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Chronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior

Lebold, Katie M., Löhr, Christiane V., Barton, Carrie L., Miller, Galen W., Labut, Edwin M., Tanguay, Robert L., Traber, Maret G.
Comparative Biochemistry and Physiology, Part C 2013 v.157 pp. 382-389
Danio rerio, alpha-tocopherol, ascorbic acid, ascorbic acid deficiency, computers, diet, fibrosis, fish, half life, histopathology, malondialdehyde, muscles, muscular diseases, necrosis, oxidative stress, skeletal muscle, swimming, vitamin E deficiency, vitamin status
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 (500mg α-tocopherol/kg diet). For the last 150days, dietary ascorbic acid concentrations were decreased from 3500 to 50mg/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 34days, while in it was 55days 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.