Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location.

These studies try to elucidate why isocoproporphyrin appears in hexachlorobenzene-poisoned rats' feces. Chronic exposure of hexachlorobenzene to rats produces an experimental model for human porphyria cutanea tarda. After 8 weeks of treatment, rats showed high porphyrin excreta and 50% inhibition of liver uroporphyrinogen decarboxylase activity.

Disturbances on delta aminolevulinate dehydratase (ALA-D) enzyme activity by Pb2+, Cd2+, Cu2+, Mg2+, Zn2+, Na+, K+ and Li+: analysis based on coordination geometry and acid-base Lewis capacity.

ALA-D (EC 4.2.1.

Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver.

In the present study, the effects of hexachlorobenzene (HCB) on epidermal growth factor receptor (EGFR) content of liver microsomes and plasma membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were investigated. In addition, we studied the parameters of the tyrosine kinase signalling pathway such as protein tyrosine kinase (PTK) activity and phosphotyrosine content in microsomal and cytosolic protein. To determine whether the observed alterations were correlated with a manifestation of overt toxicity, a single very low dose of HCB (1mg/kg body wt) and two much higher doses (100 and 1000 mg/kg body wt), the highest being toxicologically significant in that it reduced serum thyroxine (T(4)) and inhibited uroporphyrinogen decarboxylase (URO-D) (EC 4.

Ontogeny of 5-aminolevulinic dehydratase and porphobilinogen deaminase activities in the yolk sac membrane and liver of chick embryos.

1. Chick embryos of 7, 9, 11, 12, 13, 14, 15, 17 and 19 d of embryonic development were examined to determine the activities of 5-aminolevulinic dehydratase (ALA-D, EC 4.2.

Hexachlorobenzene, a dioxin-type compound, increases malic enzyme gene transcription through a mechanism involving the thyroid hormone response element.

Hexachlorobenzene (HCB) is a dioxin-type chemical that acts mainly through the aryl hydrocarbon receptor. Chronic exposure of rats to HCB increases the activity of malic enzyme (ME). In this report, we show that this increase is correlated with an induction of ME messenger RNA (mRNA) levels, with the maximal HCB effect achieved after 9 days of intoxication.

[Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene].

Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of laboratory animals to HCB triggers porphyria, induction of liver microsomal enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors. Previous findings from our laboratory have shown that HCB increased the activity of the liver thyroid-responsive enzymes: malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) without any change in the mytochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD).

Hexachlorobenzene-induced alterations of rat hepatic microsomal membrane function.

The time and dose-dependent effects of the in vivo administration of hexachlorobenzene (HCB), on hepatic microsomal membrane functions, were studied in female Wistar rats. Administration of HCB (100 mg/100 g b.w.

Hepatic indices of thyroid status in rats treated with hexachlorobenzene.

The functional thyroid status of hexachlorobenzene (HCB)-treated rats was studied. HCB caused a depletion of serum thyroxine (T4), but did not change L-3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the thyroid regulated mitochondrial enzyme L-glycerolphosphate dehydrogenase (LGPD) and cytosolic enzymes, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were assayed in livers of normal and HCB (100 mg/100 g bw) treated Wistar rats.

Studies on the decrease of liver cytochrome P-450 content by triiodothyronine.

In the rat liver, the microsomal content of cytochrome P-450 decreased by 50% after triiodothyronine (T3) administration. The molecular basis for the decreased cytochrome P-450 levels was investigated. The activities of the enzymes involved in heme synthesis or degradation were not altered by thyroid hormone administration.

Further evidence for an essential histidyl residue at the active site of pig liver 5-aminolevulinic acid dehydratase.

Photoxidation with methylene blue and rose bengal and chemical modification by diethylpryrocarbonate of pig liver 5-aminolevulinic acid dehydratase produced strong inactivation of the enzyme which was concentration dependent. Loss of enzyme activity by both photoxidation and ethoxyformylation was pH and time-dependent and protected by the presence of the substate and competitive inhibitors. The rate of inactivation was directly related to the state of protonation of histidyl groups, the unprotonated from being modified at a much faster rate than the protonated form.

Enhanced thyroxine metabolism in hexachlorobenzene-intoxicated rats.

The effect of hexachlorobenzene (HCB) (1 g/kg bw) administration for 4 weeks, on thyroxine (T4) and triiodothyronine (T3) metabolism was studied in Wistar rats. The effect on serum binding of T4 has also been studied. Animals were injected with a tracer dose of either labeled hormone and by examining serum L-125I-T4 and L-125-I-T3, kinetics of radiolabeled hormones metabolism were calculated.

The isolation and identification of indigoid pigments from urine.

A purple pigment, phyriaviolin, and a blue pigment, phyriaazulin, have been found in relatively large amounts in the urine of patients suffering from two diverse pathological conditions, porphyria cutanea tarda and Crohn's disease. The two pigments have been characterised by chemical, spectroscopic, and chromatographic studies and identified to be indirubin and indigo (indigotin). Possible reasons for their formation are discussed.

Effect of triiodothyronine in the regulation of haem biosynthetic pathway.

Triiodothyronine administration to thyroidectomized animals, decreased cytochrome P-450 content by 50%. Haem oxygenase was not modified by triiodothyronine treatment, either alone or with a suboptimal dose of CoCl2. Under the same conditions hepatic delta-amino-laevulinic acid synthase activity was not affected.

Progesterone, its A/B cis reduction and delta aminolevulinic acid synthetase in the developing hen.

In steroidogenic tissues of the developing hen, specially in the right ovary, 5 beta reductase (Rase) increases after hatching. delta aminolevulinic acid synthetase (ALAs) in these tissues is more active than hepatic ALAs during most embryonic stages. But after hatching, only hepatic and adrenal ALAs increase sharply; ALAs increases only moderately in the left ovary and descends to very low values in the right one.

The isolation of a new compound from urine of humans with porphyria cutanea tarda.

A method is reported for the isolation of phyriaviolin, a new compound from human porphyria cutanea tarda urine. The substance has been crystallized and some of its properties are described.

Macrocyclic intermediates in the biosynthesis of porphyrins.

The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates.

Studies on cow liver porphobilinogen deaminase.

Further properties of cow liver deaminase are reported. Highly purified deaminase migrated as a single badn on starch and polycrylamide gels electrophoresis. Molecular weight determinations by means of gel filtration on calibrated columns of Sephadex G-100, Sepharose 4 B and B 10-Gel P-100, gave values of 40 000 +/- 4 000.

Pentacarboxylic intermediates in haem biosynthesis.

The incorporation of the four possible type III porphyrinogens into protoporphyrin is described and their various rates or conversion are discussed. The techniques used involved the incubation of the porphyrinogens in chicken red cell haemolysates followed by extraction and characterisation of the end products on HPLC and TLC. Porphyrin 5 b c d was shown to be more slowly incorporated than porphyrins 5 a b d, 5 a c d and 5 a b c.

Hepta- and hexa-carboxylic porphyrinogen intermediates in haem biosynthesis.

In the course of our studies on intermediates in normal and abnormal metabolism of porphyrins we have synthesised a number of porphyrins related to uroporphyrin-III and compared them with materials isolated from natural sources. In the present paper we show that the corresponding porphyrinogens are all metabolised to protoporphyrin-IX by haemolysates of chicken erythrocytes, but at different rates. The results are discussed in relation to our conclusions concerning the preferred pathway of degradation of uro'gen-III to coproporphyrinogen-III, which indicate a clockwise sequence of decarboxylation reactions.