Regulation of heme oxygenase gene expression by cobalt in rat liver and kidney.

The effect of heavy metals such as cobalt chloride and the corresponding metalloporphyrin on the transcription of the heme oxygenase gene in tissues was examined using cDNA for rat heme oxygenase as the probe. An increase in heme oxygenase mRNA level was observed in response to cobalt chloride and cobalt protoporphyrin treatment in both liver and kidney. Quantitative evaluation of the heme oxygenase transcript was obtained by determining the intensity of mRNA bands by scanning densitometry, and indicated that cobalt chloride increased heme oxygenase mRNA by 40-60-fold after 2 h of metal exposure.

Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats.

Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of heme arginate, a potent inducer of heme oxygenase (EC 1.14.

Cytochrome P450-dependent arachidonic acid metabolism in human kidney.

Cytochrome P450-dependent arachidonic acid metabolism in human kidney cortex from several postmortem subjects has been characterized. Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases. This pattern of metabolism was similar to that found in rabbit and rat kidneys.

Sensitivity of human tissue heme oxygenase to a new synthetic metalloporphyrin.

Heme oxygenase, the rate-limiting enzyme for heme degradation, can be inhibited by several new synthetic metalloporphyrins. Under certain conditions, a depression in heme oxygenase activity has important clinical significance in the treatment of hyperbilirubinemia, and, in this regard, tin-protoporphyrin has been shown to decrease the production of bilirubin in vitro as well as in vivo. Similarly, our study was concerned with finding a new metalloporphyrin which will inhibit heme oxygenase.

Changes of myocardial functions in acute hepatic porphyrias. Role of heme arginate administration.

In three patients with attacks of acute intermittent porphyria we found markedly impaired functions of the left ventricle accompanied by ECG changes that returned to normal after administration of heme arginate or cytochrome C administration. In nine patients with other types of porphyria, and in one patient with acute intermittent porphyria not suffering an attack, no significant changes of left ventricle function were observed. The changes seen in patients with an acute attack may be ascribed to acute myocardial hypoxia resulting from defective biosynthesis of heme.

[A new model for testing substances affecting the synthesis of heme].

A new model for experimental studies of substances influencing porphyrin metabolism has been created. The model is formed by yeast Saccharomyces cerevisiae (RIBM-75) grown semiaerobically. The main advantages of this model include simple evocation of porphyria (intracellular accumulation of porphyrins in semiaerobic conditions) and direct measurement of experimental values (intracellular and extracellular concentrations of porphyrins).

Properties of human kidney heme oxygenase: inhibition by synthetic heme analogues and metalloporphyrins.

Heme oxygenase activities in human kidney microsomes were found to be from 0.238 to 0.620 nmol of bilirubin/mg/hr (mean 0.

Porphyrinostatic effect of isonicotinic acid hydrazide on porphyric chick embryo and yeast.

1. The common feature of "inducible" forms of hepatic porphyria is an increased activity of delta-amino-levulinate/ALA/synthase. 2.

Solid phase extraction and isocratic separation of urinary porphyrins by HPLC.

A method for determining urine porphyrins by HPLC is described. In the preliminary step, porphyrins are purified in high yields and concentrated by low pressure reverse-phase chromatography on C18 (octadecylsilane bonded silica) cartridge. Porphyrins are stable for 10 days after adsorption on C18 cartridge.

Resin hemoperfusion in hepatic porphyrias.

In three types of hepatic porphyrias, 32 hemoperfusions over polyhema-coated Amberlite XAD-2 resin were performed. An attack of acute intermittent porphyria subsided after a 6-h hemoperfusion. During the procedure, 13 L of plasma was completely cleared of porphyrins.