Chloroplast phosphate transporter CrPHT4-7 regulates phosphate homeostasis and photosynthesis in Chlamydomonas.

In eukaryotic cells, phosphorus is assimilated and utilized primarily as phosphate (Pi). Pi homeostasis is mediated by transporters that have not yet been adequately characterized in green algae. This study reports on PHOSPHATE TRANSPORTER 4-7 (CrPHT4-7) from Chlamydomonas reinhardtii, a member of the PHT4 transporter family, which exhibits remarkable similarity to AtPHT4;4 from Arabidopsis (Arabidopsis thaliana), a chloroplastic ascorbate transporter. Using fluorescent protein tagging, we show that CrPHT4-7 resides in the chloroplast envelope membrane. Crpht4-7 mutants, generated by the CRISPR/Cas12a-mediated single-strand templated repair, show retarded growth, especially in high light, reduced ATP level, strong ascorbate accumulation, and diminished non-photochemical quenching in high light. On the other hand, total cellular phosphorous content was unaffected, and the phenotype of the Crpht4-7 mutants could not be alleviated by ample Pi supply. CrPHT4-7-overexpressing lines exhibit enhanced biomass accumulation under high light conditions in comparison with the wild-type strain. Expressing CrPHT4-7 in a yeast (Saccharomyces cerevisiae) strain lacking Pi transporters substantially recovered its slow growth phenotype, demonstrating that CrPHT4-7 transports Pi. Even though CrPHT4-7 shows a high degree of similarity to AtPHT4;4, it does not display any substantial ascorbate transport activity in yeast or intact algal cells. Thus, the results demonstrate that CrPHT4-7 functions as a chloroplastic Pi transporter essential for maintaining Pi homeostasis and photosynthesis in C. reinhardtii.

Reaction of Partially Methylated Polygalacturonic Acid with Iron(III) Chloride and Characterization of a New Mixed Chloride-Polygalacturonate Complex.

We have described a new route for the preparation of partially methylated polygalacturonic acid containing hydrolyzed (acidic) and unhydrolyzed (methyl esterified) carboxylate groups in a ratio of 1:1 (PGA, compound 1), and one of its basic FeIII-salts (compound 2) with a ~1:2 FeIII:GA stoichiometry (GA means galacturonic acid and methylated galacturonic acid units). The partially hydrolyzed pectin was transformed into compound 1 with the use of double ion exchange with a strongly acidic macroreticular sulfonated styrene-divinylbenzene copolymer as a hydrogen ion source. The reaction of compound 1 with FeCl3 resulted in compound 2. Compound 2 has a polymeric nature and contains binuclear FeIII(µ-O)(µ-OH)FeIII core units with two kinds of distorted octahedral iron geometries. The salt-forming acidic and methylated GA units of compound 1 are coordinated to FeIII centers in asymmetric bidentate-chelating and -bridging (via C=O group and glycosidic oxygen) modes, respectively. Two kinds of outer-sphere chloride anions were also detected by XPS in various chemical environments fixed by different sets of hydrogen bonds. We also observed a partial reduction of FeIII into FeII due to the ring-opening of the chain-end GA units of compound 1. This reaction provides a new route to determine the number of chain-ends in compound 2, and with the use of the number of GA units calculated from charge neutrality, the average length of these chains and the average molecular weight were also determined. The average molecular weight of the partially methylated polygalacturonic acid used in the industrial-scale production of commercial anti-anemic iron-polygalacturonate agents was ~50,000 g/mol. Compound 2 was also characterized by IR, Mössbauer, and X-ray photoelectron spectroscopy, and magnetic susceptibility measurements. These results on the structure and average molecular weight of basic iron(III) polygalacturonate provide a tool to design Fe-PGA complexes with tuned iron-releasing properties.

The mechanism of photosystem-II inactivation during sulphur deprivation-induced H2 production in Chlamydomonas reinhardtii.

Sulphur limitation may restrain cell growth and viability. In the green alga Chlamydomonas reinhardtii, sulphur limitation may induce H2 production lasting for several days, which can be exploited as a renewable energy source. Sulphur limitation causes a large number of physiological changes, including the inactivation of photosystem II (PSII), leading to the establishment of hypoxia, essential for the increase in hydrogenase expression and activity. The inactivation of PSII has long been assumed to be caused by the sulphur-limited turnover of its reaction center protein PsbA. Here we reinvestigated this issue in detail and show that: (i) upon transferring Chlamydomonas cells to sulphur-free media, the cellular sulphur content decreases only by about 25%; (ii) as demonstrated by lincomycin treatments, PsbA has a significant turnover, and other photosynthetic subunits, namely RbcL and CP43, are degraded more rapidly than PsbA. On the other hand, sulphur limitation imposes oxidative stress early on, most probably involving the formation of singlet oxygen in PSII, which leads to an increase in the expression of GDP-L-galactose phosphorylase, playing an essential role in ascorbate biosynthesis. When accumulated to the millimolar concentration range, ascorbate may inactivate the oxygen-evolving complex and provide electrons to PSII, albeit at a low rate. In the absence of a functional donor side and sufficient electron transport, PSII reaction centers are inactivated and degraded. We therefore demonstrate that the inactivation of PSII is a complex and multistep process, which may serve to mitigate the damaging effects of sulphur limitation.

[Significance of the examination of the metal element content of herbal extracts in adjuvant therapy]. / Gyógynövénykivonatok fémelemtartalom-vizsgálatának jelentosége adjuváns terápiában.

The consumption of herbal teas is becoming more and more popular nowadays both as luxury foods and a complementary part of medical therapy. Beside the organic agents of medicinal plants, the presence of inorganic ions is also relevant in exerting the favorable pharmacological effect. The author briefly summarizes the importance of some essential metal ions and their quantitative values in teas applied in the adjuvant therapy of diabetes and used as diuretics. The common feature of teas used in diabetes is that they contain a measurable amount of chromium and the concentration of most essential elements (such as K, Mg, Mn and Zn) is significant, which can be considered as a mineral source for some metal ions. Diuretic herbs have an outstanding K content, but from the point of view of diuresis, the large K/Na molar ratio above 50 is relevant. Orv Hetil. 2018; 159(18): 713-719.

Antihyperlipidemic Effects of Sour Cherries Characterized by Different In Vitro Antioxidant Power and Polyphenolic Composition.

The aims of the present study were to clarify in vivo effects of three sour cherry cultivars characterized by different polyphenolic composition in hyperlipidemic animals in a short term experiment. The three different sour cherry cultivars were chosen based on their total in vitro antioxidant capacity, total polyphenolic, monomeric anthocyanin and flavonoid content. Male Wistar rats were divided randomly into eight groups: rats kept on normal diet (control) and normal diet supplied with sour cherry powder of one of the three cultivars; others were kept on fat-rich diet and fat-rich diet supplied with sour cherry powder prepared from one of the three cultivars. The treatment lasted 10 days. Lyophilized sour cherry administered in the diet decreased both total cholesterol and LDL cholesterol levels, and increased the HDL cholesterol concentration in sera of hyperlipidemic animals. Significant differences were found in the efficacy of different sour cherry cultivars in case of hyperlipidemia. Sour cherries characterized by higher polyphenol content seem to have a more pronounced effect on serum cholesterol levels. Our results suggest that besides anthocyanins, colourless polyphenols also have lipid lowering effect.

Antioxidant value and element content in some tinctures used in medication.

Tinctures are almost the oldest medicines and their use is substantial in the medication nowadays as well. The antioxidant values by ferric reducing/antioxidant power (FRAP) method and element content by inductively coupled plasma optical emission spectrometry (ICP-OES) were investigated in some tinctures official in the VII. and VIII. Pharmacopoeia Hungarica. The highest FRAP values were found for volatile oil containing Tinctura Aurantii amari epicarpii et mesocarpii, Tinctura Amara and Tinctura Valerianae (764.54 ± 19.90; 757.37 ± 14.46; 826.40 ± 5.89 µmol l⁻¹, respectively). The correlations between the FRAP values and dilution with different alcohol content in Tinctura Chinae, Tinctura Ipecacuanhae normata and Tinctura Strychni were also investigated. Remarkable differences were found between the element concentrations in the different tinctures. The element contents in tinctures are not so high in absolute values nevertheless the presence of essential selenium, zinc, manganese and copper is important since they have key role in the antioxidant system. The common feature of the tinctures seems to be the lithium content. The Ca to Mg concentration ratio was found to be shifted towards magnesium in some of the tinctures that can show a higher Mg absorption which could affect against the proinflammatoric processes in the cases of gastrointestinal diseases.

[Mineral content of some herbs and plant extracts with anti-inflammatory effect used in gastrointestinal diseases]. / Az emésztorendszer betegségeiben alkalmazható, gyulladáscsökkento hatással rendelkezo néhány gyógynövény és -kivonat ásványielem-tartalmának jelentosége.

INTRODUCTION: In gastrointestinal diseases folk medicine usually recommends herbs and teas with antiinflammatory activities, especially mucilage and bitter agent containing plants. The use of stomatics as adjuvant therapy in medical practice is frequent. AIM: The authors explored the mineral element content of some herbs, because mineral elements may have significant role in the development and treatment of gastrointestinal diseases, and a close connection between the presence or absence of mineral elements and inflammatory mediators was noted. METHODS: The mineral content in Trigonellae foenugraeci semen, Farfarae folium et flos, Taraxaci radix and Cichorii radix and teas prepared from these herbs was determined using inductively coupled plasma optical emission spectrometry. The results were evaluated from nutritional and biomedical points of view. RESULTS: Farfarae folium et flos tea was found to be a rich source of calcium, chromium, manganese and molybdenum. Trigonellae foenugraeci semen, Taraxaci radix and Cichorii radix displayed favourable calcium to magnesium ratio (1-1.5) and they contained other elements (manganese, iron, copper, zinc) which may have significant role in the immune defence system. CONCLUSION: The beneficial therapeutic effect of the studied herbs may be related to their mineral element content.

Diabetes and trace elements / Diabetes és a nyomelemek

Ionic or complex compounds of certain trace elements are essential for the proper functioning of the human body in numerous biochemical processes. Their absence or accumulation causes many health problems and diseases. In the past, trace elements have been thought to be a key factor in the treatment of insulin resistance and diabetes, however, the importance and lack of trace elements in the development of diabetes or the assessment of trace element status in the development and treatment of complications are still controversial. Therefore, the authors summarize the role of trace elements in the development, pathogenesis, and progression of diabetes. They briefly report on the most important known processes of zinc(II), manganese(II, III), copper(I, II), chromium(III), iron(II, III), cobalt(II), vanadium(III, IV, V), molybdenum(IV, VI), iodine(I), selenium(II, IV, VI), and lithium(I) in the human body and the biochemical changes associated with diabetes. Differences in trace element status in diabetes, their relationship to free radicals, and the antioxidant defense system are detailed. Some risk factors that lead to more severe micronutrient deficiencies and complications are also discussed.

Immobilization of Metronidazole on Mesoporous Silica Materials.

Metronidazole (MTZ) is a widely used drug, but due to its many side effects, there is a growing trend today to use a minimum dose while maintaining high efficacy. One way to meet this demand is to reduce the size of the drug particles. A relatively new method of size reduction is attaching the drug molecules to a mesoporous carrier. In this paper, we studied the fixation of MTZ molecules on mesoporous silica carriers. The drug was immobilized on two mesoporous silica materials (Syloid, SBA-15) with the use of a variety of immersion techniques and solvents. The immobilized drug was subjected to physicochemical examinations (e.g., SEM, XPS, XRD, nitrogen uptake, DSC) and dissolution studies. A significantly higher immobilization was attained on SBA-15 than on a Syloid carrier. Among the processing parameters, the type of MTZ solvent had the highest influence on immobilization. Ultrasonic agitation had a lower but still significant impact, while the concentration of MTZ in the solution made no difference. Under optimal conditions, with the application of an ethyl acetate solution, the surface coverage on SBA-15 reached as much as 91%. The immobilized MTZ exhibited a ca. 10% faster dissolution rate as compared to the pure micron-sized drug particles.

[Effects of magnesium supplementation on calcium and magnesium levels, and redox homeostasis in normolipidemic and food-induced hyperlipidemic rats]. / Magnéziumpótlás hatása a kalcium- és magnéziumszintekre, valamint a redox-homeosztázisra normolipidaemiás és alimentárisan eloidézett hyperlipidaemiás patkányokban.

UNLABELLED: Magnesium supplementation is quite popular because of intention of health and healthy lifestyle. However, there is no information on the metabolic effects of magnesium supplementation in healthy people and in different diseases. AIMS: Authors examined the effects of magnesium-malate on calcium, magnesium levels, and antioxidant parameters in normolipidemic and hyperlipidemic rats. METHODS: Male Wistar rats (n = 40; 150-200 g) were divided into 4 groups (control, control-treated, hyperlipidemic, hyperlipidemic-treated). Rats in the control and control-treated groups were fed with normal diet, while hyperlipidemic and hyperlipidemic-treated groups were fed with fat rich diet (2% cholesterol, 20% sunflower oil, 0.5% cholic acid). After the 9-day-long diet the following parameters were measured: routine laboratory parameters with automatic analysator, metal content using ICP-OES, and redox-parameters using spectrophotometric and luminometric methods. RESULTS: Magnesium-malate failed to produce significant changes in the measured parameters in control animals in most cases. Magnesium-malate decreased significantly serum glucose concentration, alkaline phosphatase and amylase activities in the hyperlipidemic group. Significantly low induced chemiluminescent activity was measured in the plasma and erythrocytes of hyperlipidemic group. The magnesium supplementation did not increase significantly magnesium concentration in different organs although the calcium/magnesium concentration ratio was decreased. CONCLUSIONS: In control animals there was no significant change in the measured parameters in most cases after dietary supplementation with a large amount of magnesium for a short period of time, but magnesium supplementation affected the metal homeostasis, routine laboratory parameters and redox system in hyperlipidemic animals. Although several changes were favorable, it should be emphasized that magnesium supplementation must be applied watchfully particularly in metabolic diseases.

Metronidazole does not show direct antioxidant activity in in vitro global systems.

Metronidazole has been widely used topically and systemically for more than 50 years but data on its antioxidant properties are still incomplete, unclear and contradictory. Its antioxidant properties are primarily hypothesized based on in vivo results, therefore, studies have been performed to determine whether metronidazole has antioxidant activity in vitro. We used so-called global spectrophotometric and luminometric methods. Fe3+/Fe2+-reducing ability, hydrogen donor activity, hydroxyl radical scavenging property and lipid peroxidation inhibitory activity were investigated. Under the condition used, metronidazole has negligible iron-reducing ability and hydrogen donor activity. The hydroxyl radical scavenging capacity cannot be demonstrated. It acts as a pro-oxidant in the H2O2/.OH-microperoxidase-luminol system, but it can inhibit the induced lipid peroxidation. According to our results, metronidazole has not shown antioxidant activity in vitro but can affect redox homeostasis by a ROS-independent mechanism due to its non-direct antioxidant properties.

Inhibition of lipid peroxidation of herbal extracts (obtained from plant drug mixtures of Myrtilli folium, Phaseoli fructus sine seminibus and Salviae folium) used in type 2 diabetes mellitus.

Plant drug mixtures are widely used in the adjuvant therapy of type 2 diabetes mellitus for the prevention of complications. The drug mixtures generally contribute to the efficiency of the therapy and may also reduce undesirable side effects. Two herbal extracts (lyophilized aqueous extracts of plant drug mixtures 1: Myrtilli folium, Phaseoli fructus sine seminibus and 2: Myrtilli folium, Phaseoli fructus sine seminibus, Salviae folium) were investigated in in vitro rat models. The content of bioactive constituents (polyphenol, flavonoid and vitamin C) in plant drug mixtures and lyophilized samples was evaluated. The antioxidant activity of lyophilized extracts was determined by measuring the ferric reducing ability of the plant, Fe2+ induced lipid peroxidation (LPO) in rat brain homogenates and NADPH (beta-nicotinamide adenine dinucleotide phosphate reduced form) induced LPO in cerebral microsomes. The antioxidant activity of lyophilized extracts was compared to that of quercetin and rutin. Both teas of lyophilized extracts had significant reducing ability (2694 and 2771 micromol/l) and inhibited LPO (IC50 28.0 and 20.6 microl in NADPH induced LPO, 17.3 and 8.7 microl in Fe2+ induced LPO). The high concentration of polyphenol/flavonoid (12.38-13.00 and 1.45-5.22 g/100 g, respectively) and vitamin C (0.099-0.165 g/100 g) in the herbal extracts is related to their significant antioxidant properties. The tea mixtures have significant nutritional value, since the consumption of 2 or 3 cups of tea a day covers 50% of the daily requirement of vitamin C and it is also relevant polyphenol source. The high polyphenol/flavonoid content may restore the redox imbalance and contribute to the prevention of diabetic complications.

[Effects of bioactive molecules of Beta vulgaris L. ssp. esculenta var. rubra on metastatic prostate cancer]. / A Beta vulgaris L. ssp. esculenta var. rubra bioaktív vegyületeinek hatása metasztatikus prosztatarákban.

UNLABELLED: Several reports are known about the effects of nutrition supplements in the improvement of quality of life of patients with tumor, however, the physiological background remains largely unknown. Table beet affects numerous biochemical reactions, enzymes and metabolic-synthesis. METHODS: Natural table beet product come from commercial service was given twice 10 g daily for 1 month for 24 patients (mean age 68+/-8 years) with hormone-resistant and metastatic prostate cancer treated with taxan chemotherapy, who report themselves first, mean 3,6+/-2,8 years ago with their complains. 18 men's data were amenable after treatment for evaluation. In addition to routine laboratory examination values of HbA1c, 9 cytokines and levels of 3 growth factors, the global parameters of redox-homeostasis, few elements of their metal-ions, Zn- and level of free protoporfirin, trans-metilating processes before and 1 month after treatment were determined. RESULTS: In most of the patients, favorable impact of beet was enforced and significantly high levels of Zn- and free protoporfirin decreased; furthermore, trans-metilating processes fastened. CONCLUSIONS: According to results, it seems that moderate and permanent consumption of table beet product affects the life expectancy of patients favorably; however, due to the increasing values of EGF, medical control is necessary for patients with prostate cancer treated by chemotherapy.

Fat rich diet-induced steatosis and changes in the gut­liver axis / A zsírdús étrend indukálta steatosis és a bél-máj tengely változásai.

INTRODUCTION: Fatty liver can develop as a result of diseases, surgical procedures, medicaments, malnutrition or excessive alcohol consumption, however, fat and poor fiber feeding can be attributed as the primary cause. Non-alcoholic fatty liver can be found in 20-30% of the population. Generally, alimentary-induced fatty liver in early state is described as uncomplicated liver injury. AIM: The aim of our research was to study the effect of fat rich nutrition on the gut-liver axis by routine laboratory, analytical and histological methods in rats. METHODS: We also examined the redox parameters of the liver and of the bowel. Fatty acid composition and element content of liver were measured. RESULTS: Significant changes were found in parameters of redox homeostasis as well as alterations in liver enzymes and metabolites. The changes could be detected in the liver, blood and bowel parts. The development of fatty liver is associated with the decrease of transmethylation capacity. Fatty acid composition and metal ion homeostasis were also altered in liver. Histological examinations showed that hepatocytes were swollen in the central part of the liver lobules, showed droplets and pycnotic nuclei, which were characterized by fatty degeneration. Small and large bowel enterocytes were damaged, sometimes pushed from the surface, and sometimes inflammatory reactions in the mucous membrane were observed. CONCLUSION: Our results suggest that alimentary fatty liver in early state is not considered simply as a reversible alteration because it alters the entire body's redox homeostasis and establishes heart and serious metabolic diseases as well as hasten the development of gastrointestinal tumors. Orv Hetil. 2020; 161(35): 1456-1465.

Impact of milk thistle (Silybum marianum) on the mycotoxin caused redox-homeostasis imbalance of ducks liver.

The Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEA) frequently contaminate grain crops, especially maize, the basis of poultry's feed. Mycotoxins enter the food chain and induce pathological changes in edible tissues. Milk thistle (Silybum marianum) has been used for the treatment of liver disease in humans because of its antioxidant and hepatoprotective effects, but its utility in veterinary use is poorly examined. To investigate possible protective properties against mycotoxin caused oxidative stress in poultry, pressed form of milk thistle seed (0.5%) was tested in white, female, Hungarian ducks over a feeding period of 47 days. Ducks were separated into 3 groups. The first group was fed with normal diet. The second group was fed with normal diet contaminated with DON (4.9 mg/kg) and ZEA (0.66 mg/kg). The third group received mycotoxin contaminated feed with milk thistle supplementation. Histological examination, markers of the redox status and metal element concentration measurements were carried out. The results showed alterations in the histological examination and in the redox homeostasis markers as a short-term effect by strengthening the antioxidant system. Acute exposure of mycotoxins caused an oxidative stress, which induced an effective antioxidant defensive response of the organism indicated by the free sulfhydryl group content (from 0.72 ± 0.06 to 0.77 ± 0.11) and the reducing power (0.49 ± 0.06 to 0.52 ± 0.08) elevation. The short-term free radical injury may be compensated by the liver resulting in decreased lipid peroxidation markers (malondialdehyde concentration: from 16.86 ± 0.49 to 0.94 ± 0.15, conjugated diene concentration: from 0.21 ± 0.07 to 0.17 ± 0.03). Silymarin further strengthtened the antioxidant defense by the elevation of sulfhydryl groups concentration and reducing power property resulted in decreased total scavenger capacity. However the concentration of lipid peroxidation markers were further elevated by the used antioxidant treatment (MDA: 5.2 ± 0.35, DC: 0.26 ± 0.08). In conclusion, the mycotoxin-contamination activated effectively the antioxidant system. The milk thistle supplementation has cytoprotective effects according to the histological findings, activated the antioxidant system, however the elevation of lipid peroxidation products need further explanation.

Metal element alteration in the lung by cisplatin and CV247 administration.

Despite significant nephrotoxicity, cisplatin is still used in the therapy of various tumors. We were interested in how metal ion composition is altered by cisplatin and whether platinum accumulates in the non-tumorous lung. We also aimed to study metal ion changes after treatment with a veterinary medicament CV247 with antioxidant property (containing Cu and Mn gluconate, ascorbic acid, Na salicylate), and whether CV247 alters pulmonary platinum accumulation in the healthy lung. Male Wistar rats were randomly selected into 4 groups (n = 10/group): control group, cisplatin-treated group, CV247-treated group, cisplatin + CV247-treated group. Inductively coupled plasma optical emission spectrometry and mass spectrometry were used for measuring Al, As, B, Ba, Ca, Cd, Co, Cu, Cr, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Pt, S, Sb, Se, Sn, Sr, and Zn in the lung and the redox state was measured in the plasma. Cisplatin influenced the element homeostasis in the lung. Pt, Mn, Se accumulation and Ca, Mg excretion were observed after treatment with cisplatin. The antioxidant CV247 supplementation modified the Mn concentration; however, the concentration of Cu did not change despite the Cu content of the product, and CV247 did not affect other metal concentrations in the lung of the cisplatin-treated group. In conclusion, cisplatin has a systemic impact on the metal element metabolism, and this effect was demonstrated in the healthy lung, too. The results indicate the importance of supplementing some essential elements, such as Ca and Mg during cisplatin cancer therapy.

[The role of zinc in the homeostasis of the human organism]. / A cink szerepe az emberi szervezet homeosztázisában.

The concentrations of essential metal ions in various compartments of the human body are accurately regulated (homeostasis). Irregularities in the accumulation or depletion of the trace elements may lead to well characterized diseases. This review covers the metabolism of zinc regulations by which the intracellular and extracellular levels are kept in physiological range, biological functions, as well as pathological states that develop in its altered metabolism. The focus is on the molecular mechanisms of zinc ion traffic between compartments of the body and cells and their sequestration, gene regulations that regulate the ion fluxes via biological membranes and their storage, zinc-mediated cell and tissue damages, and development of symptoms in zinc deficiency is also discussed.

[Metal element homeostasis and oxidative stress in pathological processes]. / Fémelem-homeosztázis és oxidatív stressz patológiás folyamatokban.

The author briefly summarizes the relationship between oxidative stress and changes in metal ion metabolism in pathological processes. Essential metal ions such as Ca, Mg, Fe, Cu, Zn, Se are essential in the living organisms, their metabolism and intracellular concentration are strictly regulated. Externally or intrinsically, altered metal ion metabolism can lead to metal ion accumulation or metal ion deficiency. Excess amounts of redox-active essential metals such as Fe, Cu, Co, Cr, Ni can induce free radicals under certain circumstances that cause inflammation, cell damage, and cancerous changes, although the molecular mechanism is still unclear in every detail. Changes in the metabolism of non-essential and non-variable valence metal ions also affect redox homeostasis. Despite the fact that each metal can react in a unique way and with different mechanisms, similar processes occur, where both metal deficiency and excessive metal induce oxidative stress. Antioxidant defense system is damaged, free radicals produced alter the redox balance, and redox homeostasis changed induces the production of cytokines and other transcription factors that affect the intracellular signaling pathways and affect the development of various diseases, including metabolic, cardiovascular, neurological diseases and cancer. Orv Hetil. 2019; 160(36): 1407-1416.

Oxidative stress with altered element content and decreased ATP level of erythrocytes in hepatocellular carcinoma and colorectal liver metastases.

Our aim was to study the possible alterations of redox status (enzymatic and nonenzymatic parameters and metal elements) in erythrocytes of patients with hepatocellular carcinoma (HCC), colorectal liver metastases (CRLM) and benign liver neoplasms. The function of redox homeostasis is closely connected to the energy level of erythrocytes, therefore, the ATP level was also determined. Antioxidant parameters, enzyme activities of superoxide dismutase and glutathione peroxidase were estimated in the erythrocytes of 11 patients with benign tumour, 23 patients with primary malignant and 37 metastatic liver tumour patients and 30 age-matched and sex-matched healthy controls. Element content with inductively coupled plasma optical emission spectrometer and ATP level by the chemiluminometric method were also determined from the samples. Free radical intensity was significantly increased, whereas erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly decreased in the HCC and CRLM groups versus benign groups and controls. Se, Mn and Zn levels were lowered in HCC and CRLM groups versus benign and control groups. The content of Cu, Mg, Se and Zn changed significantly between HCC and CRLM groups. Similarly, ATP concentration decreased in HCC and CRLM versus controls and benign groups. The lowest levels of ATP and antioxidant enzyme activities were found in the case of CRLM patients. These results reveal an alteration in the ATP level of erythrocytes with concomitant changes in the antioxidant defence system in hepatic cancer patients. Altered redox homeostasis (oxidative damage) may lead to decreased ATP level and consequently may play an important role in primary carcinogenesis and generation of metastases, as well.

Metal- and redox homeostasis in prostate cancer with vitamin D3 supplementation.

Vitamin D3 supplementation has a beneficial effect on cancerous patients, although it can influence the redox- and metal homeostasis. The aim of our investigation was to demonstrate the effect of vitamin D3 consumption on the redox- and metal homeostasis in prostate cancer, because of the recommended daily dose increased from 200 IU to 2000 IU in recent years in Hungary. Forty-three volunteers were involved in the study. The grouping was applied according to the clinical routine laboratory parameters (vitamin D3) and the tumor markers (PSA, fPFA). Patients were divided into 5 groups: (A) patient control (N = 8), (B) patient control with vitamin D3 treatment (N = 9), (C) high-risk prostate cancer group (N = 6), (D) high-risk prostate cancer group with vitamin D3 treatment (N = 8) and (E) vitamin D3 treated cancerous group with androgen deprivation therapy (N = 11). The element concentrations were determined with ICP-OES. Among the redox parameters, free radical scavenging capacity and H-donating ability were determined with luminometry and spectrometry. Vitamin D3 treatment caused differences in the metal- and redox homeostasis in either patient control and cancerous groups. The concentration of Fe, Cr, and Pb significantly increased in the erythrocytes of prostate cancer patients. According to the higher scavenging capacity by vitamin D3 treatment, it seems that vitamin D3 helps to equilibrate the redox homeostasis that could affect the outcome of cancer positively. However, the tendency in the metal element status does not give a clear explanation of cancer's outcome, but the accumulation of Pb by vitamin D3 supplementation needs to be taken into more serious consideration in set terms of occupational diseases.