as well as resolution of his cutis laxa. Embryopathy is a rare complication in babies born to pregnant women treated with DP, and there have been only seven previous reports of birth defects in exposed infants (three of which had favorable postnatal outcomes). The etiology of the severe outcome in this boy is unclear, but prenatal measurement of maternal copper and zinc levels may be indicated for management.

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Section: Clinical Reportmentioning

confidence: 96%

Infant with severe penicillamine embryopathy born to a woman with Wilson disease

Pinter

Hogge

McPherson

2004

American J of Med Genetics Pt A

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“…Also genetic diagnosis [122] Administration of copper-chelating agents (e.g. penicillamine) [123] Long-Evans Cinnamon rat model [124] Cystic fibrosis Homozygous mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) [125] 1:2500. Approx.…”

Section: Autoimmune Hepatitismentioning

confidence: 99%

Liver fibrosis

Wallace

Burt

Wright

2008

Biochemical Journal

278

272

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Liver damage leads to an inflammatory response and to the activation and proliferation of mesenchymal cell populations within the liver which remodel the extracellular matrix as part of an orchestrated wound-healing response. Chronic damage results in a progressive accumulation of scarring proteins (fibrosis) that, with increasing severity, alters tissue structure and function, leading to cirrhosis and liver failure. Efforts to modulate the fibrogenesis process have focused on understanding the biology of the heterogeneous liver fibroblast populations. The fibroblasts are derived from sources within and out with the liver. Fibroblasts expressing alpha-smooth muscle actin (myofibroblasts) may be derived from the transdifferentiation of quiescent hepatic stellate cells. Other fibroblasts emerge from the portal tracts within the liver. At least a proportion of these cells in diseased liver originate from the bone marrow. In addition, fibrogenic fibroblasts may also be generated through liver epithelial (hepatocyte and biliary epithelial cell)-mesenchymal transition. Whatever their origin, it is clear that fibrogenic fibroblast activity is sensitive to (and may be active in) the cytokine and chemokine profiles of liver-resident leucocytes such as macrophages. They may also be a component driving the regeneration of tissue. Understanding the complex intercellular interactions regulating liver fibrogenesis is of increasing importance in view of predicted increases in chronic liver disease and the current paucity of effective therapies.

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“…D-penicillamine splits disulphide bonds and reacts with aldehyde groups [26]. All three actions would be expected to perturb membrane structure and function and inhibit enzyme activity, and may thereby explain the more deleterious effects of D-penicillamine versus Trien.…”

Section: The Effects O F the Copper Chelators D-penicillamine And Trienmentioning

confidence: 99%

Progressive Atrophy of Pancreatic Acinar Tissue in Rats Fed a Copper-Deficient Diet Supplemented with <i>D</i>-Penicillamine or Triethylene Tetramine: Morphological and Physiological Studies

Smith¹,

Sunter

Case

1982

Digestion

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This paper describes the progressive effects of severe copper depletion on pancreatic weight, structure, amylase content and responses to secretin and caerulein, as well as a number of general body parameters (appearance, body weight and blood indices). Copper depletion was produced by feeding young rats a copper-deficient diet alone or together with either of the two chelating agents D-penicillamine or triethylene tetramine (Trien). After 6 weeks, the copper-deficient diet alone had relatively little effect on general body parameters but reduced gland weight and the secretory response to caerulein. Addition of .D-penicillamine had a deleterious effect on general body parameters; it caused total acinar cell atrophy but left ductal and islet tissue relatively intact; gland weight was markedly reduced, and gland amylase was reduced virtually to zero; and the secretory response to caerulein was almost abolished while that to secretin was reduced. The effects of Trien on general body parameters were less severe; the secretory response to secretin was also less affected, while acinar cell atrophy, gland amylase and the secretory response to caerulein were affected to the same extent as with D-penicillamine. The effects of severe copper depletion on the pancreas were largely irreversible after 13 weeks on a copper-supplemented diet.

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Chemical Basis for Pharmacological and Therapeutic Actions of Penicillamine

Cited by 38 publications

References 61 publications

Infant with severe penicillamine embryopathy born to a woman with Wilson disease

Infant with severe penicillamine embryopathy born to a woman with Wilson disease

Liver fibrosis

Progressive Atrophy of Pancreatic Acinar Tissue in Rats Fed a Copper-Deficient Diet Supplemented with <i>D</i>-Penicillamine or Triethylene Tetramine: Morphological and Physiological Studies

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