title: Interactions of vitamin E and penicillamine in the treatment of hereditary avian muscular dystrophy.
abstract: Our prior work demonstrated that penicillamine treatment of dystrophic chickens delayed the onset of symptoms, partially alleviated contractures, improved muscle function, and lowered serum creatine kinase. Penicillamine, a sulfhydryl compound with reducing properties, also prevented inactivation of glycolytic enzymes by protecting thiol groups. The present study shows that vitamin E enhances the therapeutic effects of penicillamine. Interaction of these two reductants is dose related. With vitamin E as adjunct therapy, the dosage level of penicillamine could be lowered by 50%, thereby minimizing side effects. The therapeutic rationale for two antioxidants is that penicillamine may act primarily in the cytoplasm to prevent oxidative damage, whereas the more hydrophobic vitamin E may protect membrane bilayers. Additionally, penicillamine may prevent collagen cross-linking and, deposition of insoluble collagen in muscle and thus decrease contracture formation. General applications of combined penicillamine and vitamin E therapy are discussed regarding prevention of free radical and oxidative damage in Duchenne dystrophy and a wide range of human diseases.
authors: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors: W E
authors: WE
authors: Serafin
authors: S H
authors: SH
authors: Dement
authors: S
authors: S
authors: Brandon
authors: E J
authors: EJ
authors: Hill
authors: C R
authors: CR
authors: Park
authors: J H
authors: JH
authors: Park
mesh_terms: D000818:Animals; D002645:Chickens; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D009048:Motor Skills / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000201:enzymology; D010396:Penicillamine / Q000627:therapeutic use*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
chemical_list: D014810:Vitamin E; D003402:Creatine Kinase; D010396:Penicillamine; D024502:alpha-Tocopherol; D024505:Tocopherols