Nickel as a potential disruptor of thyroid function: benchmark modelling of human data.

Introduction: Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept. Methods: Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results. Results and discussion: The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances.

In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether.

The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms - oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research.

Exploring the endocrine disrupting potential of lead through benchmark modelling - Study in humans.

Exposure to low levels of a toxic metal lead (Pb) affects human health, and its effect as an endocrine disruptor has been reported. However, the precise role of Pb in endocrine health is still unclear because no dose-response relationship has been established for such an effect. The present study aimed to examine blood Pb levels (BLLs) in relation to serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and insulin in 435 nonoccupationally exposed Serbian subjects (218 women, 217 men, 18-94 years of age, mean age 48). In addition, benchmark dose (BMD) values were calculated for these endocrine endpoints using the PROAST 70.1 software. An explicit dose-response dependency between BLL and TSH, fT3, fT4, testosterone, and insulin serum levels was evident from BMD modelling. The results support the positive association between BLLs and serum insulin levels, with observed dose-response and calculated BMD values of 1.49 and 0.74 µg Pb/dL in males and females, respectively. Collectively, our findings reported potential endocrine-disrupting effects of Pb at the environmental exposure levels experienced by current Serbian population. They also strengthen the notion that the blood Pb threshold level for an endocrine effect is low.

Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A.

Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).

Fluoride subacute testicular toxicity in Wistar rats: Benchmark dose analysis for the redox parameters, essential elements and DNA damage.

Excessive fluoride (F-) levels in the environment could induce different pathological changes, including comorbidities in reproductive functions. Hence, the aim of the present in vivo study was to explore F- subacute toxicity mechanisms via Benchmark dose (BMD) methodology on rat's testicles. The experiment was conducted on thirty male Wistar rats for 28 days, divided into six groups (n = 5): 1) Control (tap water); 2) 10 mg/L F-; 3) 25 mg/L F-; 4) 50 mg/L F-; 5) 100 mg/L F-; 6) 150 mg/L F-. Testicles were dissected out and processed for the determination of F- tissue concentrations, redox status parameters, essential elements level, and DNA damage. PROASTweb 70.1 software was used for determination of external and internal dose-response relationship. The results confirmed a significant increase in superoxide anion (O2.-), total oxidative status (TOS), copper (Cu), zinc (Zn), iron (Fe), DNA damage levels, and decrease in superoxide dismutase activity (SOD1) and total thiol (SH) groups. The dose-dependent changes were confirmed for SOD1 activity and DNA damage. The most sensitive parameters were SOD1 activity and DNA damage with the lowest BMDLs 0.1 µg F-/kg b. w. Since human and animal populations are daily and frequently unconsciously exposed to F-, this dose-response study is valuable for further research regarding the F- health risk assessment.

Puzzling relationship between levels of toxic metals in blood and serum levels of reproductive hormones: Benchmark dose approach in cross-sectional study.

Reproductive disorders and infertility have become more common recently among the general population. Toxic metals are known as endocrine disruptors and as they are widespread in nature they may be linked to reproductive problems. This study was conducted as a cross-sectional study and its aim was to examine the dose-response relationship between cadmium, arsenic, mercury, chromium and nickel and serum hormone levels of testosterone (women) and estradiol and progesterone (men) using the Benchmark dose approach (BMD). Blood samples were collected from 218 women and 217 men digested in a microwave, and the levels of the tested metals were determined by atomic absorption spectrophotometry (AAS) or inductively coupled plasma-mass spectrometry (ICP-MS). Dose-response analysis was performed in PROAST software (version 70.1). The model averaging method was used to calculate the Benchmark dose interval (BMDI). A dose-response relationship has been established between all metals and hormones. The narrowest BMDI was found for the As-testosterone and Hg-testosterone. Levels estimated to produce the extra risk of testosterone serum levels disturbances of 10% were lower than median levels measured in the general population. Moreover, this research suggests the possibility of use of the BMD approach in analyzing data pool generated from extensive human-biomonitoring studies.

Redox and biometal status in Wistar rats after subacute exposure to fluoride and selenium counter-effects.

This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals [copper (Cu), iron (Fe), and zinc (Zn)] in the blood, liver, kidney, brain, and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F-) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutions ad libitum for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O2 .-) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O2 .- in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F- toxicity.

Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor.

The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) µg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.

Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: Data set from human study.

The main objective of this research was to conduct a dose-response modeling between the internal dose of measured blood Cd, As, Hg, Ni, and Cr and hormonal response of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The study included 207 male participants from subjects of 5 different cohorts (patients with prostate, testicular, and pancreatic cancer, patients suffering from various thyroid and metabolic disorders, as well as healthy volunteers), enrolled from January 2019 to May 2021 at the Clinical Centre of Serbia in Belgrade, Serbia. Benchmark dose-response modeling analysis was performed with the PROAST software version 70.1, showing the hormone levels as quantal data. The averaging technique was applied to compute the Benchmark dose (BMD) interval (BMDI), with benchmark response set at 10%. Dose-response relationships between metal/metalloid blood concentration and serum hormone levels were confirmed for all the investigated metals/metalloid and hormones. The narrowest BMDI was found for Cd-testosterone and Hg-LH pairs, indicative of high confidence in these estimates. Although further research is needed, the observed findings demonstrate that the BMD approach may prove to be significant in the dose-response modeling of human data.

Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis.

Lead (Pb) is a toxic metal that affects almost all human's system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.

Possible role of lead in breast cancer - a case-control study.

Numerous risk factors have been associated with breast cancer (BC), exposure to metalloestrogen, like lead, being such. Since lead involvement in BC is still equivocal, we focused on lead levels in three compartments of BC patients, blood, healthy, and malignant tissues. Also, as the cholesterol role in cancer development was recognized at the beginning of the twentieth century and led to involvement in lipid profile impairment, we further extend our research on lipid profile and enzymes responsible for maintaining lipid balance in BC patients. Fifty-five women diagnosed with BC were enrolled in the study. Forty-one healthy women represented the control group. Lead levels in blood, healthy surrounding and malignant tissue, and lipid profile parameters in serum, were determined. Higher lead levels were obtained in surrounding healthy tissue samples compared to cancerous tissue samples, while blood lead levels of BC women did not differ significantly from the control group. The altered lipid profile scheme in women diagnosed with breast cancer contained significantly higher triglycerides levels (P < 0.001). Moreover, logistic regression analysis revealed triglycerides as a significant predictor of BC (OR = 2.6; P < 0.01). Although statistical significance was missing for lower paraoxonase-1 (PON-1) activities observed in BC women, multivariate logistic regression singled out PON-1 activities as significant BC predictors. The result of the present study further indicated oxidative status imbalance and tissue levels bioelements perturbation. Obtained results in the present study propose possible lead involvement in BC onset accompanied with bioelements redistribution and oxidative stress occurrence.

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.

Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling.

Exposure to toxic metals, including lead (Pb), were found as important risk factor for cardiovascular diseases. The aim of the study was to simulate low-level subacute Pb exposure scenario and to determine redox status, redox scores (OXY-score, damage score and protective score) and copper (Cu), zinc (Zn), iron (Fe) and manganese (Mn) levels in cardiac tissue of Wistar rats. Based on the obtained results we have established dose-toxic response relationship and derived Benchmark dose. The male Wistar rats were divided in seven groups (n = 6), six threated groups that received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, by oral gavage and control group. The results of the presented study demonstrated that Pb affect cardiac tissue by inducing production of superoxide anion radical (O2.-) and consequently raising malondialdehyde (MDA) levels. The positive trend in OXY-score and damage score were determined. Effect size analysis showed that the main toxic effects were oxidative damage and elevation of MDA. The lowest BMD was calculated for MDA (2.2e-0.6 mg Pb/kg b.w./day). Obtained BMD may be useful in further assessing point of departure in the human health risks assessment of low-level Pb exposure scenario.

Integrating in silico with in vivo approach to investigate phthalate and bisphenol A mixture-linked asthma development: Positive probiotic intervention.

The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) mixture-induced asthma development and test probiotic as a potential positive intervention. Comparative Toxicogenomics Database (CTD) and ToppGene Suite were used as the main tools for in silico analysis. In vivo 28-day experiment was conducted on rats - seven groups (n = 6): (1) Control: corn oil, (2) P: probiotic (8.78 * 108 CFU/kg/day); (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day; (6) MIX: DEHP + DBP + BPA; (7) MIX + P. Lungs, thymus and kidneys were extracted and prepared for redox status and essential metals analysis. By conducting additional in vitro experiment, probiotic phthalate and BPA binding ability was explored. There were 24 DEHP, DBP and BPA asthma-related genes, indicating the three most probable mechanisms - apoptosis, inflammation and oxidative stress. In vivo experiment confirmed that significant changes in redox status/essential metal parameters were either prominent, or only present in the MIX group, indicating possible additive effects. In vitro experiment confirmed the ability of the multy-strain probiotic to bind DEHP/DBP/BPA mixture, while probiotic administration ameliorated mixture-induced changes in rat tissue.

Oxidative stress, metallomics and blood toxicity after subacute low-level lead exposure in Wistar rats: Benchmark dose analyses.

Exposure to lead (Pb) is still rising concern worldwide, having in mind that even low-dose exposure can induce various harmful effects. Thus, in-depth knowledge of the targets of Pb toxicity and corresponding mechanisms is essential. In the presented study, the six groups (male Wistar rats, n = 6) received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, each day by oral gavage, while the control group received distilled water only. All animals were sacrificed 24 h after the treatment, and blood was collected for the analysis of hematological, biochemical, oxidative status and essential elements levels. An external and internal dose-response relationship was performed using PROASTweb 70.1 software. The results showed that low doses of Pb affect hematological parameters and lipid profile after 28 days. The possible mechanisms at examined Pb dose levels were a decrease in SOD, O2•- and Cu and an increase in Zn levels. The dose-dependent nature of changes in cholesterol, HDL cholesterol, O2.-, SOD, AOPP in serum and hemoglobin, Fe, Zn, Cu in blood were obtained in this study. The most sensitive parameters that were alerted are Cu blood levels (BMDL5: 1.4 ng/kg b.w./day) and SOD activity (BMDL5: 0.5 µg/kg b.w./day). The presented results provide information that may be useful in further assessing the health risks of low-level Pb exposure.

Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: Merging bioinformatics with in vivo analysis.

Linkage between bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA) co-exposure and type 2 diabetes mellitus (T2DM), as well as ability of multi-strained probiotic to reduce DEHP, DBP and BPA mixture-induced oxidative damage in rat pancreas were investigated. The Comparative Toxicogenomics Database, Cytoscape software and ToppGene Suite were used for data-mining. Animals were sorted into seven groups (n = 6): (1) Control group: corn oil, (2) P: probiotic: Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus plantarum LP 6595 + Lactobacillus plantarum HEAL9; (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day, and (6) MIX: 50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA; (7) MIX + P. Rats were sacrificed after 28 days of oral exposure. In silico investigation highlighted 44 DEHP, DBP and BPA mutual genes linked to the T2DM, while apoptosis and oxidative stress were highlighted as the main mechanisms of DEHP, DBP and BPA mixture-linked T2DM. In vivo experiment confirmed the presence of significant changes in redox status parameters (TOS, SOD and SH groups) only in the MIX group, indicating possible additive effects, while probiotic ameliorated mixture-induced redox status changes in rat pancreatic tissue.

Cadmium tissue level in women diagnosed with breast cancer - A case control study.

Breast cancer is at the forefront of female malignancy and the leading cause of cancer death among women. Gender, age, hormone therapy, smoking, exposure to endocrine disruptors and family history are significant breast cancer risk factors according to epidemiological data. Considering metalloestrogenic Cd property and a plethora of research work on hormone involvement in breast cancer the study aimed to determine Cd concentration in three compartments of breast cancer patients in relation to their blood hormone status. Further, as oxidative stress is a critical mechanism of Cd toxicity, the objective of this study was to determine potential changes in oxidative status homeostasis. The study enrolled 55 patients with breast cancer diagnosis and 41 healthy women with benign breast changes. Concentration of Cd was determined using graphite furnace atomic absorption spectrometry. Cadmium concentration in tumor tissue was significantly higher than control and almost four times higher than Cd concentration in the healthy surrounding tissue. Strong positive correlation was observed between Cd concentrations in changed breast tissue and FSH and LH levels, while the correlation was negative with estradiol level. Cancer patients had significantly increased blood total antioxidative status while total oxidative status did not significantly differ between study groups. The study revealed Cd implication in breast cancer onset following a significant odd ratio for Cd levels in changed tissue samples. Moreover, presented data confirmed sex hormone and oxidative status imbalance caused by Cd presence, closely related to cancer development.

Genotoxicity of fluoride subacute exposure in rats and selenium intervention.

The aims of this study were to: (i) examine the toxic effects of sodium fluoride (NaF) in blood, liver, spleen, and brain cells of Wistar rats after the subacute exposure; (ii) explore the potential protective properties of selenium (Se) against fluoride toxicity after the simultaneous administration. Twenty male Wistar rats, eight weeks old, weighing approximately 140-190 g, were divided into four experimental groups (n = 5) as follows: I control-tap water; II NaF 150 ppm; III NaF 150 ppm and Se 1.5 mg/L; IV Se 1.5 mg/L, and had available water with solutions ad libitum for 28 days. DNA damage detected by comet assay was confirmed in the liver, spleen, and brain cells, but not in blood. Selenium supplementation together with NaF decreased DNA damage in liver and spleen cells. According to the histological findings, no changes were observed in spleen and brain tissues after NaF administration. Unlike the observed Se protective effect on the DNA level, no significant reduction of liver tissue injury was observed after the NaF and Se treatment, resulting in mild inflammation. Data of this study suggest that DNA damage after NaF subacute exposure at moderately high concentration was reduced in liver and spleen cells due to Se supplementation, but a similar change was not seen in the brain.

Redox and essential metal status in the brain of Wistar rats acutely exposed to a cadmium and lead mixture.

Most Pb and Cd neurotoxicity studies investigate exposure to either of the toxic metals alone, while data on co-exposure are scarce. The aim of our study was to fill that gap by investigating acute combined effects of Pb and Cd on redox and essential metal status in the brain of Wistar rats. Animals were randomised in four groups of six to eight rats, which received 15 or 30 mg/kg of Cd, 150 mg/kg of Pb, or 150 mg/kg of Pb + 15 mg/kg of Cd by gavage. The fifth, control, group received distilled water only. Co-treatment with Pb and Cd induced significant increase in malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) compared to control and groups receiving either metal alone. This is of special importance, as MDA presence in the brain has been implicated in many neurodegenerative disorders. The groups did not significantly differ in Zn, Cu, Mn, and Fe brain levels. Our findings highlight the importance of metal mixture studies. Neurotoxicity assessments of single chemicals do not provide a real insight into exposure to mixtures in real life. Further research should look into interactions between these metals to reveal complex molecular mechanisms of their neurotoxicity.

Multi-strain probiotic ameliorated toxic effects of phthalates and bisphenol A mixture in Wistar rats.

Phthalates and bisphenol A, to which people are mainly exposed through food, interfere with the body's endocrine system, along with various other toxic effects. Literature data suggest that probiotic cultures might be able to decrease the adverse effects of toxic substances by various mechanisms. The aim of this study was to investigate if treatment with multi-strained probiotic could reduce the toxicity of phthalates and bisphenol A mixture in Wistar rats. Animals were divided into four experimental groups (n = 6): (1) Control (corn oil); (2) P (probiotic (8.78 * 108 CFU/kg/day): Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus planarum LP 6595+ Lactobacillus planarum HEAL9); (3) MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA); (4) MIX + P. Animals were euthanized after 28 days of daily oral gavage treatment; blood and organs were collected for further analysis. Probiotic reduced systemic inflammation and had protective effects on liver, kidneys, spleen, lipid status and serum glucose level. It almost completely annulled the changes in biochemical, hematological and hormonal parameters and mitigated changes in relative liver size, food consumption and organ histology. These results suggest considering multi-strained probiotics as a dietary therapeutic strategy against toxicity of the investigated mixture.