Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca²âº balance protein levels.

Doxorubicin (DOX) causes long-term cardiomyopathy that is dependent on oxidative stress and contractility disorders. Tirapazamine (TP), an experimental adjuvant drug, passes the same red-ox transformation as DOX. The aim of the study was to evaluate an effect of tirapazamine on oxidative stress, contractile protein level, and cardiomyocyte necrosis in rats administered doxorubicin. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin. There were no significant changes in GSH/GSSG ratio, total glutathione, cTnI, AST, and SERCA2 level between DOX and TP+DOX groups. Cardiomyocyte necrosis was observed in groups 10TP and 10TP+DOX.

The redox imbalance and the reduction of contractile protein content in rat hearts administered with L-thyroxine and Doxorubicin.

Oxidative stress and disorders in calcium balance play a crucial role in the doxorubicin-induced cardiotoxicity. Moreover, many cardiotoxic targets of doxorubicin are regulated by iodothyronine hormones. The aim of the study was to evaluate effects of tetraiodothyronine (0.2, 2 mg/L) on oxidative stress in the cardiac muscle as well as contractility and cardiomyocyte damage markers in rats receiving doxorubicin (1.5 mg/kg) once a week for ten weeks. Doxorubicin was administered alone (DOX) or together with a lower (0.2T(4) + DOX) and higher dose of tetraiodothyronine (2T(4) + DOX). Two groups received only tetraiodothyronine (0.2T(4), 2T(4)). Coadministration of tetraiodothyronine and doxorubicin increased the level of lipid peroxidation products and reduced RyR2 level when compared to untreated control and group exposed exclusively to doxorubicin. Insignificant differences in SERCA2 and occasional histological changes were observed. In conclusion, an increase of tetraiodothyronine level may be an additional risk factor of redox imbalance and RyR2 reduction in anthracycline cardiotoxicity.

[Activity of catalase after administration of some ADH and MEOS inhibitors: in vitro investigation in rat liver homogenates]. / Aktywnosc katalazy po zastosowaniu wybranych inhibitorów ADH i MEOS, badania in vitro w homogenatach watroby szczurów.

In the first pass methanol biotransformation three enzymatic systems: alcohol dehydrogenase (ADH), microsomal alcohol oxidising system (MEOS) linked with cytochrome P-450 and catalase are involved. Because of the toxicity of methanol, which is directly caused by its toxic metabolites, the major task in clinical toxicology is to inhibit each of these enzymes to protect human life. The aim of this investigation was to check the influence of some effective inhibitors of ADH and MEOS: 4-methylpyrazole, cimetidine, EDTA and 1,10-phenantroline on the activity of catalase with methanol as a substrate and the comparison with 3-amino-1,2,4-triasole. Catalase activity in rat hepatic homogenates was measured spectrophotometrically in vitro at physiological pH 7.4 and temp. 37 degrees C, assaying the degree of methanol oxidation according to Handler and Thurman. The quantity of arising formaldehyde was measured according with the method of Nash. Our results have shown that catalase activity was inhibited to different extents by all investigated compounds at concentrations of 10(-3) mol/l, 2 x 10(-4) mol/l, 10(-4) mol/l, 2 x 10(-5) mol/l, 10(-5) mol/l. 1,10-Phenantroline was found to be a highly effective inhibitor in comparison with aminotriasole. 4-Methylpyrazole, EDTA, 1,10-phenantroline and aminotriasole are catalase competitive inhibitors and cimetidine is non-competitive inhibitor. 4-Methylpyrazole has shown higher affinity to the enzyme than aminotriasole.

[Risk assessment of known and new chemicals]. / Ocena ryzyka w odniesieniu do istniejacych i nowych zwiazków chemicznych.

It has become obvious that exposure to chemicals entails risk. Their hazardous and threatening effects may be not only direct but also indirect affecting microorganisms, animals and plants. This aspect of hazard and risk assessment is almost identical to that of toxicity. There are various categories of chemicals and for each of them risk assessment regulations have been developed. There are two major groups of chemicals: those which are already known and new ones. There are also some specific categories of chemical compounds, such as pesticides, biocides, medicinal products, cosmetics, food additives, feed additives, as well as radioactive substances and others. At present, the binding national and international regulations regarding different categories of chemical compounds are the subject of discussion in the member states of the European Union. In Poland, and attempt has been made to find appropriate examples of legal regulations that could be followed in our country, and this problem remains still open.