High-fat high-fructose diet and alpha-ketoglutarate affect mouse behavior that is accompanied by changes in oxidative stress response and energy metabolism in the cerebral cortex.

BACKGROUND: High caloric diets with high amounts of fats and sweeteners such as fructose may predispose organisms to neurodegenerative diseases. METHODS: This study aimed to examine the effects of a high-fat high-fructose diet (HFFD) on the behavior of mice, energy metabolism, and markers of oxidative stress in murine cerebral cortex. Dietary α-ketoglutarate (AKG) was chosen as a treatment which could modulate the putative effects of HFFD. RESULTS: We found that HFFD stimulated locomotion and defecation in mice, whereas an AKG-supplemented diet had a proclivity to promote anxiety-like behavior. HFFD stimulated lipid peroxidation, and in turn, the AKG-supplemented diet led to a higher ratio of reduced to oxidized glutathione, higher activity of NAD(P)H:quinone oxidoreductase 1, and higher mRNA levels of UDP-glucose 6-dehydrogenase and transcription factor EB. Both diets separately, but not in combination, led to a decrease in the activities of glutathione peroxidase, glutathione S-transferase, and phosphofructokinase. All experimental diets resulted in lower levels of transcripts of genes encoding pyruvate dehydrogenase kinase 4 (PDK4), glycine N-methyl transferase, and peroxisome proliferator receptor γ co-activator 1. CONCLUSIONS: Our results show that diet supplemented with AKG resulted in effects similar to those of HFFD on the cerebral cortex, but elicited substantial differences between these two diets with respect to behavior, glutathione-dependent detoxification, and processes related to autophagy. GENERAL SIGNIFICANCE: Our study provides insight into the metabolic effects of HFFD alone and in combination with alpha-ketoglutarate in the mouse brain.

Specific and combined effects of dietary ethanol and arginine on Drosophila melanogaster.

In this study, we have investigated specific and combined effects of essential amino acid, l-arginine, and ethanol (EtOH), a natural component of Drosophila melanogaster food, on a range of physiological and biochemical parameters of the flies. Rearing of D. melanogaster during two weeks on the food supplemented with 50 mM l-arginine decreased activities of catalase, glucose-6-phosphate dehydrogenase, and glutathione-S-transferase in males by about 28%, 60%, and 60%, respectively. At the same time, arginine-fed males had 40% higher levels of lipid peroxides and arginine-fed females had 36% low-molecular mass thiol levels as compared to the control. Arginine decreased resistance of fruit flies to heat stress in both sexes, resistance to starvation in females, and resistance to sodium nitroprusside (SNP) in males. Nevertheless, arginine increased resistance to SNP in females. Consumption of food supplemented with 10% EtOH increased resistance of fruit flies to starvation but made them more sensitive to SNP. On the contrary, arginine abrogated the ability of EtOH to increase starvation resistance in males and to decrease SNP resistance in both sexes.

High fat high fructose diet induces mild oxidative stress and reorganizes intermediary metabolism in male mouse liver: Alpha-ketoglutarate effects.

BACKGROUND: Diets rich in fats and/or carbohydrates are used to study obesity and related metabolic complications. We studied the effects of a high fat high fructose diet (HFFD) on intermediary metabolism and the development of oxidative stress in mouse liver and tested the ability of alpha-ketoglutarate to prevent HFFD-induced changes. METHODS: Male mice were fed a standard diet (10% kcal fat) or HFFD (45% kcal fat, 15% kcal fructose) with or without addition of 1% alpha-ketoglutarate (AKG) in drinking water for 8 weeks. RESULTS: The HFFD had no effect on body mass but activated fructolysis and glycolysis and induced inflammation and oxidative stress with a concomitant increase in activity of antioxidant enzymes in the mouse liver. HFFD-fed mice also showed lower mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and slightly increased intensity of mitochondrial respiration in liver compared to mice on the standard diet. No significant effects of HFFD on transcription of PDK2 and PGC1α, a peroxisome proliferator-activated receptor co-activator-1α, or protein levels of p-AMPK, an active form of AMP-activated protein kinase, were found. The addition of AKG to HFFD decreased oxidized glutathione levels, did not affect levels of lipid peroxides and PDK4 transcripts but increased activities of hexokinase and phosphofructokinase in mouse liver. CONCLUSIONS: Supplementation with AKG had weak modulating effects on HFFD-induced oxidative stress and changes in energetics in mouse liver. GENERAL SIGNIFICANCE: Our research expands the understanding of diet-induced metabolic switching and elucidates further roles of alpha-ketoglutarate as a metabolic regulator.

The pro-radical hydrogen peroxide as a stable hydroxyl radical distributor: lessons from pancreatic beta cells.

The toxic potential of H2O2 is limited, even if intracellular concentrations of H2O2 under conditions of oxidative stress increase to the micromolar concentration range. Its toxicity is mostly restricted to the oxidation of highly reactive thiol groups, some of which are functionally very important. Subsequently, the HO· radical is generated spontaneously from H2O2 in the Fenton reaction. The HO· radical is extremely toxic and destroys any biological structure. Due to the high reactivity, its action is limited to a locally restricted site of its generation. On the other hand, H2O2 with its stability and long half-life can reach virtually any site and distribute its toxic effect all over the cell. Thereby HO·, in spite of its ultra-short half-life (10-9 s), can execute its extraordinary toxic action at any target of the cell. In this oxidative stress scenario, H2O2 is the pro-radical, that spreads the toxic action of the HO· radical. It is the longevity of the H2O2 molecule allowing it to distribute its toxic action from the site of origin all over the cell and may even mediate intercellular communication. Thus, H2O2 acts as a spreader by transporting it to sites where the extremely short-lived toxic HO· radical can arise in the presence of "free iron". H2O2 and HO· act in concert due to their different complementary chemical properties. They are dependent upon each other while executing the toxic effects in oxidative stress under diabetic metabolic conditions in particular in the highly vulnerable pancreatic beta cell, which in contrast to many other cell types is so badly protected against oxidative stress due to its extremely low H2O2 inactivating enzyme capacity.

Chamomile as a potential remedy for obesity and metabolic syndrome.

Obesity is an increasing health concern related to many metabolic disorders, including metabolic syndrome, diabetes type 2 and cardiovascular diseases. Many studies suggest that herbal products can be useful dietary supplements for weight management due to the presence of numerous biologically active compounds, including antioxidant polyphenols that can counteract obesity-related oxidative stress. In this review we focus on Matricaria chamomilla, commonly known as chamomile, and one of the most popular medicinal plants in the world. Thanks to a high content of phenolic compounds and essential oils, preparations from chamomile flowers demonstrate a number of pharmacological effects, including antioxidant, anti-inflammatory, antimicrobial and sedative actions as well as improving gastrointestinal function. Several recent studies have shown certain positive effects of chamomile preparations in the prevention of obesity and complications of diabetes. These effects were associated with modulation of signaling pathways involving the AMP-activated protein kinase, NF-κB, Nrf2 and PPARγ transcription factors. However, the potential of chamomile in the management of obesity seems to be underestimated. This review summarizes current data on the use of chamomile and its individual components (apigenin, luteolin, essential oils) to treat obesity and related metabolic disorders in cell and animal models and in human studies. Special attention is paid to molecular mechanisms that can be involved in the anti-obesity effects of chamomile preparations. Limitation of chamomile usage is also analyzed.

Pleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent.

An intermediate of tricarboxylic acid cycle alpha-ketoglutarate (AKG) is involved in pleiotropic metabolic and regulatory pathways in the cell, including energy production, biosynthesis of certain amino acids, collagen biosynthesis, epigenetic regulation of gene expression, regulation of redox homeostasis, and detoxification of hazardous substances. Recently, AKG supplement was found to extend lifespan and delay the onset of age-associated decline in experimental models such as nematodes, fruit flies, yeasts, and mice. This review summarizes current knowledge on metabolic and regulatory functions of AKG and its potential anti-ageing effects. Impact on epigenetic regulation of ageing via being an obligate substrate of DNA and histone demethylases, direct antioxidant properties, and function as mimetic of caloric restriction and hormesis-induced agent are among proposed mechanisms of AKG geroprotective action. Due to influence on mitochondrial respiration, AKG can stimulate production of reactive oxygen species (ROS) by mitochondria. According to hormesis hypothesis, moderate stimulation of ROS production could have rather beneficial biological effects, than detrimental ones, because of the induction of defensive mechanisms that improve resistance to stressors and age-related diseases and slow down functional senescence. Discrepancies found in different models and limitations of AKG as a geroprotective drug are discussed.

Alpha-ketoglutarate enhances freeze-thaw tolerance and prevents carbohydrate-induced cell death of the yeast Saccharomyces cerevisiae.

Stress resistance and fermentative capability are important quality characteristics of baker's yeast. In the present study, we examined protective effects of exogenous alpha-ketoglutarate (AKG), an intermediate of the tricarboxylic acid cycle and amino acid metabolism, against freeze-thaw and carbohydrate-induced stresses in the yeast Saccharomyces cerevisiae. Growth on AKG-supplemented medium prevented a loss of viability and improved fermentative capacity of yeast cells after freeze-thaw treatment. The cells grown in the presence of AKG had higher levels of amino acids (e.g., proline), higher metabolic activity and total antioxidant capacity, and higher activities of catalase, NADP-dependent glutamate dehydrogenase and glutamine synthase compared to control ones. Both synthesis of amino acids and enhancement of antioxidant system capacity could be involved in AKG-improved freeze-thaw tolerance in S. cerevisiae. Cell viability dramatically decreased under incubation of stationary-phase yeast cells in 2% glucose or fructose solutions (in the absence of the other nutrients) as compared with incubation in distilled water or in 10 mM AKG solution. The decrease in cell viability was accompanied by acidification of the medium, and decrease in cellular respiration, aconitase activity, and levels of total protein and free amino acids. The supplementation with 10 mM AKG effectively prevented carbohydrate-induced yeast death. Protective mechanisms of AKG could be associated with the intensification of respiration and prevention of decreasing protein level as well as with direct antioxidant AKG action.

Dietary L-arginine accelerates pupation and promotes high protein levels but induces oxidative stress and reduces fecundity and life span in Drosophila melanogaster.

L-Arginine, a precursor of many amino acids and of nitric oxide, plays multiple important roles in nutrient metabolism and regulation of physiological functions. In this study, the effects of L-arginine-enriched diets on selected physiological responses and metabolic processes were assessed in Drosophila melanogaster. Dietary L-arginine at concentrations 5-20 mM accelerated larval development and increased body mass, and total protein concentrations in third instar larvae, but did not affect these parameters when diets contained 100 mM arginine. Young (2 days old) adult flies of both sexes reared on food supplemented with 20 and 100 mM L-arginine possessed higher total protein concentrations and lower glucose and triacylglycerol concentrations than controls. Additionally, flies fed 20 mM L-arginine had higher proline and uric acid concentrations. L-Arginine concentration in the diet also affected oxidative stress intensity in adult flies. Food with 20 mM L-arginine promoted lower protein thiol concentrations and higher catalase activity in flies of both sexes and higher concentrations of low molecular mass thiols in males. When flies were fed on a diet with 100 mM L-arginine, lower catalase activities and concentrations of protein thiols were found in both sexes as well as lower low molecular mass thiols in females. L-Arginine-fed males demonstrated higher climbing activity, whereas females showed higher cold tolerance and lower fecundity, compared with controls. Food containing 20 mM L-arginine shortened life span in both males and females. The results suggest that dietary L-arginine shows certain beneficial effects at the larval stage and in young adults. However, the long-term consumption of L-arginine-enriched food had unfavorable effects on D. melanogaster due to decreasing fecundity and life span.

Dietary alpha-ketoglutarate promotes higher protein and lower triacylglyceride levels and induces oxidative stress in larvae and young adults but not in middle-aged Drosophila melanogaster.

Alpha-ketoglutarate (AKG) is involved in multiple metabolic and regulatory pathways. In this work, the effects of AKG-supplemented diets on selected physiological responses and metabolic processes, including metabolism of reactive oxygen species, was assessed in larvae and adult (both 2 and 24days old) Drosophila melanogaster. Dietary supplementation with AKG resulted in dose-dependent effects on larval development, body composition and antioxidant status of third instar larvae. Larvae and young (2days post-eclosion) adult females fed on AKG shared similar metabolic changes such as higher total protein levels, lower triacylglyceride levels and higher values for oxidative stress indices, namely lipid peroxides and low molecular mass thiols. The latter indicated the development of oxidative stress which, in turn, may induce adaptive responses that can explain the higher resistance of AKG-fed young females to heat shock and hydrogen peroxide exposure. In contrast to young flies, middle-aged females (24days) on AKG-containing diet possessed higher total protein, glucose and triacylglyceride levels, whereas oxidative stress parameters were virtually the same as compared with control females of the same age. In parallel, females fed an AKG-supplemented diet showed lower fecundity, higher heat shock resistance but no change in oxidative stress resistance at middle age which in combination with levels of protein, glucose, and triacylglycerides can be considered as potentially beneficial AKG effects for aging organisms. To our best knowledge, this is the first study on age-matched AKG influence on animals' organism which shows that Drosophila may be used as a model for previous quick study in cost-efficient manner age-related AKG effects in mammals and humans.

Alpha-ketoglutarate reduces ethanol toxicity in Drosophila melanogaster by enhancing alcohol dehydrogenase activity and antioxidant capacity.

Ethanol at low concentrations (<4%) can serve as a food source for fruit fly Drosophila melanogaster, whereas at higher concentrations it may be toxic. In this work, protective effects of dietary alpha-ketoglutarate (AKG) against ethanol toxicity were studied. Food supplementation with 10-mM AKG alleviated toxic effects of 8% ethanol added to food, and improved fly development. Two-day-old adult flies, reared on diet containing both AKG and ethanol, possessed higher alcohol dehydrogenase (ADH) activity as compared with those reared on control diet or diet with ethanol only. Native gel electrophoresis data suggested that this combination diet might promote post-translational modifications of ADH protein with the formation of a highly active ADH form. The ethanol-containing diet led to significantly higher levels of triacylglycerides stored in adult flies, and this parameter was not altered by AKG supplement. The influence of diet on antioxidant defenses was also assessed. In ethanol-fed flies, catalase activity was higher in males and the levels of low molecular mass thiols were unchanged in both sexes compared to control values. Feeding on a mixture of AKG and ethanol did not affect catalase activity but caused a higher level of low molecular mass thiols compared to ethanol-fed flies. It can be concluded that both a stimulation of some components of antioxidant defense and the increase in ADH activity may be responsible for the protective effects of AKG diet supplementation in combination with ethanol. The results suggest that AKG might be useful as a treatment option to neutralize toxic effects of excessive ethanol intake and to improve the physiological state of D. melanogaster and other animals, potentially including humans.

Dietary alpha-ketoglutarate increases cold tolerance in Drosophila melanogaster and enhances protein pool and antioxidant defense in sex-specific manner.

Alpha-ketoglutarate (AKG) is an important intermediate in Krebs cycle which bridges the metabolism of amino acids and carbohydrates. Its effects as a dietary supplement on cold tolerance were studied in Drosophila melanogaster Canton S. Two-day-old adult flies fed at larval and adult stages with AKG at moderate concentrations (5-10mM) recovered faster from chill coma (0°C for 15min or 3h) than control ones. The beneficial effect of AKG on chill coma recovery was not found at its higher concentrations, which suggests hormetic like action of this keto acid. Time of 50% observed mortality after 2h recovery from continuous cold exposure (-1°C for 3-31h) (LTi50) was higher for flies reared on 10mM AKG compared with control ones, showing that the diet with AKG enhanced insect cold tolerance. In parallel with enhancement of cold tolerance, dietary AKG improved fly locomotor activity. Metabolic effects of AKG differed partly in males and females. In males fed on AKG, there were no differences in total protein and free amino acid levels, but the total antioxidant capacity, catalase activity and low molecular mass thiol content were higher than in control animals. In females, dietary AKG promoted higher total antioxidant capacity and higher levels of proteins, total amino acids, proline and low molecular mass thiols. The levels of lipid peroxides were lower in both fly sexes reared on AKG as compared with control ones. We conclude that both enhancement of antioxidant system capacity and synthesis of amino acids can be important for AKG-promoted cold tolerance in D. melanogaster. The involvement of AKG in metabolic pathways of Drosophila males and females is discussed.

Alpha-ketoglutarate attenuates toxic effects of sodium nitroprusside and hydrogen peroxide in Drosophila melanogaster.

The protective effects of dietary alpha-ketoglutarate (AKG) are described that aid fruit flies, Drosophila melanogaster, to resist sodium nitroprusside (SNP) and hydrogen peroxide toxicity. Food supplementation with 10mM AKG alleviated toxic effects of 1mM SNP added to food and improved fly development. Dietary AKG also prevented the increase in levels of oxidative stress markers seen in SNP-reared adult flies. In vitro AKG did not affect the rate of SNP decomposition and did not bind iron and nitrite ions released in this process. Alpha-ketoglutarate also displayed high H2O2-scavenging activity in vitro and efficiently protected adult flies against this compound in combined treatments. Based on the observed antioxidant activity of AKG, it may be suggested that the antioxidant mode of AKG action (apart from its cyanide-binding capability) may be used to prevent the toxic effects of SNP and improve general physiological state of D. melanogaster and other animals and humans.

Sodium chromate demonstrates some insulin-mimetic properties in the fruit fly Drosophila melanogaster.

The effects of food supplementation with sodium chromate at concentrations of 1-500 µM on development of Drosophila melanogaster larvae and food intake, carbohydrate and lipid pools in adult fruit flies were investigated. Food supplementation with hexavalent chromium (Na2CrO4) at high concentrations delayed larval development and decreased the percentage of larvae that pupated which indicated a relatively low toxicity. The supplement decreased glucose levels in fly hemolymph, but at concentrations of 5-25 µM increased fly carbohydrate reserves: hemolymph trehalose and whole body trehalose and glycogen. The data on parameters of carbohydrate metabolism show that chromate possesses some insulin-mimetic properties. The changes in metabolism of carbohydrates under chromate exposure were also accompanied by an increase in total lipid levels and in the portion of triacylglycerides among all lipids. Chromate addition to fly food did not affect male or female body mass, but reduced food consumption by females at all concentrations used, whereas in males only 500 µM chromate decreased food consumption. The data show that: (1) Cr(6+) has many of the same effects as Cr(3+) suggesting that it might be just as effective to treat diabetic states, likely as a result of intracellular reduction of Cr(6+) ions, and (2) the Drosophila model can be used to develop new approaches to investigate the molecular mechanisms of chromium as an insulin-mimetic. Although it is usually believed that hexavalent chromium possesses higher toxicity than the trivalent ion, due to its easier penetration into the cell, application of hexavalent chromium may substantially decrease the chromium doses needed to get the desired effects.

Molybdate partly mimics insulin-promoted metabolic effects in Drosophila melanogaster.

Molybdenum-containing salts have been found to attenuate diabetes complications in mammals by affecting processes normally regulated by insulin and thus were believed to mimic insulin activity. In this study, we used a fruit fly model to test sodium molybdate, Na2MoO4, action in relation to insulin-promoted processes and toxicity. We studied how larval food supplementation with sodium molybdate affected levels of body carbohydrates and lipids in two-day old adult Drosophila melanogaster. Molybdate salt, in the concentrations used (0.025, 0.05, 0.5, 5, and 10mM), showed low toxicity to fly larvae and slightly influenced development and the percentage of pupated animals. Additionally, sodium molybdate decreased the level of hemolymph glucose in males by 30%, and increased the level of hemolymph trehalose in flies of both sexes. These changes were accompanied by an increase in whole body trehalose and glycogen of about 30-90%. Although total lipid levels in flies of both sexes were depleted by 25%, an increased amount of triacylglycerides among total lipids was observed. These effects were not related to changes in food intake. Taken together, the present data let us suggest that sodium molybdate may at least partly mimic insulin-related effects in Drosophila.

2,4-dinitrophenol partially alleviates ferrocyanide-induced toxicity in Drosophila melanogaster.

The toxicity of potassium ferrocyanide (PFC) and protective effects of 2,4-dinitrophenol (DNP) under PFC treatment were tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with PFC at concentrations of 1.0 mM and mixtures with DNP in concentrations of 0.50 and 1.25 mM, either alone or in combination with 1.0 mM PFC. Food supplementation with PFC decreased larvae viability or pupation height, whereas when larvae were fed by PFC and DNP combination the decrease was less pronounced. Larval exposure to PFC and mixtures of DNP and PFC lowered activities of aconitase. Larval treatment with PFC resulted in higher carbonyl protein, uric acid, and low molecular mass thiols content and higher activity of thioredoxin reductase in adult flies, while DNP in mixtures with PFC relieved these effects. Furthermore, treatment with PFC/DNP mixtures resulted in higher activities of superoxide dismutase and glutathione-S-transferase. It is proposed that PFC toxicity is mainly related to the cyanide and iron ions, released during its decomposition. The potential mechanisms of protective DNP effects against PFC toxicity are discussed.

The mitochondrial uncoupler 2,4-dinitrophenol attenuates sodium nitroprusside-induced toxicity in Drosophila melanogaster: potential involvement of free radicals.

The toxicity of sodium nitroprusside (SNP) (an inducer of oxidative/nitrosative stress) and the attenuation of SNP effects by 2,4-dinitrophenol (DNP) (that induces mild uncoupling of respiration) were evaluated in the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with 1.0 mM SNP, 0.5 or 1.25 mM DNP, or with mixtures 1.0 mM SNP plus 0.5 or 1.25 mM DNP. Food supplementation with SNP decreased larval viability and pupation height whereas supplementation with DNP substantially reversed these changes. Biochemical analyses of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies emerged from control larvae and larvae fed on food supplemented with SNP, DNP, or SNP/DNP mixtures. Larval exposure to SNP lowered activities of aconitase, while the presence of DNP reduced the negative impact of SNP by raising aconitase activity back to near control levels. Larval treatment with SNP also elevated the contents of carbonyl protein, uric acid and low molecular mass thiols and produced higher activities of superoxide dismutase, glutathione S-transferase, glucose-6-phosphate dehydrogenase and thioredoxin reductase in adult flies. However, the presence of DNP in the food mixtures prevented SNP-induced changes in thioredoxin reductase and glucose-6-phosphate dehydrogenase activities, as well as uric acid and low-molecular-mass thiol content. The potential mechanisms by which DNP exerts protective effects against SNP toxicity are discussed.

S-nitrosoglutathione-induced toxicity in Drosophila melanogaster: Delayed pupation and induced mild oxidative/nitrosative stress in eclosed flies.

The toxicity of the nitric oxide donor S-nitrosoglutathione (GSNO) was tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with GSNO at concentrations of 1.0, 1.5 or 4.0mM. Food supplementation with GSNO caused a developmental delay in the flies. Biochemical analyses of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies that emerged from control larvae and larvae fed on food supplemented with GSNO. Larval exposure to GSNO resulted in lower activities of aconitase in both sexes and also lower activities of catalase and isocitrate dehydrogenase in adult males relative to the control cohort. Larval treatment with GSNO resulted in higher carbonyl protein content and higher activities of glucose-6-phosphate dehydrogenase in males and higher activities of superoxide dismutase and glutathione-S-transferase in both sexes. Among the parameters tested, aconitase activity and developmental end points may be useful early indicators of toxicity caused by GSNO.

Sodium nitroprusside toxicity in Drosophila melanogaster: delayed pupation, reduced adult emergence, and induced oxidative/nitrosative stress in eclosed flies.

The toxicity of sodium nitroprusside (SNP) was tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with SNP at concentrations of 0.01-1.5 mM. Food supplementation with SNP caused a developmental delay in flies and reduced adult eclosion. Biochemical analyses such as levels of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies emerged from control and SNP-fed larvae. Larval exposure to SNP resulted in lower activities of aconitase and catalase in adult flies relative to the control cohort. However, larval treatment with SNP led to higher carbonyl protein content and higher activities of superoxide dismutase, glucose-6-phosphate dehydrogenase, thioredoxin reductase, and glutathione-S-transferase in flies. Among the parameters tested, aconitase activity and developmental end points may be useful early indicators of toxicity caused by SNP. The study also suggests that the toxicity of SNP may arise not just from its direct effects, but also from its decomposition products such as nitric oxide and iron ions.

The golden root, Rhodiola rosea, prolongs lifespan but decreases oxidative stress resistance in yeast Saccharomyces cerevisiae.

The effect of aqueous extract from R. rosea root on lifespan and the activity of antioxidant enzymes in budding yeast Saccharomyces cerevisiae have been studied. The supplementation of the growth medium with R. rosea extract decreased survival of exponentially growing S. cerevisiae cells under H(2)O(2)-induced oxidative stress, but increased viability and reproduction success of yeast cells in stationary phase. The extract did not significantly affect catalase activity and decreased SOD activity in chronologically aged yeast population. These results suggest that R. rosea acts as a stressor for S. cerevisiae cells, what sensitizes yeast cells to oxidative stress at exponential phase, but induces adaptation in stationary phase cells demonstrating the positive effect on yeast survival without activation of major antioxidant enzymes.