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2330. Rapeseed: toxic offenders traced?
NATURAL PRODUCTS
279
alkaloid, include necrotic and vascular changes, cirrhosis, fibrosis, formation of megalocytes (by the enlargement of parenchymal cells failing to undergo full cell division) and possibly neoplasia (ibid 1971, 9, 894). The paper cited above reports a study on the influence of various factors on the toxicity of lasiocarpine and on its effect on liver-cell division. Diets moderately or severely deficient in lipotropes fed to rats for 6 wk prior to lasiocarpine treatment markedly reduced the lethality and necrotizing effect of a single oral dose of 110 or 150 mg lasiocarpine/kg, when compared with adequate diets. Mercaptoethylamine (300 mg/kg given orally) dosed simultaneously with lasiocarpine (110 mg/kg) also reduced lasiocarpine toxicity in rats on the lipotrope-adequate diets, but no antagonism was seen when mercaptoethylamine was given 4 hr before or 24 hr after lasiocarpine or when ct-tocopherol or ubiquinone were given in oral doses of 300 mg/kg at --4, 0 or 24 hr after lasiocarpine. In another experiment, rats were fed a lipotrope-deficient or lipotrope-adequate diet for 2 wk before receiving a single oral dose of 5-100 mg lasiocarpine/kg or three 40-mg/kg doses on alternate days. Rats were subjected to partial (two-thirds) hepatectomy 2 wk or 4 or 6 months after treatment, and DNA synthesis and mitosis were determined in the livers at 1 or 2 days or 2 months after surgery. In general the inhibition of cell division and DNA synthesis by lasiocarpine was not suppressed by the lipotrope-deficient diet, nor by mercaptoethylamine given in three 300-mg/kg doses simultaneously with lasiocarpine. Since the mitotic inhibition induced by lasiocarpine persisted for over 4 months, attempts were made to use lasiocarpine to retard the development of hyperplasia and possibly neoplasia induced by the known liver carcinogen, N-2-fluorenylacetamide (AAF), Rats received three doses of 40 mg lasiocarpine/kg on alternate days immediately before the dietary administration of 0.0125 ~o AAF, which was continued for 11 wk, during which some of the rats received two further doses of lasiocarpine. The animals were killed at 1, 15 or 23 wk after AAF- feeding ceased. Lasiocarpine failed to arrest the development of precancerous or cancerous lesions in the liver associated with AAF and, if anything, enhanced AAF hepatocarcinogenesis. Lipotrope-deficient diets were found to inhibit processing-enzyme induction in rat-liver microsomes. If this inhibition suppresses the formation of toxic pyrroles from lasiocarpine, this could account for the diet's antagonism to lasiocarpine-induced necrosis. The inability of this diet or of mercaptoethylamine to suppress the mitotic inhibition of lasiocarpine indicates that cell division was inhibited either by the parent compound or by a metabolite other than the one causing necrosis.
2330. Rapeseed: Toxic offenders traced? Oliver, S. L., McDonald, B. E. & Opuszyfiska, T. (1971). Weight gain, protein utilization, and liver histochemistry of rats fed low- and high-thioglucoside-content rapeseed meals. Can. J. Physiol. Pharmac. 49, 448. Nera, E. A., Beare-Rogers, J. L. & Heggtveit, H. A. (1971). Cardiotoxicity of rapeseed oil. Am. J. Path. 62, 34a. The impairment of growth and feed efficiency in animals consuming rapeseed meal has been attributed to the presence of goitrogens and tannins. Thyroid enlargement also results from the feeding of rapeseed meal. In order to establish the importance of the thioglucoside content in the toxicity of rapeseed meal, rats were fed diets containing 36 or 44 ~o rapeseed
280
NATURAL PRODUCTS
meal with a low (LTG) or high thioglucoside (HTG) content respectively (80 ppm oxazolidinethione plus isothiocyanate or 4200 ppm) or 19yo casein as the sole protein source (Oliver et al. cited above). Both rapeseed meals contained just over 2,5 ~o tannins. After the various diets had been fed for up to I0 wk, it was found that the HTG diet caused poor growth, a reduction in nitrogen retention and food intake, enlargement of the thyroid and to a lesser extent of the liver, kidneys, adrenals and testes, and histochemical changes in acid and alkaline phosphatases and adenosine triphosphatase of the liver, when compared with the casein and LTG diets. Fat infiltration into the liver was seen with both the HTG and LTG diets. Thus the deleterious effects observed with rapeseed meal would appear to be primarily due to the HTG content. The second paper cited (presented in abstract form) describes a study in which rats were fed diets containing 5, I0 or 20 ~ rapeseed oil and changes in the myocardium were followed for up to 20 wk. Myocardiotoxicity, characterized by severe fatty degeneration progressing to multiple foci of myocytolysis, overt necrosis and fibrosis, was associated with the 10 and 20 ~o levels, especially the latter. The level of erucic acid (known to account for almost half the total fatty acids of rapeseed oil) in cardiac fatty acids increased with increasing levels of rapeseed oil in the diet. Erucic acid appears to a be significant factor in the myocardiopathy and it is probable that carbon chain length and degree of saturation of fatty acids are important in determining their relative cardiotoxicity. Similar myocardial lesions were seen with fish oils and in view of the widespread use of rapeseed oil and fish oils in foodstuffs the potential hazard to man needs to be evaluated.
2331. Allergic reactions to soya-bean products Fries, J. H. (1971). Studies on the allergenicity of soy bean. Ann. Allergy 29, 1. Referring to the increasing incidence of allergic reactions to legumes and to the possible association of this with the ever-widening use of soya-bean products and particularly with the feeding of soya-bean milk in infancy, the author cited above suggests that a significant section of the population may be being inadvertently sensitized to a large group of plants of nutritional importance. The study reported was carried out on 30 children (aged 3-15 yr) all of whom suffered from an atopic allergenicity and were subject to severe allergic symptoms of the respiratory type. About half of the group showed marked clinical reactions to one or more foods. Legumes were involved most frequently, but clinical reactions to eggs, shellfish and potatoes were also demonstrated. In several instances, inhalation of the offending substance produced symptoms. Half the group had been fed soya-bean milk in infancy; the remainder had no known exposure to soya-bean products. Twelve of those who had been fed soya-bean milk previously, as well as all the rest of the group, gave a positive intracutaneous test reaction to soya-bean extracts as well as to one or more of the other legumes tested (peanut, green pea, lima bean, string bean). The three who did not develop a positive skin reaction to soya bean gave a positive reaction to two other legumes. There was close correlation between clinical and cutaneous sensitivity. It is commonly assumed that soya-bean milk is hypoallergenic (Cited in F.C.T. 1967, 5, 441), but the results of a further series of tests reported in this paper demonstrate that sensitivity does occur. Almost all of the soyabean-sensitive children in the group described above gave a positive reaction to cutaneous tests with soya-milk extracts. Although the commonly reported clinical reactions to soya-bean milk were diarrhoea, vomiting and nausea, which
279
alkaloid, include necrotic and vascular changes, cirrhosis, fibrosis, formation of megalocytes (by the enlargement of parenchymal cells failing to undergo full cell division) and possibly neoplasia (ibid 1971, 9, 894). The paper cited above reports a study on the influence of various factors on the toxicity of lasiocarpine and on its effect on liver-cell division. Diets moderately or severely deficient in lipotropes fed to rats for 6 wk prior to lasiocarpine treatment markedly reduced the lethality and necrotizing effect of a single oral dose of 110 or 150 mg lasiocarpine/kg, when compared with adequate diets. Mercaptoethylamine (300 mg/kg given orally) dosed simultaneously with lasiocarpine (110 mg/kg) also reduced lasiocarpine toxicity in rats on the lipotrope-adequate diets, but no antagonism was seen when mercaptoethylamine was given 4 hr before or 24 hr after lasiocarpine or when ct-tocopherol or ubiquinone were given in oral doses of 300 mg/kg at --4, 0 or 24 hr after lasiocarpine. In another experiment, rats were fed a lipotrope-deficient or lipotrope-adequate diet for 2 wk before receiving a single oral dose of 5-100 mg lasiocarpine/kg or three 40-mg/kg doses on alternate days. Rats were subjected to partial (two-thirds) hepatectomy 2 wk or 4 or 6 months after treatment, and DNA synthesis and mitosis were determined in the livers at 1 or 2 days or 2 months after surgery. In general the inhibition of cell division and DNA synthesis by lasiocarpine was not suppressed by the lipotrope-deficient diet, nor by mercaptoethylamine given in three 300-mg/kg doses simultaneously with lasiocarpine. Since the mitotic inhibition induced by lasiocarpine persisted for over 4 months, attempts were made to use lasiocarpine to retard the development of hyperplasia and possibly neoplasia induced by the known liver carcinogen, N-2-fluorenylacetamide (AAF), Rats received three doses of 40 mg lasiocarpine/kg on alternate days immediately before the dietary administration of 0.0125 ~o AAF, which was continued for 11 wk, during which some of the rats received two further doses of lasiocarpine. The animals were killed at 1, 15 or 23 wk after AAF- feeding ceased. Lasiocarpine failed to arrest the development of precancerous or cancerous lesions in the liver associated with AAF and, if anything, enhanced AAF hepatocarcinogenesis. Lipotrope-deficient diets were found to inhibit processing-enzyme induction in rat-liver microsomes. If this inhibition suppresses the formation of toxic pyrroles from lasiocarpine, this could account for the diet's antagonism to lasiocarpine-induced necrosis. The inability of this diet or of mercaptoethylamine to suppress the mitotic inhibition of lasiocarpine indicates that cell division was inhibited either by the parent compound or by a metabolite other than the one causing necrosis.
2330. Rapeseed: Toxic offenders traced? Oliver, S. L., McDonald, B. E. & Opuszyfiska, T. (1971). Weight gain, protein utilization, and liver histochemistry of rats fed low- and high-thioglucoside-content rapeseed meals. Can. J. Physiol. Pharmac. 49, 448. Nera, E. A., Beare-Rogers, J. L. & Heggtveit, H. A. (1971). Cardiotoxicity of rapeseed oil. Am. J. Path. 62, 34a. The impairment of growth and feed efficiency in animals consuming rapeseed meal has been attributed to the presence of goitrogens and tannins. Thyroid enlargement also results from the feeding of rapeseed meal. In order to establish the importance of the thioglucoside content in the toxicity of rapeseed meal, rats were fed diets containing 36 or 44 ~o rapeseed
280
NATURAL PRODUCTS
meal with a low (LTG) or high thioglucoside (HTG) content respectively (80 ppm oxazolidinethione plus isothiocyanate or 4200 ppm) or 19yo casein as the sole protein source (Oliver et al. cited above). Both rapeseed meals contained just over 2,5 ~o tannins. After the various diets had been fed for up to I0 wk, it was found that the HTG diet caused poor growth, a reduction in nitrogen retention and food intake, enlargement of the thyroid and to a lesser extent of the liver, kidneys, adrenals and testes, and histochemical changes in acid and alkaline phosphatases and adenosine triphosphatase of the liver, when compared with the casein and LTG diets. Fat infiltration into the liver was seen with both the HTG and LTG diets. Thus the deleterious effects observed with rapeseed meal would appear to be primarily due to the HTG content. The second paper cited (presented in abstract form) describes a study in which rats were fed diets containing 5, I0 or 20 ~ rapeseed oil and changes in the myocardium were followed for up to 20 wk. Myocardiotoxicity, characterized by severe fatty degeneration progressing to multiple foci of myocytolysis, overt necrosis and fibrosis, was associated with the 10 and 20 ~o levels, especially the latter. The level of erucic acid (known to account for almost half the total fatty acids of rapeseed oil) in cardiac fatty acids increased with increasing levels of rapeseed oil in the diet. Erucic acid appears to a be significant factor in the myocardiopathy and it is probable that carbon chain length and degree of saturation of fatty acids are important in determining their relative cardiotoxicity. Similar myocardial lesions were seen with fish oils and in view of the widespread use of rapeseed oil and fish oils in foodstuffs the potential hazard to man needs to be evaluated.
2331. Allergic reactions to soya-bean products Fries, J. H. (1971). Studies on the allergenicity of soy bean. Ann. Allergy 29, 1. Referring to the increasing incidence of allergic reactions to legumes and to the possible association of this with the ever-widening use of soya-bean products and particularly with the feeding of soya-bean milk in infancy, the author cited above suggests that a significant section of the population may be being inadvertently sensitized to a large group of plants of nutritional importance. The study reported was carried out on 30 children (aged 3-15 yr) all of whom suffered from an atopic allergenicity and were subject to severe allergic symptoms of the respiratory type. About half of the group showed marked clinical reactions to one or more foods. Legumes were involved most frequently, but clinical reactions to eggs, shellfish and potatoes were also demonstrated. In several instances, inhalation of the offending substance produced symptoms. Half the group had been fed soya-bean milk in infancy; the remainder had no known exposure to soya-bean products. Twelve of those who had been fed soya-bean milk previously, as well as all the rest of the group, gave a positive intracutaneous test reaction to soya-bean extracts as well as to one or more of the other legumes tested (peanut, green pea, lima bean, string bean). The three who did not develop a positive skin reaction to soya bean gave a positive reaction to two other legumes. There was close correlation between clinical and cutaneous sensitivity. It is commonly assumed that soya-bean milk is hypoallergenic (Cited in F.C.T. 1967, 5, 441), but the results of a further series of tests reported in this paper demonstrate that sensitivity does occur. Almost all of the soyabean-sensitive children in the group described above gave a positive reaction to cutaneous tests with soya-milk extracts. Although the commonly reported clinical reactions to soya-bean milk were diarrhoea, vomiting and nausea, which