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Publications (101)
Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA))...
The aim of this study was to: (i) determine and compare the capacity of bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), bisphenol A (BPA), and their mixture to produce testicular toxicity after the subacute exposure; (ii) explore the mechanisms behind the observed changes using in silico toxicogenomic approach. Male rats were randoml...
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...
The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and 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 experi...
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...
This study aimed to explore the health impacts, mechanisms of toxicity, and key gene biomarkers of a mixture of the most prominent perfluoroalkyl/polyfluoroalkyl substances (PFAS) through in silico ADMET and toxicogenomic analysis. The following databases and tools were used: AdmetSAR (2.0), ADMETlab (2.0), Comparative Toxicogenomic Database, ToppG...
Even at low levels, exposure to ionising radiation can lead to eye damage. However, the underlying molecular mechanisms are not yet fully understood. We aimed to address this gap with a comprehensive in silico approach to the issue. For this purpose we relied on the Comparative Toxicogenomics Database (CTD), ToppGene Suite, Cytoscape, GeneMANIA, an...
COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed...
This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupat...
Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptos...
Simple Summary
Finding the best treatment for cancer remains one of the biggest scientific challenges in the 21st century. Available cancer treatments have issues like drug resistance and severe side effects, indicating the need for alternative therapies, especially for patients who do not respond well to regular methods like chemotherapy or surger...
The link between environmental pollution and obesity is of high importance, because understanding the relationship between the two can provide valuable insights into the complex factors contributing to the obesity epidemic. These chemicals, termed "obesogens," are believed to disrupt lipid metabolism processes, therefore promoting the development o...
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, fT...
The purpose of this study was to examine the impact of low doses of lead (Pb) on levels of thyroid hormones (T3, T4, Ft3, fT4) and thyroid related antibodies (anti-Tg and anti-TPO) in the rat model, and to genes that are related to Pb and thyroid function, relationships between genes, biological processes, molecular processes, and pathways using in...
The current study aimed to examine the effect of toxic metal(oid) mixtures (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), and nickel (Ni)) on female reproductive function in Wistar rats after the 28- and 90-day exposure to dose levels calculated on the basis of the previously conducted human study. Experimental g...
Recent data indicate that lead (Pb) can induce adverse effects even at low exposure levels. Moreover, the corresponding mechanisms of low Pb toxicity have not been well identified. In the liver and the kidneys, Pb was found to induce various toxic mechanisms leading to organ physiological disruption. Therefore, the purpose of the study was to simul...
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 Comparat...
Toxic metals (cadmium (Cd), lead (Pb), mercury (Hg) and arsenic (As)) and plastificators (bis (2 - ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA)) have been suggested to aid in colorectal carcinoma (CRC) advancement. Sulforaphane (SFN), isothiocyanate from cruciferous vegetables, diminishes chemical carcinogenesis susc...
Sulforaphane (SFN) is a naturally occurring molecule present in plants from Brassica family. It becomes bioactive after hydrolytic reaction mediated by myrosinase or human gastrointestinal microbiota. Sulforaphane gained scientific popularity due to its antioxidant and anti-cancer properties. However, its toxicity profile and potential to cause adv...
The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n=6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15mg Pb/kg bod...
The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles have received emergent authorization leading to global mass vaccinations. Al...
Environmentally relevant toxic substances may affect human health, provoking numerous harmful effects on central nervous, respiratory, cardiovascular, endocrine and reproductive system, and even cause various types of carcinoma. These substances, to which general population is constantly and simultaneously exposed, enter human body via food and wat...
The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme ACE2 and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes sho...
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...
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 d...
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 c...
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 individ...
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...
Considering that some researchers point to a possible influence of air pollution on COVID-19 transmission, severity, and death rate, the aim of our in silico study was to determine the relationship between the key air pollutants [sulphur dioxide (SO), carbon monoxide (CO), 2 particulate matter (PM x ), nitrogen dioxide (NO 2 ), and ozone (O 3 )] an...
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 pro...
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 begi...
Colorectal cancer (CRC) is a significant global health burden that ranks as the third most diagnosed and second most common cause of cancer related deaths worldwide. New therapeutic strategies include chemoprevention and use of molecules which could prevent, suppress or reverse CRC progression such as sulforaphane (SFN). However, evidences about it...
We aimed to examine the molecular basis of the positive effect of berberine against environmentally relevant toxic metal-linked Alzheimer's disease (AD). The Comparative Toxicogenomic Database (CTD) retrieved a set of genes common to lead, cadmium, methylmercury and arsenic linked to AD development and a set of genes through which berberine exerts...
Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial,...
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 car...
Mercury (Hg) is one of the most important environmental pollutants with endocrinedisrupting properties. There is little data from epidemiological studies describing the doseresponse relationship between toxic metal levels and hormone levels. The aim of this study was to use the nearest neighbor matching analysis to determine the difference in Hg co...
The aim of this study was to predict the molecular mechanisms and pathways of immunomodulator sulforaphane (SFN) against carcinoma using in silico toxicogenomic data mining. Three key tools applied in our analysis were Comparative Toxicogenomics Database (CTD; http://CTD.mdibl. org), ToppGene Suite portal (https://toppgene.cchmc.org) and Reactome K...
This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) was used as the main data mining tool, along with Ge...
This study aimed to: (i) determine the content of toxic metals and toxigenic fungi in 14 commercial herbal tea samples from the market of Belgrade, Serbia; and (ii) assess their risk to human health. After the microwave digestion (HNO3/H2O2, 7:1,v/v), toxic metal content was determined by graphite furnace atomic absorption spectroscopy (GF-AAS). Th...
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...
Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resistance to oxidants, serves as one of the key defensive factors against a range of pathological processes such as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals. An increase in human exposure to toxic metals via air, fo...
Considering the urgent need for novel therapeutics in ongoing COVID‐19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS‐CoV‐2 Main Protease (Mpro). To screen FDA‐appr...
This in silico toxicogenomic analysis aims to: (i) testify the hypothesis about the influence of the environmentally relevant toxic metals (lead, methylmercury (organic form of mercury), cadmium and arsenic) on molecular mechanisms involved in amyotrophic lateral sclerosis (ALS), Parkinson's Disease (PD) and Alzheimer's disease (AD) development; an...
While experimental animal investigation has historically been the most conventional approach conducted to assess drug safety and is currently considered the main method for determining drug toxicity, these studies are constricted by cost, time, and ethical approvals. Over the last 20 years, there have been significant advances in computational scie...
Cadmium (Cd), one of the most abundant environmental pollutants, is considered to have endocrine disrupting properties. However, data on the dose-response relationship between Cd dose and levels of hormones have been insufficiently studied, especially in human data sets. Thus, the aim of this study was to determine the possibility of analyzing data...
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, weigh...
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 ra...
Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological an...
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 treatmen...
div> Aims : An infectious disease (COVID-19) caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug...
This paper aims to present the importance of the benchmark dose (BMD) as a point of departure (the lowest dose or concentration in the experiment that deviates from the response that differs from the normal response) in toxicological risk assessment, as well as to present commonly used software for its calculation (BMDS and PROAST). Benchmark dose...
Cadmium (Cd), one of the most important environmental pollutants, can cause a number of toxic effects. These effects are the result of more than one mechanisms of toxicity, all interrelated in their complexity. Thus, it is difficult to identify a fine line between these mechanisms of Cd toxicity, making their understanding highly complicated. The m...
For over a century, one of the main toxicologists' goals was finding the relationship between the chemical structure and toxicity. The development of computer technologies has lead to the production of software models that could be applied for this purpose. However, use of in silico methodology in toxicology is very complex. Having in mind that tox...
