•Results on parameters of oxidative stress in blood, liver and kidney in Pb and/or Cd intoxication were presented.•Both Pb and Cd induce generation of reactive species and depletion of antioxidant ...defense system.•Pb and Cd mixture also causes oxidative stress induction indicating both antagonism and synergism between these two metals.
Besides being important occupational hazards, lead and cadmium are nowadays metals of great environmental concern. Both metals, without any physiological functions, can induce serious adverse health effects in various organs and tissues.
Although Pb and Cd are non-redox metals, one of the important mechanisms underlying their toxicity is oxidative stress induction as a result of the generation of reactive species and/or depletion of the antioxidant defense system. Considering that the co-exposure to both metals is a much more realistic scenario, the effects of these metals on oxidative status when simultaneously present in the organism have become one of the contemporary issues in toxicology.
This paper reviews short and long term studies conducted on Pb or Cd-induced oxidative stress in blood, liver and kidneys as the most prominent target organs of the toxicity of these metals and proposes the possible molecular mechanisms of the observed effects. The review is also focused on the results obtained for the effects of the combined treatment with Pb and Cd on oxidative status in target organs and on the mechanisms of their possible interactions.
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 water, but also by inhalation and dermal contact, while accumulating evidence suggests that probiotic cultures are able to efficiently adsorb and/or degrade them. Cell wall of probiotic bacteria/fungi, which contains structures such as exopolysaccharide, teichoic acid, protein and peptidoglycan components, is considered the main place of toxic substances adsorption. Moreover, probiotics are able to induce metabolism and degradation of various toxic substances, making them less toxic and more suitable for elimination. Other probable in vivo protective effects have also been suggested, including decreased intestinal absorption and increased excretion of toxic substances, prevented gut microbial dysbiosis, increase in the intestinal mucus secretion, decreased production of reactive oxygen species, reduction of inflammation, etc. Having all of this in mind, this review aims to summarize the state-of-the-art knowledge regarding the potential protective effects of different probiotic strains against environmentally relevant toxic substances (mycotoxins, polycyclic aromatic hydrocarbons, pesticides, perfluoroalkyl and polyfluoroalkyl substances, phthalates, bisphenol A and toxic metals).
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•Probiotic cultures are able to bind/degrade various toxic substances.•Probiotics decrease intestinal absorption/increase excretion of toxic substances.•Probiotics prevent gut microbial dysbiosis and increase intestinal mucus secretion.•Probiotics decrease oxidative stress and inflammation.•Multi-strain probiotics are proposed for removal of toxic substances mixtures.
Discovered in late 1817, cadmium is currently one of the most important occupational and environmental pollutants. It is associated with renal, neurological, skeletal and other toxic effects, ...including reproductive toxicity, genotoxicity, and carcinogenicity. There is still much to find out about its mechanisms of action, biomarkers of critical effects, and ways to reduce health risks. At present, there is no clinically efficient agent to treat cadmium poisoning due to predominantly intracellular location of cadmium ions. This article gives a brief review of cadmium-induced oxidative stress and its interactions with essential elements zinc and magnesium as relevant mechanisms of cadmium toxicity. It draws on available literature data and our own results, which indicate that dietary supplementation of either essential element has beneficial effect under condition of cadmium exposure. We have also tackled the reasons why magnesium addition prevails over zinc and discussed the protective role of magnesium during cadmium exposure. These findings could help to solve the problem of prophylaxis and therapy of increased cadmium body burden.
Iako je otkriven tek 1817. godine, kadmij je trenutačno jedan od najvažnijih onečišćivača životne i radne sredine. Štetno djeluje na bubrege, živčani sustav, kosti, reproduktivni sistem, a ima i genotoksične i karcinogene efekte. Nužna su dalja istraživanja vezana za mehanizme njegove toksičnosti, biomarkere efekata, kao i načine smanjenja rizika za zdravlje. Osim toga, do danas nije otkriven agens efikasan u terapiji trovanja kadmijem s obzirom na to da je kadmij intracelularni kation. U ovom radu dan je sažet pregled važnih mehanizama toksičnosti kadmija, kao što su nastanak oksidativnog stresa i interakcije s esencijalnim elementima, cinkom i magnezijem, na osnovi dostupnih literaturnih podataka, kao i naših ispitivanja koja upućuju na to da povećani unos navedenih esencijalnih elemenata pokazuje pozitivne efekte pri ekspoziciji kadmiju. Obrazložena je prednost suplementacije magnezijem pred suplementacijom cinkom i razmatrana preventivna uloga magnezija pri intoksikaciji kadmijem. Ovi su rezultati doprinos rješavanju problema profilakse i terapije trovanja kadmijem.
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 most important mechanisms by which Cd manifests its toxic effects include changes in gene expression and inhibition of damaged DNA repair, interference of apoptosis and autophagy, oxidative stress, and interaction with bioelements. In this review, we will give a brief overview of the recent developments and findings on the most relevant general and specific mechanisms and molecular pathways of Cd toxicity.
•Cadmium causes a number of toxic effects by various mutually linked mechanisms.•Cd interferes with genes and inhibits DNA damage repair.•Autophagy following Cd exposure can either suppress or activate apoptosis.•Apoptosis and autophagy can be induced by increased accumulation of ROS.•Cd generates ROS affecting antioxidant defense and/or bioelements levels.
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•207 men - metals (Cd, As, Hg, Ni, and Cr) + hormones (testosterone, LH, FSH) analysis.•The highest median and geometric mean for Ni, followed by Hg.•Dose-response relationship ...between all measured metals and hormones - confirmed.•The narrowest BMDI was found for Cd-testosterone and Hg-LH pairs.•BMD approach - significant in the dose–response analysis of human data.
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.
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.
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•An explicit dose-response dependency between hormone and BLL was evident.•Derived BMDLs for insulin were 1.49 (males) and 0.74 μg Pb/dL (females).•Pb threshold established for its endocrine effects might be very low.•The results provide new insight into human health risk assessment of low Pb exposure.
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
...approach to the issue. For this purpose we relied on the Comparative Toxicogenomics Database (CTD), ToppGene Suite, Cytoscape, GeneMANIA, and Metascape to identify six key regulator genes associated with radiation-induced eye damage (
,
,
,
,
, and
), all of which have physical interactions. Some of the identified molecular functions revolve around DNA repair mechanisms, while others are involved in protein binding, enzymatic activities, metabolic processes, and post-translational protein modifications. The biological processes are mostly centred on response to DNA damage, the p53 signalling pathway in particular. We identified a significant role of several miRNAs, such as hsa-miR-183 and hsamiR-589, in the mechanisms behind ionising radiation-induced eye injuries. Our study offers a valuable method for gaining deeper insights into the adverse effects of radiation exposure.
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 its safety in CRC patients are still lacking. The aim of this in silico investigation was to predict SFN-induced adverse effects in CRC patients by computational analysis. The study showed that 334 genes were consistently dysregulated in CRC (223 downregulated and 111 upregulated), while 38 were recognized as significant and might be used as predictive biomarkers for overall survival and metastasis (TCGA, GEO, R studio). Among them, SFN interacted with 86 genes, out of which 11 were marked as significant (correlate with overall prognosis and metastasis). Sulforaphane potentiates the overexpression of TIMP1, AURKA, and CEP55, and promotes inhibition of CRYAB, PLCE1, and MMP28, that might lead to the progression of CRC (CTD). Pathway enrichment analysis revealed that SFN stimulated Transcriptional activation of RUNX2, AURKA activation by TPX2, IL-10 signaling, while inhibited Differentiation of White and Brown Adipocyte process, an underlying pathway which inactivation led to obesity (Cytoscape ClueGo + CluePedia, DAVID). Thus, genome signature of CRC patients could serve as important factor when addressing the risk-to-benefit profile of SFN. Patients with colon cancer and increased expression of TIMP1, CCL20, SPP1, AURKA, CEP55, NEK2, SOX9 and CDK1, or downregulation of CRYAB, PLCE1, MMP28, BMP2 and PLAC8 may not be ideal candidates for SFN chemoprevention.
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•334 genes were dysregulated in colorectal carcinoma.•38 genes were in correlation with overall survival or metastasis.•SFN interacts with 86 differently expressed genes and 11 significant genes.•SFN potentiates TIMP1, AURKA, CEP55 expression and CRYAB, PLCE1, MMP28 inhibition.•Genome signature of CRC patients might impact the safety of SFN.
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
toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (
) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.
► Cadmium given peros or i.p. induces oxidative stress in liver of rats. ► Cadmium given i.p. induces more pronounced adverse effects. ► Magnesium co-treatment has beneficial effect on parameters of ...oxidative stress. ► Oral Mg administration reversed all Cd-affected parameters of oxidative stress. ► Both Cd and Cd+Mg effects on parameters of oxidative stress are route-dependent.
The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30mg Cd/kg b.w.)/Cd+Mg (30mg Cd/kg b.w., 50mg Mg/kg b.w.) or i.p. dose of Cd (1.5mg Cd/kg b.w.)/Cd+Mg (1.5mg Cd/kg b.w., 3mg Mg/kg b.w.) and sacrificed after 24h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent.
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