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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.