Archives of Industrial Hygiene and Toxicology

Genotoxic and genoprotective effects of 1,4-dihydropyridine derivatives: a brief review

Elina Leonova — 2023-03-20

This review summarises current knowledge about the genotoxic and genoprotective effects of 1,4-dihydropyridines (DHP) with the main focus on the water-soluble 1,4-DHPs. Most of these water-soluble compounds manifest very low calcium channel blocking activity, which is considered "unusual" for 1,4-DHPs. Glutapyrone, diludine, and AV-153 decrease spontaneous mutagenesis and frequency of mutations induced by chemical mutagens. AV-153, glutapyrone, and carbatones protect DNA against the damage produced by hydrogen peroxide, radiation, and peroxynitrite. The ability of these molecules to bind to the DNA may not be the only mechanism of DNA protection, as other mechanisms such as radical scavenging or binding to other genotoxic compounds may take place and enhance DNA repair. These uncertainties and reports of high 1,4-DHP concentrations damaging the DNA call for further in vitro and in vivo preclinical research, pharmacokinetic in particular, as it can help pinpoint the exact mechanism(s) of the genotoxic and/or genoprotective action of 1,4-DHPs.

How different microfilters affect the recovery of eleven EU-regulated mycotoxins

Marija Kovač Tomas — 2023-03-28

Microfiltration is a common step in liquid chromatography – tandem mass spectrometry (LC-MS), a method of choice in determining several mycotoxins in a solution at once. However, microfiltration may entail filter-analyte interactions that can affect the accuracy of the procedure, and underestimate exposure. The aim of our study was to assess how five different membrane materials for syringe filters (nylon, polytetrafluoroethylene, polyethersulphone, mixed cellulose ester, and cellulose acetate) affect microfiltration and recovery of EU-regulated mycotoxins, including aflatoxins B1, B2, G1, and G2, deoxynivalenol, fumonisins B1 and B2, zearalenone, T-2 and HT-2 toxins, and ochratoxin A. Polytetrafluoroethylene filters turned out to least affect microfiltration through mycotoxin loss, followed by more commonly used nylon filters, whereas the remaining three filter membrane materials had such a negative effect on recoveries that we found them incompatible with the procedure. Our findings clearly suggest that it is important to select a proper filter type that suits analyte properties and solution composition and to discard the first few filtrate drops to ensure the accuracy of the analytical procedure.

New in vitro findings about halogenated boroxine cytotoxicity and deregulation of cell death-related genes in GR-M melanoma cells

Nikolina Elez Burnjaković — 2023-03-01

Anti-proliferative effects of halogenated boroxine – K₂(B₃O₃F₄OH) (HB) – have been confirmed in multiple cancer cell lines, including melanoma, but the exact mechanism of action is still unknown. This study aimed to determine its cytotoxic effects on human Caucasian melanoma (GR-M) cell growth in vitro as well as on the expression of cell death-related genes BCL-2, BECN1, DRAM1, and SQSTM1. GR-M and peripheral blood mononuclear (PBM) cells were treated with different HB concentrations and their growth inhibition and relative gene expression profiles were determined using the Alamar blue assay and real-time PCR. HB significantly inhibited cell growth of both GR-M and PBM cells but was even more effective in GR-M melanoma cells, as significant inhibition occurred at a lower HB concentration of 0.2 mg/mL. GR-M BCL-2 expression was significantly downregulated (P=0.001) at HB concentration of 0.4 mg/mL, which suggests that HB is a potent tumour growth inhibitor. At the same time, it upregulated BCL-2 expression in normal (PBM) cells, probably by activating protective mechanisms against induced cytotoxicity. In addition, all but the lowest HB concentrations significantly upregulated SQSTM1 (P=0.001) in GR-M cells. Upregulated BECN1 expression suggests early activation of autophagy at the lowest HB concentration in GR-M cells and at all HB concentrations in PBM cells. Our findings clearly show HB-associated cell death and, along with previous cytotoxicity studies, reveal its promising anti-tumour potential.

Different damaging effects of volatile anaesthetics alone or in combination with 1 and 2 Gy gamma-irradiation in vivo on mouse liver DNA: a preliminary study

Vesna Benković — 2023-03-15

As the number of radiotherapy and radiology diagnostic procedures increases from year to year, so does the use of general volatile anaesthesia (VA). Although considered safe, VA exposure can cause different adverse effects and, in combination with ionising radiation (IR), can also cause synergistic effects. However, little is known about DNA damage incurred by this combination at doses applied in a single radiotherapy treatment. To learn more about it, we assessed DNA damage and repair response in the liver tissue of Swiss albino male mice following exposure to isoflurane (I), sevoflurane (S), or halothane (H) alone or in combination with 1 or 2 Gy irradiation using the comet assay. Samples were taken immediately (0 h) and 2, 6, and 24 h after exposure. Compared to control, the highest DNA damage was found in mice receiving halothane alone or in combination with 1 or 2 Gy IR treatments. Sevoflurane and isoflurane displayed protective effects against 1 Gy IR, while with 2 Gy IR the first adverse effects appeared at 24 h post-exposure. Although VA effects depend on liver metabolism, the detection of unrepaired DNA damage 24 h after combined exposure with 2 Gy IR indicates that we need to look further into the combined effects of VA and IR on genome stability and include a longer time frame than 24 h for single exposure as well as repeated exposure as a more realistic scenario in radiotherapy treatment.

The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats

Antonija Vukšić — 2023-03-28

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.

A study on the relationship between sociodemographic characteristics and job stress and satisfaction among healthcare workers in Turkey during the COVID-19 pandemic

Hasan Tuna — 2023-02-23

The aim of this study was to determine the sociodemographic characteristics that affect job stress and job satisfaction in 454 healthcare workers (physicians, nurses, midwives, technicians, and other healthcare personnel) working with COVID-19 patients in primary healthcare institutions in Turkey with a cross-sectional, web-based survey between 9 and 30 August 2021. The survey included a personal information form, a standard job stress scale, and the Minnesota Satisfaction Questionnaire. The levels of job stress and job satisfaction did not differ between male and female respondents. Singles reported lower job stress and higher job satisfaction than the married respondents. Job stress did not differ between departments, but respondents on the front line who worked in a COVID-19 intensive care unit (ICU) (at any point and/or at the time of the study) or the emergency department reported lower job satisfaction than those working in other departments. Similarly, while stress did not differ by educational status, satisfaction of respondents with bachelor's or master's degree was lower than that of the rest. Our findings also suggest that working in a COVID-19 ICU and age are significant predictors of higher stress, whereas lower education, working in a COVID-19 ICU, and being married are good predictors of lower satisfaction. Further research should include other sociodemographic variables that may affect stress and satisfaction at work, and similar studies should follow up to see what was left in the wake of the pandemic.

Short-term effects of air pollution on hospital admissions for cardiovascular diseases and diabetes mellitus in Sofia, Bulgaria (2009–2018)

Angel Dzhambov — 2023-03-07

Bulgaria has a very high incidence of cardiometabolic diseases and air pollution-related mortality rate. This study investigated the relationship between daily air pollution levels and hospital admissions for ischaemic heart diseases (IHD), cerebral infarction (CI), and type 2 diabetes mellitus (T2DM) in Sofia, Bulgaria. We obtained daily data on hospitals admissions and daily average air pollution levels from 2009 to 2018. Pollutants of interest were particulate matter (PM_2.5 and PM₁₀), nitrogen dioxide (NO₂), sulphur dioxide (SO₂), ozone (O₃), and carbon monoxide (CO). Negative binomial regressions were fitted to study the effects of air pollution on hospital admission over the course of seven days prior to that event, accounting for autocorrelations and time trend in the data, day of the week, temperature, and relative humidity. Our findings confirm that higher air pollution levels generally increase the risk of hospital admissions for IHD and CI. For T2DM the association is less clear. Admissions often lagged several days behind and were more common in specific demographic subgroups or when pollution crossed a particular threshold. However, we did not expect to find the risk of hospital admissions increased in warmer rather than colder months of the year. Our findings are to be taken with reservation but do provide an idea about how air pollution could trigger acute episodes of related cardiovascular diseases, and our model may serve to investigate similar associations across the country.

Energy and emission properties of burley tobacco stalk briquettes and its combinations with other biomass as promising replacement for coal

Maja Malnar — 2023-02-20

As a tobacco producer, Serbia has to deal with large amounts of leftover tobacco stalks after harvesting. One option for this type of biomass is to burn it, but burning is not encouraged in Serbia, since the levels of its combustion products have not been investigated yet. The aim of this study was therefore to determine the elemental composition, ash and nicotine content, heat values, and composition of gaseous combustion products of tobacco stalk briquettes and to see if their mixing with other types of biomass available in Serbia could improve their ecological profile. We made 11 different types of briquettes: six of pure raw materials, including burley tobacco stalks, sunflower head remains, wheat straw, corncob, soy straw, and beech sawdust and five by mixing tobacco stalks with these other raw materials in a 50:50 mass ratio. All briquettes meet the ecological criteria regarding the emission limits for nitrogen oxides (NO_x), sulphur dioxide, carbon monoxide, and carbon dioxide. Nicotine content in flue gases (<10 mg/kg) is far below the maximum level allowed by the European Union. Heat values of all biomass samples are acceptable, although lower than those specified for solid biofuels (≥16.0 MJ/kg), save for corncob and beech sawdust and their mixtures with tobacco stalks. Our findings therefore encourage the use of tobacco stalks as a viable biofuel.