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.

Flubendazole metabolism and biotransformation enzymes activities in healthy sheep and sheep with haemonchosis.

The aim of this project was to study the influence of haemonchosis, a common parasitic infection of small ruminants caused by Haemonchus contortus, on the activity of biotransformation enzymes and on in vitro flubendazole (FLU) biotransformation in liver and small intestine of lambs (Ovis aries). Twelve lambs were divided into three groups: non-infected animals, animals orally infected with larvae of H. contortus ISE strain for 7 weeks and for 11 weeks. At the end of the experiment, hepatic and intestinal subcellular fractions were prepared and used for assays of biotransformation enzymes activities and FLU metabolism testing. The activities of hepatic cytochromes P450, flavine monooxygenases and carbonyl-reducing enzymes were decreased in infected animals. UDP-glucuronosyl transferase activity was significantly lower (by 35%) in 11 weeks infected animals than that in control animals. When in vitro metabolism of FLU was compared in control and infected animals, significantly lower velocity of FLU reduction was found in infected animals. Slower FLU reduction may be beneficial for the haemonchosis treatment using FLU, because FLU will remain longer in the organism and could cause longer contact of parasites with FLU.

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.