Propylthiouracil-induced hypothyroid hyperlipidemic chick: a model for clofibrate-induced toxicity.

An animal model for clinically observed clofibrate (p-chlorophenoxy isobutyrate, CPIB)-induced toxicity has been tested. It is demonstrated that propylthiouracil-induced hypothyroid-hyperlipidemic chick develops severe toxic manifestations following clofibrate administration. Toxic symptoms are characterized by listlessness, drowziness, and extreme muscular weakness. This is associated with elevation of blood urea nitrogen, creatine phosphokinase, uric acid and glutamic oxaloacetic transaminase. Histological examination of muscle specimen from chicks exhibiting toxic syndrome showed degeneration and vacuolization of muscle fibers. The biochemical and histological changes observed are quite similar to those reported in clinical practice in some patients given clofibrate. It is suggested that this chick model could be used to investigate the biochemical basis of clofibrate toxicity.

[1]  R. J. Henry,et al.  Revised spectrophotometric methods for the determination of glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, and lactic acid dehydrogenase. , 1960, Technical bulletin of the Registry of Medical Technologists. American Society of Clinical Pathologists. Registry of Medical Technologists.

[2]  M. Schiphorst,et al.  A kinetic determination of ammonia in plasma. , 1974, Clinica chimica acta; international journal of clinical chemistry.

[3]  P. Segal,et al.  Effect of clofibrate on lipoprotein metabolism in hyperlipidemic rats. , 1972, The Journal of clinical investigation.

[4]  H. Gavras,et al.  Biliary excretion of 35 S-labelled propylthiouracil, methimazole and carbimazole in untreated and pentobarbitone pretreated rats. , 1972, Biochemical pharmacology.

[5]  E. Bernt,et al.  Creatine kinase in serum: 1. Determination of optimum reaction conditions. , 1976, Clinical chemistry.

[6]  F. Scheler,et al.  CLOFIBRATE-INDUCED MYOPATHY SYNDROME , 1976, The Lancet.

[7]  K. Evelyn,et al.  THE DETERMINATION OF BILIRUBIN WITH THE PHOTOELECTRIC COLORIMETER , 1937 .

[8]  R. Levy,et al.  Acute muscular syndrome associated with administration of clofibrate. , 1968, The New England journal of medicine.

[9]  L. Murchison,et al.  The effect of clofibrate on serum and faecal lipids. , 1972, Clinica chimica acta; international journal of clinical chemistry.

[10]  S. Grundy,et al.  Mechanisms of action of clofibrate on cholesterol metabolism in patients with hyperlipidemia. , 1972, Journal of lipid research.

[11]  M. Oliver.  FURTHER OBSERVATIONS ON THE EFFECTS OF ATROMID AND OF ETHYL CHLOROPHENOXYISOBUTYRATE ON SERUM LIPID LEVELS. , 1963, Journal of atherosclerosis research.

[12]  R. Levy,et al.  The Efficacy of Clofibrate (CPIB) in Familial Hyperlipoproteinemias , 1969 .

[13]  G. Malcom,et al.  Lipid lowering influence of ethyl p-chlorophenoxyisobutyrate in liver of rats fed high fat diets. , 1970, Metabolism: clinical and experimental.

[14]  K. Raheja,et al.  Glycogenolytic and hypolipidemic effect of clofibrate (CPIB) in the hypothyroid chick. , 1980, Comparative biochemistry and physiology. C: Comparative pharmacology.

[15]  T. Sasaoka,et al.  Untoward effects of clofibrate in hemodialyzed patients. , 1977, The New England journal of medicine.

[16]  K. Raheja,et al.  Effect of oral clofibrate administration on intestinal 3-O-methyl glucose absorption in rat and chick. , 1978, General pharmacology.

[17]  E. Wildi,et al.  Clofibrate, nephrotic syndrome, and histological changes in muscle. , 1973, Lancet.

[18]  A. Pierides,et al.  CLOFIBRATE-INDUCED MUSCLE DAMAGE IN PATIENTS WITH CHRONIC RENAL FAILURE , 1975, The Lancet.

[19]  C. H. Duncan,et al.  REDUCTION OF SERUM TRIGLYCERIDES AND CHOLESTEROL BY ETHYL P-CHLOROPHENOXY-ISOBUTYRATE (CPIB). , 1965, The American journal of cardiology.

[20]  M. Friedman,et al.  Effect of clofibrate on plasma lipids of rat and rabbit. , 1970, Atherosclerosis.