ZFIN ID: ZDB-PUB-130418-7
Chronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior
Lebold, K.M., Löhr, C.V., Barton, C.L., Miller, G.W., Labut, E.M., Tanguay, R.L., and Traber, M.G.
Date: 2013
Source: Comparative biochemistry and physiology. Toxicology & pharmacology : CBP   157(4): 382-9 (Journal)
Registered Authors: Barton, Carrie, Miller, Galen, Tanguay, Robyn L.
Keywords: alpha-tocopherol, ascorbic acid, ataxia, defined diet, myopathy, neuropathy, vitamin E deficiency symptoms
MeSH Terms:
  • Animals
  • Ascorbic Acid/administration & dosage
  • Ascorbic Acid/analysis
  • Ascorbic Acid/metabolism
  • Ascorbic Acid Deficiency/etiology*
  • Behavior, Animal/physiology*
  • Fibrosis/pathology
  • Half-Life
  • Malondialdehyde/metabolism
  • Muscle, Skeletal/metabolism
  • Muscle, Skeletal/pathology
  • Muscular Diseases/etiology*
  • Necrosis/pathology
  • Oxidative Stress
  • Severity of Illness Index
  • Swimming
  • Vitamin E Deficiency/complications*
  • Zebrafish/metabolism*
  • Zebrafish/physiology
  • alpha-Tocopherol/metabolism
PubMed: 23570751 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.

We hypothesized that zebrafish (Danio rerio) undergoing long-term vitamin E deficiency with marginal vitamin C status would develop myopathy resulting in impaired swimming. Zebrafish were fed for 1 y a defined diet without (E ) and with (E +) vitamin E (500 mg α-tocopherol/kg diet). For the last 150 days, dietary ascorbic acid concentrations were decreased from 3500 to 50 mg/kg diet and the fish sampled periodically to assess ascorbic acid concentrations. The ascorbic acid depletion curves were faster in the E  compared with E + fish (P < 0.0001); the estimated half-life of depletion in the E  fish was 34 days, while in it was 55 days in the E + fish. To assess swimming behavior, zebrafish were monitored individually following a “startle-response” stimulus, using computer and video technology. Muscle histopathology was assessed using hematoxylin and eosin staining on paramedian sections of fixed zebrafish. At study end, E  fish contained 300-fold less α-tocopherol (p < 0.0001), half the ascorbic acid (p = 0.0001) and 3-fold more malondialdehyde (p = 0.0005) than did E + fish. During the first minute following a tap stimulus (p < 0.05), E + fish swam twice as far as did E  fish. In the E  fish, the sluggish behavior was associated with a multifocal, polyphasic, degenerative myopathy of the skeletal muscle. The myopathy severity ranged from scattered acute necrosis to widespread fibrosis and was accompanied by increased anti-hydroxynonenal staining. Thus, vitamin E deficiency in zebrafish causes increased oxidative stress and a secondary depletion of ascorbic acid, resulting in severe damage to muscle tissue and impaired muscle function.