RESUMO

1. The Phase II in vitro metabolism of 3-methylindole (3MI) metabolites was investigated in pigs to determine the possible relationship between 3MI Phase II metabolism and 3MI accumulation in fat. Sulphation and glucuronidation of five of the seven major metabolites found to be produced by porcine microsomes was investigated using porcine cytosol and microsomes, respectively. The possible formation of glutathione conjugates was also investigated using microsomally activated 3MI intermediate(s). 2. No sulphation or glucuronidation was observed for metabolites 3-hydroxy-3-methyloxindole, 3-methyloxindole, indole-3-carbinol or 2-aminoacetophenone; however, 5-hydroxy-3-methylindole (5-OH-3MI) was conjugated with both sulphate and glucuronic acid. 3. The enzyme responsible for sulphation of 5-OH-3MI was identified as the thermostable form of phenol-sulphotransferase (TS-PST) based on its susceptibility to TS-PST inhibitors and the correlation between sulphation of 5-OH-3MI and sulphation of the prototype substrate p-nitrophenol (r = 0.94, p < 0.001). 4. A 3MI-glutathione adduct was identified in microsomal incubations containing 3MI and glutathione. 5. Sulphation of 5-OH-3MI was high in pigs with low levels of 3MI in fat. No relationship was observed between 3MI levels in fat and either glutathione transferase or glucuronidation activities in liver.

Assuntos

Arilsulfotransferase , Fígado/metabolismo , Escatol/metabolismo , Tecido Adiposo/química , Tecido Adiposo/metabolismo , Animais , Citosol/metabolismo , Inibidores Enzimáticos/farmacologia , Ácido Glucurônico/química , Ácido Glucurônico/metabolismo , Glutationa/química , Masculino , Microssomos Hepáticos/metabolismo , Nitrofenóis/metabolismo , Escatol/química , Sulfatos/química , Sulfatos/metabolismo , Sulfotransferases/antagonistas & inibidores , Sulfotransferases/metabolismo , Suínos

RESUMO

Cobalt increases the red cell mass in both man and animals by increasing the production of erythropoietin. Since meat-type chickens can develop pulmonary hypertension from increased erythropoiesis and polycythaemia, two trials were conducted to investigate the role of cobalt on broiler chicken erythropoiesis and pulmonary hypertension. The results showed that feeding cobaltous chloride at 500 parts/10(6) to meat-type chickens from 1-day-old for 42 days significantly increased haemoglobin content and, to a lesser extent red blood cell count, and haematocrit. No effect was observed on mean corpuscular volume. Increased haemoglobin content was linearly correlated with pulmonary hypertension as measured by the right ventricle weight to total ventricle weight ratio (RV:TV). Levels of malondialdehyde in cardiac tissue were also correlated with the RV:TV ratio, suggesting that peroxidative damage may be related to ventricular hypertrophy. Chickens fed cobalt showed a significantly higher incidence of right ventricular hypertrophy and right ventricular failure and 18.3% developed ascites.