Encephalomalacia in chicks

There is no doubt that as dietary agents tocopherol and Factor 3/selenium arc different, independent entities (Schwarz, 1960). In principle, one must separate clearly three groups of diseases those caused purely by vitamin E deficiency, which are not influenced by Factor 3/selenium even in large excess (resorption sterility in rats, encephalomalacia in chicks) those... 

In 11)31, Pappenheimer and Goettsch published the first description of a newly discovered disease, which was called nutritional encephaloTnalaeia. Although the diet recommended by Pappenheimer and Goettsch for producing encephalomalacia in chicks contained some 20% lard and about 2 % cod liver oil, it was sometime later that the role of the dietary fats was evaluated. The composition of this diet is shown in Table I. 

At least one vitamin E deficiency sign is known to occur only when a certain class of polyunsaturated fatty acids is furnished in the diet. For instance, encephalomalacia in chicks appears when the diet contains linoleic or arachidonic acid, but not when the diet is fat free or contains linolenic acid. It is possible that encephalomalacia is due to the lack of an antioxidant effect, but attempts to demonstrate autoxidation products in the affected tissue have not been successful. 

These results suggest that the presence in the diet of unsaturated fats increase tocopherol requirements to 10 to 100 times the amounts required in their absence. In the prevention of encephalomalacia in chicks it appears that the role of tocopherol is to act as an antioxidant specifically related to linoleic acid metabolism (Scott, 1962). Whether such specificity of action can explain the results obtained with ruminants seems doubtful, in view of the low linoleic acid content of highly unsaturated fraction of cod liver oil. 

Pure fatty acid hydroperoxides are very toxic to experimental animals when administered intravenously (i.v.) but not oraUy (Horgan et al., 1957 Olcott and Dolev, 1963 Findlay et al., 1970). Cortesi and Privett (1972) have shown that the 24-h lethal i.v. dose of a high purity preparation of methyl linoleate hydroperoxides in adult male rats was approximately 0.07 mmol/100 g body weight, and that the major effect of injected linoleate hydroperoxides was on the lungs. Also, vitamin E deficiency symptoms such as encephalomalacia in chicks (Nishida et al., 1960), and creatinuria and erythrocyte hemolysis in rabbits (Kokatnur et al., 1966) have been observed in animals infused with methyl linoleate hydroperoxides. 

Besides encephalomalacia and exudative diathesis, a third easily observable sign of vitamin E deficiency may be seen in chicks, viz., a form... 

The. animal work will be described only sufficiently to allow the reader to appreciate lietter the discussion of the human studies. When it became apparent in 19.55 that the peroxide hemolysis test was dependent not only on the tocopherol level of the blood but also upon the level of linoleic acid (and other autoxidizable components) in the stroma of the erythrocyte, animal experiments were designed to obtain more exact correlations between tocopherol needs and linoleic acid intake. This relationship between linoleic acid content of the diet and the incidence of chick encephalomalacia (Century and Horwitt, 19.58) was not recorded until later (Century et al., 19.59 Century and Horwitt, 19.59) when observation of cerebellar encephalomalacia in an infant that had been fed a commercial cottonseed oil preparation intravenously came to our attention (Horwitt and Bailey, 1959). In the meantime, there had been a number of reports to certify the relationship between linoleic acid consumption and chick encephalomalacia (Dam et al, 19.58 Machlin and Gordon, 1960). With the advent of better gas chromatographic techniques, it was soon possible to show that the linoleic acid content of the cerebellum was diet dependent (Horwitt et al., 1959 Witting et al., 1961). The marked effects of diet on the fatty acids of the mitochondria of chick brains has also been reported (Horwitt, 1981a). The levels of linoleic acid are much lower in brain tissues than in any tissue analyzed to date and this relatively low linoleic acid level may be considered a characteristic of brain tissue. The significance of this difference is not known. It is of interest to note that the current interpretations of the effect of more unsaturated fats on the production of chick encephalomalacia were anticipated by Dam in 1944. 

Vitamin E deficiency in chicks may lead to a munber of distinct diseases myopathy, encephalomalacia and exudative diathesis. In nutritional myopathy the main muscles affected are the pectorals, although the leg muscles also may be involved. Nutritional encephalomalacia, or crazy chick disease , is a condition in which the chick is imable to walk or stand and is accompanied by haemorrhages and necrosis of brain cells. Exudative diathesis is a vascular disease of chicks characterised by a generahsed oedema of the subcutaneous fatty tissues, associated with an abnormal permeabUity of the capUlary walls. Both selenium and vitamin E appear to be involved in nutritional myopathy and in exudative diathesis, but the element does not seem to be important in nutritional encephalomacia. It should be stressed that sele-niiun itself is a very toxic element and care is required in its use as a dietary additive. The toxic natine of seleniiun is discussed in Chapter 7. 

In growing chicks, a deficiency can result in (i) encephalomalacia or crazy chick disease (ii) exudative diathesis, an oedema caused by excessive capillary permeability or (iii) muscular dystrophy. Encephalomalacia occurs when the diet contains unsaturated fats that are susceptible to rancidity. Some antioxidants, in addition to vitamin E, are also effective against encephalomalacia. Exudative diathesis is prevented by dietary selenium, and muscular dystrophy is a complex disease influenced by vitamin E, selenium, and the... 

Vitamin E-deficiency diseases are well known among laboratory and farm animals and can be a considerable problem in animal husbandry. Thus, the vitamin was discovered because its absence from the diet causes pregnant female rats to resorb their foetuses [25], and male rats to suffer testicular degeneration [26]. In the rabbit muscular dystrophy occurs, and in sheep and cattle similar muscular degeneration also is the principle sign of vitamin E deficiency [27], In the chick given high levels of linoleic acid and no vitamin E an acute central nervous system lesion called encephalomalacia occurs... 

Encephalomalacia occurred only in a few cases when Torula yeast diets that furnished about the same amount of linoleic acid as the casein diets with 30% lard were fed. When selenium was added to the Torula yeast diets, the chicks lived longer and a few more cases of encephalomalacia appeared. 

The hypothesis that autoxidation occurring in the brain is the cause of encephalomalacia seems obvious, but meets the following difficulties (1) as already mentioned, peroxides have never been detected in the brain of chicks with encephalomalacia (2) the brain of chicks is extremely low in vitamin E, even when this vitamin is supplied through the diet. 

Although some similarities are observed in the tissues of chicks suffering from these diseases, it appears that no common metabolic defect can be held responsible for all three conditions, since various specific dietary changes unrelated to the vitamin E content of the diet can completely prevent one of the diseases without having any effect upon the other two. The most important of these are the prevention of encephalomalacia with synthetic antioxidants, the effectiveness of inorganic selenium in prevention of exudative diathesis, and the role of cystine in preventing muscular dystrophy. 

Basal diet deficient in vitamin E contained approximately one-half the chick s requirement of methionine (0.2%), one-fifth the chick s requirement of cystine (0.05%). Ethoxyquin was added at level of 0.0125%, which prevented encephalomalacia sodium selenite at a level to provide 0.1 ppm of selenium prevented exudative diathesis. 

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