Effects of a highly toxic coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl on intermediary metabolism: reduced triose phosphate content in rat liver cytosol.

The effects of a highly toxic coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB), on triose phosphate metabolizing enzymes were studied. Male Wistar rats received 25 mg/kg PenCB, i.p. At this dose the compound provokes a wasting syndrome. The activity of triose phosphate metabolizing enzymes, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase, glycerokinase, transaldolase and transketolase were significantly reduced by PenCB treatment to 50%, 60%, 50%, 70% and 40% of free-fed controls, respectively. An inhibition study with pyrazol, a specific inhibitor of alcohol dehydrogenase (ADH), showed that ADH makes about a 30% contribution to the formation of glycerol-3-phosphate from glyceraldehyde-3-phosphate. Our current study revealed that PenCB suppresses ADH at the protein expression level. The reduced formation of glycerol-3-phosphate from glyceraldehyde dehydrogenase by PenCB could be due to the suppression of ADH. The triose phosphate content in the liver cytosol of PenCB-treated rats was significantly lower than in free-fed controls. The suppression of triose phosphate metabolism could be a cause of the wasting syndrome provoked by highly toxic coplanar PCB.

Suppression of carbonic anhydrase III in rat liver by a dioxin-related toxic compound, coplanar polychlorinated biphenyl, 3, 3',4,4',5-pentachlorobiphenyl.

A coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB), significantly suppresses the expression of rat liver carbonic anhydrase III (CAIII), an enzyme which has recently been suggested to prevent from H(2)O(2)-inducible apoptosis. Marked changes in the CAIII levels of liver cytosol were observed in rats following doses of PenCB ranging from 0.5 to 25 mg/kg body weight and maximum suppression was observed at a dose of 10 mg/kg. Northern analysis revealed that the level of CAIII mRNA in rat liver was dramatically reduced by PenCB treatment while only weak suppression was observed in pair-fed controls. Two AU-rich elements, considered as a destabilizing signal of mRNA, were found in the 3'-untranslated region of CAIII sequenced after reverse transcription-PCR and 3'-rapid amplification of the cDNA end. Dramatic decrease of CAIII in rat liver by PenCB could account for the suppression of the defense system for oxidative stress.

Significant suppression of rat liver aldolase B by a toxic coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl.

A toxic coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB), significantly suppresses the expression of liver aldolase B in rats. Hepatic aldolase activity in PenCB-treated rats was significantly reduced to about 50% of that in free- and pair-fed control groups. The reduced aldolase activity following PenCB-treatment was due to the marked suppression of the expression of aldolase B shown by immunoblot analysis after SDS-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis. The suppression of rat liver aldolase B could be a key biochemical lesion caused by PenCB.

Significant induction of a 54-kDa protein in rat liver with homologous alignment to mouse selenium binding protein by a coplanar polychlorinated biphenyl, 3,4,5,3',4'-pentachlorobiphenyl and 3-methylcholanthrene.

A 54-kDa protein in rat liver cytosol was significantly induced by treatment with 3,4,5,3',4'-pentachlorobiphenyl (25 mg/kg, single i.p.) and 3-methylcholanthrene (20 mg/kg, once a day for 3 days, i.p.). The protein exhibited pI of 6.8 on two-dimensional gel electrophoresis. The amino acid sequences of peptide fragments from the protein digested in situ were highly similar to a selenium binding protein in mice and to the isoform acetaminophen binding protein in mice. The present result clearly demonstrates that a coplanar polychlorinated biphenyl and 3-methylcholanthrene are responsible for induction of selenium binding protein homologues. The physiological role of the mouse proteins, however, is not yet elucidated.

A coplanar PCB induces a selenium binding protein as a major cytosolic protein in rat liver.

We obtained evidence that a toxic coplanar polychlorinated biphenyl (PCB) induces a counterpart of murine 56kDa selenium binding protein in rat liver cytosol. A 54kDa protein in the liver cytosol was significantly induced by 3,3',4,4',5-pentachlorobiphenyl and proved to be a major cytosolic protein in the rat liver. The protein exhibited pI of 6.8 on two-dimensional gel electrophoresis. The amino acid sequence of peptide fragments from the protein digested in situ, was highly similar to a 56kDa selenium binding protein and similar to an acetaminophen binding protein in mice.

[Effect of a coplanar PCB on lipid metabolism: the remarkable difference between rats and guinea pigs].

We studied the effect of 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) on lipid metabolism by determining the level of triacylglycerol and total cholesterol in rats and guinea pigs. Male Wistar rats and male Hartley guinea pigs received PenCB in corn oil one at a dose of 25 mg/kg i.p. and 0.5 mg/kg i.p., respectively. Pair-fed control group of both species were treated with the vehicle and given the amount of chow matched with that taken by the PenCB-treated animals. Free-fed control group was treated with vehicle and was given the chow ad libitum. The plasma was collected on the day 5 after the treatment and the liver was removed. The plasma triacylglycerol level in guinea pigs treated with PenCB was significantly higher than those in free- and pair-fed controls, whereas no significant difference was observed in PenCB-treated rats from both control groups. The plasma cholesterol level was also higher in PenCB-treated guinea pigs than in the two control groups, though the level in rats was significantly lower than the corresponding control values. The hepatic triacylglycerol and cholesterol levels were increased significantly in both species by the PenCB treatment. Although lipid metabolism was disordered in both animals by treatment with PenCB, the responsiveness was remarkably different between guinea pigs and rats. These differences could be associated with species difference in susceptibility toward toxic chlorinated aromatic hydrocarbons.

Metabolic formation of dimethylamine and methylamine from basic drugs containing N-methyl group: a newly established chromatographic assay and its application to the determination of deaminase activity.

A new method of assaying deaminase activity was established in which methylamine and/or dimethylamine formed from drugs containing N,N-dimethyl or N-methyl group were derivatized with phenylisothiocyanate to phenylthiourea derivatives. After purification with Sep-PAK C18 cartridge, the derivatives were separated by a reversed phase high-performance liquid chromatography monitored by ultraviolet absorption. The recoveries and determination limits of methylamine and dimethylamine were over 55% and about 0.4 nmol/ml of incubation mixture, respectively. The method was used to measure the deaminase activities of liver microsomes of rats, rabbits and guinea pigs for 11 drugs. Of the compounds tested, diphenhydramine and diltiazem are deaminated with microsomes from all the above animal species; rat and rabbit liver microsomes also well deaminated promethazine. Most other drugs such as chlorpromazine, promazine, imipramine, amitriptyline and tetracaine were found to be poor substrates. In general, dimethylamine but not methylamine was the predominant metabolite formed from drugs containing N,N-dimethylamino group. The results also suggested that the deamination of these compounds takes place mainly via a one step mechanism, thus implying that the sequential reaction consisting of N-demethylation and elimination of ammonia is of minor importance. The relation between in vitro deaminase activity and the extent of the in vivo deamination for drugs is discussed.

"Atrioseptoplastia" para a correção de comunicação interatrial do tipo seio venoso com drenagem anômala de veia pulmonar em cava superior / Atrioseptoplasty for correction of interatrial defect of the venous sinus type with anomalous drainage of pulmonary vein in the superior vena cava

Descreve-se a tecnica da "atrioseptoplastia" para a correcao da comunicacao interatrial do tipo seio venoso com drenagem anomala de veia pulmonar em cava superior.Um retalho de parede anterior do atrio direito e utilizado para fechar o defeito septal desviando, simultaneamente, o fluxo da veia pulmonar para o atrio esquerdo. Um retalho de pericardio com tamanho e forma adequados e empregado para reconstruir o atrio de pericardio com tamanho e forma adequados e empregado para reconstruir o atrio direito e a veia cava superior. Dois pacientes portadores deste tipo de anomalia congenita foram operados por esta tecnica. Os resultados imediatos foram satisfatorios. Ressalta-se a simplicidade do procedimento e a facilidade de sua execucao