The aging kidney—as influenced by heavy metal exposure and selenium supplementation

The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50–60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.publishedVersio

Structural and Physico-Chemical Interpretation (SPCI) of QSAR Models and Its Comparison with Matched Molecular Pair Analysis

© 2016 American Chemical Society.This paper describes the Structural and Physico-Chemical Interpretation (SPCI) approach, which is an extension of a recently reported method for interpretation of quantitative structure-activity relationship (QSAR) models. This approach can efficiently be used to reveal structural motifs and the major physicochemical factors affecting the investigated properties. Its efficacy was demonstrated both on the classical Free-Wilson data set and on several data sets with different end points (permeability of the blood-brain barrier, fibrinogen receptor antagonists, acute oral toxicity). Structure-activity patterns extracted from QSAR models with SPCI were in good correspondence with experimentally observed relationships and molecular docking, regardless of the machine learning method used. Comparison of SPCI with the matched molecular pair (MMP) method clearly shows an advantage of our approach over MMP, especially for small or structurally diverse data sets. The developed approach has been implemented in the SPCI software tool with a graphical user interface, which is publicly available at http://qsar4u.com/pages/sirms-qsar.php

The Impact of Maternal Overweight on Hair Essential Trace Element and Mineral Content in Pregnant Women and Their Children

The aim of the present study was to investigate hair essential trace elements and mineral levels in 105 pregnant normal-weight (control) and 55 overweight and obese women in the third trimester of pregnancy, as well as in their children at the age of 9 months. The hair essential trace elements and mineral levels were assessed using inductively coupled plasma mass-spectrometry. Overweight pregnant women had significantly reduced Cr (- 24%; p = 0.047) and Zn (- 13%; p = 0.008) content, as well as elevated hair Na and K levels as compared to the controls. Children from overweight and obese mothers had lower hair Mo (- 18%; p = 0.017), Se (- 8%; p = 0.043), and V (- 24%; p = 0.028) levels, as well as elevated Sr content (19%; p = 0.025). Correlation analysis revealed a significant relationship between maternal and child hair levels of Co (r = 0.170; p = 0.038), Cu (r = 0.513; p < 0.001), Mn (r = 0.240; p = 0.003), and Na (r = 0.181; p = 0.027) in the whole sample. Pre-pregnancy maternal body mass index (BMI) positively correlated with maternal hair K (r = 0.336; p < 0.001) and Na (r = 0.212; p = 0.008) and negatively correlated with V (r = - 0.204; p = 0.011) and Zn (r = - 0.162; p = 0.045) levels. The results indicate that impaired trace element and mineral metabolism may play a role in the link between maternal obesity, complications of pregnancy and child's postnatal development. Hypothetically, dietary improvement may be used as a tool to reduce these risks. However, further experimental and clinical studies are required to investigate the relationship between obesity and trace element metabolism in pregnancy

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles

Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms. In view of the significant recent progress in research on TiO2NP neurotoxicity, the objective of the present study is to provide a narrative review on the molecular mechanisms involved in its neurotoxicity, with a special focus on the studies published in the last decade. The existing data demosntrate that although TiO2NP may cross blood-brain barrier and accumulate in brain, its neurotoxic effects may be mediated by systemic toxicity. In addition to neuronal damage and impaired neurogenesis, TiO2NP exposure also results in reduced neurite outgrowth and impaired neurotransmitter metabolism, especially dopamine and glutamate. TiO2NP exposure was also shown to promote α-synuclein and β-amyloid aggregation, thus increasing its toxicity. Recent findings also suggest that epigenetic effects and alterations in gut microbiota biodiversity contribute to TiO2NP neurotoxicity. Correspondingly, in vivo studies demosntrated that TiO2NPs induce a wide spectrum of adverse neurobehavioral effects, while epidemiological data are lacking. In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds. Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated

The effect of the Ti (IV)-citrate complex on Staphylococcus aureus growth and biofilm formation

The primary objective of this study was to investigate the influence of the Ti (IV)-citrate complex on growth dynamics and biofilm formation of S. aureus. Speciation analysis was performed in order to estimate the structure of the Ti complex existing in citrate solutions at near-physiological pH. It is estimated that the fully deprotonated tris(citrate) titanate ion [Ti(C6H4O7)3]8- predominates in solution at pH 6.46-7.44, and that this is most probably the biologically active form of Ti(IV)-citrate. In in vitro experiments, increasing concentrations of citric acid solutions (0.05, 0.005, 0.0005 M), served as positive controls, while the effects of respective concentrations of Ti(IV)-citrate were examined. The obtained results indicate that citrate decreased S. aureus 48 growth at all studied concentrations, whereas S. aureus 44 growth was decreased only by high concentrations of citrate (0.05M). Incubation of S. aureus culture with Ti(IV)-citrate significantly potentiated citrate-induced effects. Ti(IV)-citrate significantly altered specific bacterial growth rate in a similar manner. The most significant growth reduction was observed at the initial period of bacterial growth. At the same time, the opposite effect was detected in investigations of the effect of citrate and Ti(IV)-citrate on S. aureus biofilm formation. Citric acid suppressed S. aureus biofilm formation, whereas Ti(IV)-citrate displayed a significant stimulatory effect. Our findings suggest that Ti(IV)-citrate possesses a more pronounced biological effect than citrate. The proposed mechanism of this action is activation of complex transport into the cell and induction of oxidative stress. However, the exact mechanism of Ti(IV)-citrate biological action on bacterial cultures remains unknown

PREVENTIVE ZINC SUPPLEMENTATION EFFECT ON REDOX STATUS IN RAT MODEL OF MAFLD

Background. Oxidative stress plays an important role in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). Antioxidant trace elements as cofactors of antioxidant enzymes and metalloproteins are involved in this process. Zinc being an important antioxidant may have a positive effect on the treatment of liver pathology. The study aimed to assess the effect of preventive zinc supplementation on MAFLD in rats. Materials and Methods. A total of 26 three-month-old female Wistar rats were used in the present study. The activity of the antioxidant enzymes superoxide dismutase and catalase, some redox status markers, such as ceruloplasmin, oxidized tryptophan, dithyrosines, total thiols, carbonyls, TBARS, and uric acid were evaluated. Oxidative stress biomarkers were studied spectrophotometrically. Results. MAFLD was accompanied by hyperuricemia and a decrease in serum dityrosines. The addition of Zn to the diet prevented the development of steatosis, decreased the level of oxidized tryptophan in the liver, and paradoxically caused hyperuricemia in the MAFLD model used. Zn supplementation had a positive effect on the prevention of MAFLD, had a little effect on redox status of animals but caused paradoxical hyperuricemia. Future studies are needed to establish the mechanisms of the Zn effect at the cellular level

The impact of lifestyle factors on age-related differences in hair trace element content in pregnant women in the third trimester

BACKGROUND: Trace elements play a significant role in the regulation of human reproduction, while advanced age may have a significant impact on trace element metabolism. The objective of the present study was to assess the impact of lifestyle factors on age-related differences in hair trace element content in pregnant women in the third trimester. METHODS: A total of 124 pregnant women aged 20&ndash;29 (n = 72) and 30&ndash;39 (n = 52) were ex- amined. Scalp hair trace element content was assessed using inductively coupled plasma mass spectrometry at NexION 300D (Perkin Elmer, USA) after microwave digestion. RESULTS: The results showed that the elder pregnant women had 36% (p = 0.009), 14% (p = 0.045), and 45% (p = 0.044) lower hair Zn, V, and Cd content, and 16% (p = 0.044) higher hair B levels &ndash; in comparison to the respective younger group values. Multiple regression analysis demonstrated that the age of the women had a significant influence on hair V and Zn levels. B content was also significantly influenced by age at first intercourse, smoking status, and specific dietary habits. None of the lifestyle factors were associated with hair Cd content in pregnant women. Hair V levels were also affected by following a special diet. Interestingly, alcohol intake did not have a significant impact on hair trace element content. CONCLUSIONS: These data indicate that lifestyle factors have a significant influence on age-related changes in hair trace elements during pregnancy that may impact the outcome of pregnancy

Hypobaric hypoxia in treatment of metabolic menopausal syndrom

The aim of the research was to evaluate effectiveness of intermittent hypobaric hypoxic adaptation (IHHA) in treatment menopausal metabolic syndrome. The technique hypobaric hypoxia in a pressure chamber 'Ural -1 ‘ at simulated altitude of 3500 m (460 mm.Hg.) 22 three hours IHHA daily session course is used at treatment of 68 women (mean age 52,8+1,1) with metabolic menopausal syndrome. Influence of the given not medicamentous method of treatment on clinical displays menopausal syndrome, weight of a body, a level hormones, parameters lipid and a carbohydrate exchange was estimated. Om completion of the IHHA course redused modified menopause index by 39,9%, systolic arterial pressure by 13,4% and diastolic arterial pressure by 7,3%, body mass decrease by 6,1%. Follicle stimulating hormone and luteinizing hormone levels to decrease by 33,1 % and 27,8% accordingly. Estradiol level and degidroepiandrosteron increase by 15,2% and 17,2% accordingly; reduction of total holesterol by 19,5%, glucosae by 21,3%, insulin by 20,2%. In result high efficiency of use of a method of adaptation to periodic hypoxia in correction of metabolic infringements in postmenopause is revealed.Цель работы - выявить эффективность метода адаптации к периодической барокамерной гипоксии в лечении менопаузального метаболического синдрома. Использован метод адаптации к гипобарической гипоксии в барокамере «Урал-1»: 22 трехчасовых сеанса, проводимых ежедневно на «высоте» 3500 метров (460 мм.рт.ст.) в лечении 68 женщин (средний возраст 52,8+1,1) с менопаузальным метаболическим синдромом. Оценивалось влияние данного немедикаментозного метода на клинические проявления менопаузального синдрома, массу тела, уровень гормонов, показатели липидного и углеводного обмена. В результате адаптации к периодической барокамерной гипоксии выявлено снижение модифицированного менопаузального индекса на 39,9%, массы тела на 6,1%, систолического АД на 13,4% и диастолического АД на 7,3%. Уменьшился уровень фолликулостимулирующего и лютеинизирующего гормонов на 33,1 % и 27,8% соответственно, повысился уровень эстрадиола и дегидрозпиандростерона-сульфата на 15,2% и 17,2% соответственно; снизился уровень холестерина на 19,5%, глюкозы на 21,3%, инсулина на 20,2%. В результате исследования выявлена эффективность метода адаптации к периодической барокамерной гипоксии в коррекции метаболических нарушений у женщин в постменопаузе

Hypobarotherapy in correction clinical disorders of menopausal syndrom in women with natural and surgical menopause

The aim of the research was to evaluate effectiveness of hypobarotherapy in comparison with hormonal replacement therapy (HRT) in correction clinical disturbances in 216 women with menopausal syndrom. The technique hypobaric hypoxia in a pressure chamber 'Ural -1 ' at simulated altitude of 3500 m (460 mm.Hg.) 22 three hours daily session course is used at treatment women with different type of menopause (natural and surgical menopause). Influence of the given not medicamentous method of treatment, hormonal replacement therapy and complex therapy (hypobarotherapy and HRT) on clinical symptoms of menopausal syndrome in women with different type of menopause was estimated. In result high efficiency of use of a method of hypobarotherapy in correction clinical disturbances in women with natural menopause is revealed.С целью оценки эффективности гипобарической гипокситерапии в коррекции менопаузальных симптомов в сравнении с заместительной гормональной терапией (ЗГТ) проведено обследование 216 женщин с менопаузальным синдромом, разделенных в зависимости от вида менопаузы и варианта лечения на 6 групп. Курс гипобарической гипокситерапии в барокамере «Урал-1» (22 ежедневных трехчасовых сеанса) проведен в группах женщин с естественной и хирургической менопаузой. Оценивалось влияние данного немедикаментозного метода лечения, заместительной гормональной терапии и комплексного лечения (гипобаротерапии и ЗГТ) на клинические проявления менопаузального синдрома. В результате выявлена высокая эффективность гипобаротерапии в коррекции менопаузальных симптомов у женщин с естественной менопаузой