Monosodium glutamate-induced obesity changed the expression and activity of glutathione S-transferases in mouse heart and kidney.

Obesity may affect activity and/or expression of enzymes participating in xenobiotics' detoxification and antioxidant defense. This study sought to investigate the activities and expression of cardiac and renal glutathione S-transferase (GST) isoforms in order to reveal possible differences between obese and control mice. For this purpose, mice with monosodium glutamate (MSG)-induced obesity were used as an experimental model. Obesity was induced in newborn male mice by repeated s.c. administration of MSG. At 8 months of age, mice were sacrificed and specific activity, protein and mRNA expressions levels of GSTs were analyzed in their heart and kidney. In hearts of obese mice, specific activity of GST was decreased by 51% compared to control. This reduction was accompanied by a decline in GSTP-class protein and Gstp1/2 mRNA expression levels. In contrast, specific activity of GST was elevated by 31% in kidney of obese mice and this increase was accompanied by upregulation of GSTA-class protein and Gsta1/2 mRNA expressions. Increased capacity of renal GSTs together with GSTA upregulation may serve as compensatory mechanism against elevated oxidative stress, which accompanies obesity. On the other hand, decreased cardiac GST activity in obese mice and GSTP downregulation may worsen the defense against oxidative stress and harmful xenobiotics.

Oxidation as an important factor of protein damage: Implications for Maillard reaction.

Protein oxidation, the process caused especially by reactive oxygen and nitrogen species, is thought to play a major role in various oxidative processes within cells and is implicated in the development of many human diseases. This review provides a brief overview of the protein oxidation with the emphasis on the types of oxidation (oxidation of protein backbone and amino acid residues side chains, site-specific metal-catalysed protein oxidation), oxidationdependent generation of protein hydroperoxides, carbonyl derivatives and protein-protein cross-linkages. Nonenzymatic glycoxidation (also known as Maillard reaction) as an important factor of protein damage, consequences of oxidative protein impairment and related diseases as well as means of monitoring and assessment of protein modifications are discussed.

Interaction of anthocyanins with drug-metabolizing and antioxidant enzymes.

Anthocyanins are generally considered to be the largest and the most important group of water-soluble pigments in plants. They are widely consumed by humans as natural compounds of vegetables, fruits, and red wine. Anthocyanins as well as other flavonoids show protective qualities against variety of pathologies, including cardiovascular diseases, cancer, diabetes mellitus, neurodegeneration, inflammation, viral infections, and obesity. Many healthy properties of anthocyanins are related to their antioxidant potency. Broad evidence of beneficial effects of anthocyanins on human health has led to their increasing popularity in the form of food supplements and nutraceuticals. As the nutraceuticals contain concentrated bioactive agents, consumed doses exceed those that could be obtained from food. Therefore, apart from anticipated improvement of human health it is essential to have in mind possible unexpected effects of anthocyanins. Interaction of these compounds with drug-metabolizing enzymes and transporters may affect the fate of co-administered drugs and thus exert pharmacological consequences. On the other hand, the modulation of certain drug-metabolizing and antioxidant enzymes by anthocyanins can contribute to chemoprotection and antioxidant defense of organisms. The present review summarizes anthocyanin properties with emphasis on the antioxidant capacity and deals with the potential of anthocyanins to modulate phase I and II drug-metabolizing enzymes, transporters and antioxidant enzymes. The undesirable and/or beneficial outcomes of possible interactions of anthocyanins with drugs or industrial pollutants are also discussed.

The influence of oracin on reduction and toxicity of doxorubicin in hepatocytes and mammary epithelial cells MCF-10A.

The ways, how to increase effectiveness of doxorubicin (DOX) in cancer cells and decrease its toxicity in normal cells, have been intensively studied. In breast cancer cells MCF-7, isoquinoline derivative oracin (ORC) inhibited DOX reduction and increased DOX antiproliferative effect. The aim of this study was to test the influence of ORC on the reduction of DOX and its toxicity in hepatocytes and non-tumourous breast cells. The kinetics of DOX reduction was measured in cytosols from rat liver, human liver and human mammary epithelial cells MCF-10A. Activity and expression of carbonyl reductase 1 (CBR1) were assayed using menadione as a substrate and western blot analysis. End-point tests of viability served for study of cytotoxicity of DOX, ORC and DOX+ORC combinations in rat hepatocytes and MCF-10A cells. The inhibitory effect of ORC on DOX reductases was almost none in MCF-10A cells and mild in liver. CBR1 expression and activity was lower in non-tumourous MCF-10A cells than in cancer MCF-7 cells. Cytotoxicity tests showed that DOX+ORC combinations had significantly lower toxicity than DOX alone in MCF-10A cells as well as in hepatocytes. ORC significantly decreases DOX toxicity in MCF-10A and in hepatocytes. Therefore, concomitant use of ORC and DOX may protect normal cells against DOX toxicity.

Antioxidant and prooxidant properties of flavonoids.

The interest in possible health benefits of flavonoids has increased owing to their potent antioxidant and free radical scavenging activities observed in vitro. Nevertheless, the antioxidant efficacy of flavonoids in vivo is less documented and their prooxidant properties have been actually described in vivo. Due to their prooxidant properties, they are able to cause oxidative damage by reacting with various biomolecules, such as lipids, proteins and DNA. Hence, the aim of this review is to discuss both the antioxidant and prooxidant effects of flavonoids.

Evaluation of in vitro effects of natural substances of plant origin using a model of protein glycoxidation.

In an in vitro model with purified porcine aspartate aminotransferase (AST, EC 2.6.1.1) as the protein, the effects of phenolic antioxidants of plant origin (arbutin, methylarbutin, ferulic and isoferulic acids, o-coumaric and p-coumaric acids, quinic acid), flavonoids (baicalin and baicalein), and of hydroxycitric acid (HCA) at 0.5-50 mM concentration on the enzyme activities and on its glycation by 50 mM D-fructose as the glycating agent were studied. During incubation with AST at 37 degrees C up to 24 days, fructose alone decreased AST activities as a result of protein glycation. In the absence of fructose, 50 mM phenolic compounds gradually decreased AST activity, while no or a weak effect of individual compounds was found at 3 mM concentration. A direct negative effect on AST was pronounced with ferulic acid. On the other hand, beneficial influences of phenolic compounds on glycation of AST by fructose were found mostly at 3 mM concentration. Effects on glycation were vague at 50 mM concentration, probably due to a combination of direct negative influences and antiglycation effects of individual compounds. No effect, neither positive nor negative, on AST activity and protein glycation, was found with quinic acid. The flavonoid baicalin and its aglycon baicalein rapidly decreased the in vitro activity of the enzyme in all concentrations used (0.5-3 mM), and no beneficial effects of the compounds on glycation of the enzyme by fructose were found. The influence of HCA on glycation was concentration-depended, ranging from beneficial inhibition of glycation at 2.5 mM concentration to a strong decrease in AST activity at 10 mM HCA. Both the beneficial and undesirable effects of natural antioxidants should be considered in case they are used as antiglycation factors. The results obtained can contribute to the evaluation of quality of various generally recommended antioxidants.