Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions.

Cancer is one of the most serious public health issues worldwide, demanding ongoing efforts to find novel therapeutic agents and approaches. Amid growing interest in the oncological applications of phytochemicals, particularly polyphenols, resveratrol-a naturally occurring polyphenolic stilbene derivative-has emerged as a candidate of interest. This review analyzes the pleiotropic anti-cancer effects of resveratrol, including its modulation of apoptotic pathways, cell cycle regulation, inflammation, angiogenesis, and metastasis, its interaction with cancer stem cells and the tumor microenvironment. The effects of resveratrol on mitochondrial functions, which are crucial to cancer development, are also discussed. Future research directions are identified, including the elucidation of specific molecular targets, to facilitate the clinical translation of resveratrol in cancer prevention and therapy.

Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

Beneficial and adverse effects of vitamin E on the kidney.

This article reviews the beneficial and adverse effects of high-dose vitamin E supplementation on the vitamin E status and renal function in human and rodent studies. The high doses of vitamin E, which can cause renal effects, were compared to upper limits of toxicity (UL) as established by various authorities worldwide. In recent mice studies with higher doses of vitamin E, several biomarkers of tissue toxicity and inflammation were found to be significantly elevated. In these biomarker studies, the severity of inflammation and the increased levels of the biomarkers are discussed together with the need to re-evaluate ULs, given the toxic effects of vitamin E on the kidney and emphasizing oxidative stress and inflammation. The controversy in the literature about vitamin E effects on the kidney is mainly caused by the dose-effects relations that do not give a clear view, neither in human nor animals studies. In addition, more recent studies on rodents with new biomarkers of oxidative stress and inflammation give new insights into possible mechanisms. In this review, the controversy is shown and an advice given on the vitamin E supplementation for renal health.

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where -0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

Selenium Anticancer Properties and Impact on Cellular Redox Status.

(1) Background: In this review, we provide information published in recent years on the chemical forms, main biological functions and especially on antioxidant and prooxidant activities of selenium. The main focus is put on the impact of selenoproteins on maintaining cellular redox balance and anticancerogenic function. Moreover, we summarize data on chemotherapeutic application of redox active selenium compounds. (2) Methods: In the first section, main aspects of metabolism and redox activity of selenium compounds is reviewed. The second outlines multiple biological functions, asserted when selenium is incorporated into the structure of selenoproteins. The final section focuses on anticancer activity of selenium and chemotherapeutic application of redox active selenium compounds as well. (3) Results: optimal dietary level of selenium ensures its proper antioxidant and anticancer activity. We pay special attention to antioxidant activities of selenium compounds, especially selenoproteins, and their importance in antioxidant defence. It is worth noting, that data on selenium anticancer properties is still contraversive. Moreover, selenium compounds as chemotherapeutic agents usually are used at supranutritional doses. (4) Conclusions: Selenium play a vital role for many organism systems due to its incorporation into selenoproteins structure. Selenium possesses antioxidant activity at optimal doses, while at supranutritional doses, it displays prooxidant activity. Redox active selenium compounds can be used for cancer treatment; recently special attention is put to selenium containing nanoparticles.

Effect of Zinc on the Oxidative Stress Biomarkers in the Brain of Nickel-Treated Mice.

The overexposure to nickel due to the extensive use of it in modern technology remains a major public health concern. The mechanisms of pathological effects of this metal remain elusive. The present study was devoted to evaluate the effect of nickel on the oxidative state of the brain cells of mice and to assess whether zinc as redox state modulator could efficiently protect cells against nickel's neurotoxicity. As oxidative stress biomarkers in the present study, we have measured the concentrations of reduced glutathione, metallothioneins, and malondialdehyde and the activity of the enzyme δ-aminolevulinate dehydratase. For the single metal exposure, mice were i.p. injected once with solutions of NiCl2 and/or ZnSO4; repeated exposure was performed i.p. injecting metal salt solutions for 14 days (once a day). The control mice received i.p. injections of saline. Results of our study demonstrate that single and 14 days of Ni2+ exposure decreased reduced glutathione and increased malondialdehyde contents in the brain of mice. Repeated Ni2+ administration significantly inhibited δ-aminolevulinate dehydratase while increasing brain metallothionein concentration at both exposure periods. Zinc exhibited a protective effect against nickel-induced glutathione and lipid peroxidation in brain cells of mice at both intervals of time, while repeated exposure to this metal significantly raised the brain metallothionein content. Repeated Zn2+ pretreatment protected δ-aminolevulinate dehydratase from Ni2+-induced inhibition and significantly increased metallothionein concentration at both investigated time intervals.

Post-exposure distribution of selenium and aluminum ions and their effects on superoxide dismutase activity in mouse brain.

The study was conducted to determine how aluminum (Al) and selenium (Se) ions alone and in combination affect superoxide dismutase (SOD) activity and to evaluate the distribution of these elements in the blood and the brain of laboratory mice. SOD activity in mouse brain was evaluated after single-time (within 24 h) and repeated (over 14 days) intraperitoneal (IP) injections of SeO32-, Al3+, and (SeO32-+Al3+) solutions. The control mice received IP injections of the same volume of saline. Aluminum concentration in mouse blood increased both after single-time and repeated injections of AlCl3 and the combined (AlCl3 + Na2SeO3) solutions. The concentration of Se increased in blood after single-time and repeated injections of Na2SeO3 and the combined (AlCl3 + Na2SeO3) solutions. After the single-time injection of the experimental solutions, the concentrations of both Al and Se in mouse brain remained at baseline, but after repeated injections of (AlCl3 + Na2SeO3) solutions increased aluminum concentration. A single IP injection of Al did not change SOD activity in mouse brain, while a single injection of Se or the Se + Al mixture decreased it. After 14 days, IP injections of Al or Se alone did not affect SOD activity, while their combination decreased it. Our results showed that Se ions decreased SOD activity in mouse brain after both single-time and repeated IP injections of selenium-containing solutions. The study failed to show a direct or linear effect of increased Al or Se concentrations on SOD activity in mouse brain.

Multiplicity of effects and health benefits of resveratrol.

Resveratrol is mainly found in grapes and red wine, also in some plants and fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries. Moreover, nowadays this compound is available as purified preparation and dietary supplement. Resveratrol provides a wide range of benefits, including cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood glucose-lowering and anticancer activities, hence it exhibits a complex mode of action. During the recent years, these properties have been widely studied in animal and human models, both in vitro and in vivo. This paper is intended to present information published during the recent years on the biological activities and multiple effects of resveratrol.

Subacute effects of cadmium and zinc ions on protein synthesis and cell death in mouse liver.

OBJECTIVE: The aim of this study was to evaluate in vivo the effects of cadmium and zinc ions on translational machinery and death of mouse liver cells. MATERIAL AND METHODS: Outbred mice received intraperitoneal injections of cadmium chloride solution (1.4 micromoles cadmium per 1 kg of body weight) and/or zinc sulfate solution (4.8 micromoles zinc per kg of body weight) three times per week for six weeks. Analogical volume of saline solution was injected to the control mice. Protein synthesis was evaluated by incorporation of [(14)C]-labeled leucine into peptides and proteins. Total tRNAs were isolated using deproteinized extract of liver tissue. Postmitochondrial supernatant was as a source of leucyl-tRNA synthetase. Activities of tRNA(Leu) and leucyl-tRNA synthetase were measured by an aminoacylation reaction using [(14)C]-labeled leucine. Liver cell apoptosis was detected by TUNEL assay using in situ cell death detection kit. RESULTS: A decrease in incorporation of [(14)C]-labeled leucine into proteins was detected in liver, kidney, and heart as well as diminution of tRNA(Leu) acceptor activity in cadmium-exposed liver. Cadmium caused activation of the leucyl-tRNA synthetase and induced liver cell apoptosis. Pretreatment of mice with zinc sulfate solution favored to protection of protein synthesis and acceptor activity of tRNA(Leu) against cadmium-induced inhibition. Under co-exposure of mouse liver to cadmium and zinc, activity of the leucyl-tRNA synthetase was at the level of control. Zinc did not influence TUNEL-positive cell number in cadmium-exposed mouse liver. CONCLUSIONS: Under subacute intoxication of mice by cadmium, zinc ions protect the translation machinery against inhibition, but do not decrease the number of apoptotic cells in the liver.

[Effects of lead ions on activities of tRNALeu and leucyl-tRNA synthetase of mouse liver]. / Svino jonu poveikis peliu kepenu tRNRLeu ir leucil-tRNR-sintetazes aktyvumui.

UNLABELLED: The objective of this study was to examine effect of lead ions on activities of mice liver tRNA(Leu) and leucyl-tRNA synthetase. MATERIAL AND METHODS: For researching white non-breed laboratory mice (20-25 g) were used. Intoxication with ions of lead was performed by injection of sublethal dose of lead acetate solution (50 mg ions of lead per 1 kg of body weight) into abdominal cavity of laboratory animals. Eight hours after intoxication from intoxicated and normal (control) mice liver preparations of tRNA and aminoacyl-tRNA synthetases were isolated. Acceptor activity of tRNA(Leu) and activity of leucyl-tRNA synthetase were determined in tRNA aminoacylation reaction using [(14)C]-labeled leucine. Actions of lead ions on acceptor activity of tRNA(Leu) and on activity of leucyl-tRNA synthetase from liver of control animals in vitro were determined after addition into reaction mixture different concentrations of lead acetate solution. RESULTS: It was determined that acceptor activity of mice liver tRNA(Leu) 8 h after intoxication with lead ions was reduced by 37 percent and activity of leucyl-tRNA synthetase was increased by 22 percent as compared to control. Experiments in vitro have shown that 10 micro M concentration of lead ions in reaction mixture stimulate acceptor activity of mice liver tRNA(Leu) by 17 percent, higher concentrations of lead ions (30-60 microM)--suppress it by 9-80 percent. The study of leucyl-tRNA synthetase activity in vitro has shown that 30 microM concentration of lead ions in reaction mixture increases activity of this enzyme by 16 percent, higher concentrations of lead ions (40-60 microM)--decrease by 17-23 percent. CONCLUSIONS: After 8 h intoxication with lead ions acceptor activity of tRNA(Leu) was decreased and activity of leucyl-tRNA synthetase was increased. It may be part of the compensatory mechanism of the cell to keep synthesis of proteins at the normal level under extreme conditions. Low concentrations of lead ions in reaction mixture increase tRNA(Leu) and leucyl-tRNA synthetase activities, higher concentrations of these ions decrease activity of those components of protein synthesis system. The results show that ions of lead directly suppress activity of both components of translation machinery.