Interactions of vitamin E and penicillamine in the treatment of hereditary avian muscular dystrophy.
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.
Serafin
W E
WE
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
Dement
S H
SH
Brandon
S
S
Hill
E J
EJ
Park
C R
CR
Park
J H
JH
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*
D014810:Vitamin E; D003402:Creatine Kinase; D010396:Penicillamine; D024502:alpha-Tocopherol; D024505:Tocopherols