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1027. Pancreatic lesions by a methionine derivative
244
NATURAL PRODUCTS
Cited in F.C.T. 1964, 2, 282) and 3,4-benzopyrene, traces of which are produced during roasting (ibid 1964, 2, 384). In addition, raw coffee oil (I) causes decreased growth and protein efficiency and liver enlargement in rats (ibm 1965, 3, 358) and this work has now been extended to an investigation of the toxicity of cafestol (II), a diterpene constituent of I. Up to 1.25 % of II, either in the free form or conjugated as a fatty acid monoester, is present in I. The toxicity of II was determined by the chick embryo test (ibid 1964, 2, 287; Fd Cosmet. Toxicol. 1964, 2, 717). Being insoluble in aqueous solutions, II was injected into the yolk sac of 6-day incubated eggs in 0.05 or 0.1 ml olive oil. Since olive oil itself was found to possess some toxicity (an LD50 of 9-94 ml or 9.11 g/kg egg weight), the LD5o of II had to be calculated and was found to be 4-15 mg/kg egg weight. Although II is quite toxic to the chick embryo, it does not necessarily follow that it is also harmful to mammals. This study emphasizes the necessity of taking into account the toxicity of the solvent in this type of test. 1026. No monkey nuts for crotalaria
Allen, J. R., Carstens, L. A. & Knezevic, A. L. (1965). Crotalaria spectabilis intoxication in Rhesus monkeys. Am. J. vet. Res. 26, 753. The vegetation and seeds of Crotalaria spectabilis (I) are toxic to most animals and to man, the toxic principle being the alkaloid monocrotaline. Details have already been given of the toxic effects of seeds of I to poultry (Cited in F.C.T. 1964, 2, 122). The liver appears to be the main site of attack in animals as well as in man and the present study shows that the monkey is no exception. Feeding diets containing 0.25-1.0% seeds of I to monkeys resulted in a loss in body weight and death within 162-263 days. Severe ascites, hydrothorax and subcutaneous oedema were manifest at autopsy. Fluid accumulation was attributed to severe liver injury with a consequent level of albumin synthesis inadequate to maintain the osmotic pressure of the blood, as reflected by a marked shift in the serum albumin/globulin ratio. Liver damage was extensive and consisted of vacuolar degeneration and haemorrhagic necrosis. The resulting distortion of liver architecture caused blockage of several bile canaliculi which contributed to a slight rise in serum bilirubin. Pulmonary oedema and haemorrhage were also found. 1027. Pancreatic lesions by a methionine derivative
Alvizouri, M., Vazquez, H., Macouzet, J. & Cortes, J. (1965). Pancreatic lesions by N-acetylmethionine. Archs Surg. Chicago 90, 11. Ethionine (I), a methionine analogue, is known to produce pancreatitis, and it is now shown that N-acetylmethionine (II) acts similarly under certain conditions. Intraperitoneal doses of 0.25-1 g II/kg given to young rats produced lesions of the pancreatic acini, consisting of loss of zymogen granules and of basophilic cytoplasmic material and acute pancreatitis. These lesions were similar to those produced by I and were likewise prevented by simultaneous administration of methionine. The pH of the administered solution was critical in bringing about pancreatic damage. In strongly acid solution stability of the N-acetyl group is ensured, but at a pH more alkaline than pH 5 the N-acetyl group undergoes hydrolysis and toxicity is lost. Pancreatic damage was restricted to the acini, the islets of Langerhans being unaffected. In addition, proximal nephrosis was observed in about one-third of the affected rats. Very slight hepatitis was found in a few animals, but in general there was no liver damage. This is in marked contrast to the hepatotoxicity of I.
NATURAL PRODUCTS
Cited in F.C.T. 1964, 2, 282) and 3,4-benzopyrene, traces of which are produced during roasting (ibid 1964, 2, 384). In addition, raw coffee oil (I) causes decreased growth and protein efficiency and liver enlargement in rats (ibm 1965, 3, 358) and this work has now been extended to an investigation of the toxicity of cafestol (II), a diterpene constituent of I. Up to 1.25 % of II, either in the free form or conjugated as a fatty acid monoester, is present in I. The toxicity of II was determined by the chick embryo test (ibid 1964, 2, 287; Fd Cosmet. Toxicol. 1964, 2, 717). Being insoluble in aqueous solutions, II was injected into the yolk sac of 6-day incubated eggs in 0.05 or 0.1 ml olive oil. Since olive oil itself was found to possess some toxicity (an LD50 of 9-94 ml or 9.11 g/kg egg weight), the LD5o of II had to be calculated and was found to be 4-15 mg/kg egg weight. Although II is quite toxic to the chick embryo, it does not necessarily follow that it is also harmful to mammals. This study emphasizes the necessity of taking into account the toxicity of the solvent in this type of test. 1026. No monkey nuts for crotalaria
Allen, J. R., Carstens, L. A. & Knezevic, A. L. (1965). Crotalaria spectabilis intoxication in Rhesus monkeys. Am. J. vet. Res. 26, 753. The vegetation and seeds of Crotalaria spectabilis (I) are toxic to most animals and to man, the toxic principle being the alkaloid monocrotaline. Details have already been given of the toxic effects of seeds of I to poultry (Cited in F.C.T. 1964, 2, 122). The liver appears to be the main site of attack in animals as well as in man and the present study shows that the monkey is no exception. Feeding diets containing 0.25-1.0% seeds of I to monkeys resulted in a loss in body weight and death within 162-263 days. Severe ascites, hydrothorax and subcutaneous oedema were manifest at autopsy. Fluid accumulation was attributed to severe liver injury with a consequent level of albumin synthesis inadequate to maintain the osmotic pressure of the blood, as reflected by a marked shift in the serum albumin/globulin ratio. Liver damage was extensive and consisted of vacuolar degeneration and haemorrhagic necrosis. The resulting distortion of liver architecture caused blockage of several bile canaliculi which contributed to a slight rise in serum bilirubin. Pulmonary oedema and haemorrhage were also found. 1027. Pancreatic lesions by a methionine derivative
Alvizouri, M., Vazquez, H., Macouzet, J. & Cortes, J. (1965). Pancreatic lesions by N-acetylmethionine. Archs Surg. Chicago 90, 11. Ethionine (I), a methionine analogue, is known to produce pancreatitis, and it is now shown that N-acetylmethionine (II) acts similarly under certain conditions. Intraperitoneal doses of 0.25-1 g II/kg given to young rats produced lesions of the pancreatic acini, consisting of loss of zymogen granules and of basophilic cytoplasmic material and acute pancreatitis. These lesions were similar to those produced by I and were likewise prevented by simultaneous administration of methionine. The pH of the administered solution was critical in bringing about pancreatic damage. In strongly acid solution stability of the N-acetyl group is ensured, but at a pH more alkaline than pH 5 the N-acetyl group undergoes hydrolysis and toxicity is lost. Pancreatic damage was restricted to the acini, the islets of Langerhans being unaffected. In addition, proximal nephrosis was observed in about one-third of the affected rats. Very slight hepatitis was found in a few animals, but in general there was no liver damage. This is in marked contrast to the hepatotoxicity of I.