Zuzana Kyselova

Toxicological aspects of the use of phenolic compounds in disease prevention

Toxicological aspects of the use of phenolic compounds in disease prevention The consumption of a diet low in fat and enhanced by fruits and vegetables, especially rich in phenolic compounds, may reduce risks of many civilization diseases. The use of traditional medicines, mainly derived from plant sources, has become an attractive segment in the management of many lifestyle diseases. Concerning the application of dietary supplements (based on phenolic compounds) in common practice, the ongoing debate over possible adverse effects of certain nutrients and dosage levels is of great importance. Since dietary supplements are not classified as drugs, their potential toxicities and interactions have not been thoroughly evaluated. First, this review will introduce phenolic compounds as natural substances beneficial for human health. Second, the potential dual mode of action of flavonoids will be outlined. Third, potential deleterious impacts of phenolic compounds utilization will be discussed: pro-oxidant and estrogenic activities, cancerogenic potential, cytotoxic effects, apoptosis induction and flavonoid-drug interaction. Finally, future trends within the research field will be indicated.

Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats

Different experimental approaches in modelling cataractogenesis Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed.

Pycnogenol® efficiency on glycaemia, motor nerve conduction velocity and markers of oxidative stress in mild type diabetes in rats.

The aim of this study was to describe the effects of Pycnogenol® at various doses on preprandial and postprandial glucose levels, the levels of thiobarbituric acid reactive substances (TBARs) and N‐acetyl‐β‐d‐glucosaminidase (NAGA) and on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)‐induced diabetic rats. Pycnogenol® treatment (10, 20, 50 mg/kg body weight (b.w.)/day) lasted for 8 weeks after induction of diabetes.

Pycnogenol® improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats

We studied whether Pycnogenol® (PYC) may attenuate the development of experimental streptozotocin‐induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)‐producing molecules (gp91phox‐containing NADPH oxidase and NO‐signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha‐tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS‐producing enzymes and cytoskeletal components. Copyright

Effect of the pyridoindole antioxidant stobadine on sodium handling of renal Na,K-ATPase in rats with streptozotocin-induced diabetes.

Overload of reactive oxygen species during diabetes is known to impair cellular homeostasis and to promote deterioration of membrane function in the organism. The aim of the present study was to examine the effect of dietary supplementation with the pyridoindole atioxidant stobadine on functional properties of the renal Na, K-ATPase in diabetic rats. After 16 weeks of streptozotocin-induced diabetes (single intravenous dose of streptozotocin; 55 mg/kg), a significant inhibition (by 35%–42%) of the enzyme was observed throughout the range of NaCl 2–100 mmol/l, probably as an event of altered functional properties of Na,K-ATPase, suggested by the 42% decrease of the Vmax value. Administration of 0.05% (w/w) stobadine in the diet dramatically improved the function of renal Na,K-ATPase in diabetic rats with regard to sodium handling, as suggested by significant stimulation (by 104%–77% in accordance with increasing concentration of NaCl) of the enzyme over the whole NaCl concentration range investigated. This stimulatory effect was accompanied by an increase of Vmax value to the level of nondiabetic rats on standard diet. In conclusion, stobadine was found to antagonise the negative effects of diabetes on the renal Na,K-ATPase, preserving its normal function in regulation of intracellular homeostasis of Na+ and K+ ions.

Antioxidant SMe1EC2 may attenuate the disbalance of sodium homeostasis in the organism induced by higher intake of cholesterol.

The study was focused to the influence of higher intake of cholesterol on properties of the renal Na,K-ATPase, a key system in maintaining the homeostasis of sodium in the organism. Feeding for 4 weeks with cholesterol-enriched food for rats afflicted with hereditary hypertriglyceridemia by itself enhanced the activity of Na,K-ATPase, probably as a consequence of higher number of active enzyme molecules as suggested by 32xa0% increase of Vmax value. This may be hypothesized as a reason for the increased retention of sodium. Three-week-lasting treatment of animals kept on high cholesterol diet with antioxidant SMe1EC2 in a dose of 10xa0mgxa0kg−1xa0day−1 normalized the function of renal Na,K-ATPase to the level comparable in hypertriglyceridemic rats fed with the standard diet. Therefore, our results suggest that the antioxidant SMe1EC2 in the applied dose seems to be effective in the attenuation of cholesterol-induced retention of sodium. Treatment for 3xa0weeks with Fenofibrate in a dose of 100xa0mgxa0kg−1xa0day−1 reversed the function of renal Na,K-ATPase only slightly.