Hepatotoksični potencijal smeše toluena, stirena i etanola: in silico toksikogenomička analiza

Organic solvents are still widely used in various industries and considered the most common chemicals associated with liver injury in workers. For research into the relationships between these chemicals and genes, interactions among chemicals, molecular pathways and biological processes, a significant place in toxicity testing has been taken by in silico methodologies. This study aims to provide evidence for the involvement of a selected mixture of organic solvents (toluene, styrene, ethanol) in liver disease development and show the potential of in silico toxicogenomic data-mining in determining possible mechanisms of mixture toxicity. The Comparative Toxicogenomics Database (CTD), GeneMania and ToppGene Suite were used for data-mining. The results showed that there were 17 genes connected with liver injury common for all the tested solvents. Co-expression (61.73%) was the most prominent interaction between the genes, while physical interactions were present at 14.56%, co-localization at 12.54% and interactions predicted by the server at 6.62%. Gene ontology analysis revealed biological processes affected by the investigated mixture (reactive oxygen species metabolic and biosynthetic process, response to oxidative stress, and response to organic cyclic compound). Oxidative stress response, antioxidant and oxidoreductase activity, vitamin B12 metabolism were noted as the key molecular pathways contributing to liver disease development. Our results emphasize the role of oxidative stress as one of the mechanisms of organic solvents' mixture toxicity and provide new insights into molecular mechanisms involved in hepatotoxicity.Organski rastvarači se još uvek široko koriste u raznim industrijama i smatraju se najčešćim hemikalijama povezanim sa oštećenjem jetre kod radnika. Za istraživanje odnosa između ovih hemikalija i gena, interakcija među hemikalijama, molekularnih puteva i bioloških procesa, značajno mjesto pripada i in silico metodologijama. Cilj ove studije je da pruži dokaze za povezanost odabrane smeše organskih rastvarača (toluen, stiren, etanol) u razvoju bolesti jetre, i da pokaže potencijal in silico toksikogenomičke analize podataka u određivanju mogućih mehanizama toksičnosti smješe. Za prikupljanje podataka korišteni su Comparative Toxicogenomics Database (CTD), GeneMania i ToppGene Suite. Rezultati ove analize su pokazali da postoji 17 gena povezanih s oštećenjem jetre zajedničkih za sva tri navedena rastvarača. Koekspresija (61,73%) bila je najistaknutija interakcija između gena, dok su fizičke interakcije bile prisutne sa 14,56%, kolokalizacije sa 12,54%, a interakcije predviđene od strane servera sa 6,62%. Analiza ontologije gena izdvojila je biološke procese na koje utiče ispitivana smeša (metabolički i biosintetski proces reaktivnih kiseonikovih vrsta, odgovor na oksidativni stres i odgovor na organska ciklična jedinjenja). Odgovor na oksidativni stres, aktivnost antioksidanata i oksidoreduktaze, i metabolizam vitamina B12 su navedeni kao ključni molekularni putevi koji dobrinose razvoju bolesti jetre. Rezultati ovog rada naglašavaju ulogu oksidativnog stresa kao jednog od mehanizama toksičnosti smeše organskih rastvarača i daju novi uvid u molekularne mehanizme uključene u hepatotoksičnost.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Povećani oksidacijski stres u obućarskih radnika izloženih mješavini niskih razina hlapljivih organskih spojeva

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 occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2•-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.Cilj istraživanja bio je procijeniti redoks status i koncentracije metala u tragovima kod 49 radnika (11 muškaraca i 38 žena) zaposlenih u industriji obuće, izloženih mješavini hlapljivih organskih spojeva (engl. volatile organic compounds, krat. VOC) koju su činili alifatski i aromatični ugljikovodici, ketoni, esteri, eteri i karboksilne kiseline. Sve izmjerene razine VOC bile su ispod dozvoljenih granica profesionalne izloženosti. U kontrolnoj je skupini bilo 50 neizloženih ispitanika (25 muškaraca i 25 žena). U plazmi obućarskih radnika analizirani su sljedeći parametri: superoksid anion radikal (O2 •- ), uznapredovali produkti oksidacije proteina (AOPP), totalni oksidacijski status (TOS), prooksidacijsko- antioksidacijski balans (PAB), indeks oksidacijskoga stresa (OSI), aktivnost superoksid-dismutaze (SOD), aktivnost enzima paraoksonaze-1 (PON1), ukupni sadržaj sulfhidrilnih grupa (SHG) i totalni antioksidacijski status (TAS). Koncentracije metala u tragovima (bakar, cink, željezo, magnezij i mangan) analizirane su u punoj krvi. U usporedbi s kontrolnom skupinom, svi parametri oksidacijskoga stresa i antioksidacijske obrane u izloženih radnika bili su povišeni, osim aktivnosti PON1. Povećana koncentracija Fe, Mg i Zn te smanjena koncentracija Cu uočene su u izloženih muškaraca u usporedbi s kontrolnima, a u žena je primijećena povišena koncentracija Fe, a niža koncentracija Mg, Zn i Cu u odnosu na kontrolnu skupinu. Naši nalazi potvrđuju da kombinirano izlaganje mješavini VOC, čak i pri dozvoljenim koncentracijama, može dovesti do aditivnih ili sinergističkih štetnih učinaka na zdravlje i popratnih poremećaja. Trenutna procjena rizika, koja se uglavnom oslanja na učinke pojedinačnih kemikalija, izaziva zabrinutost i upućuje na potrebu za novim pristupima koji će objasniti kombiniranu izloženost većem broju kemikalija

SOIL – THE RESOURCE OF FUTURE

In this paper authors has researched utilization of land potentials in the world, Europe, Serbia and Montenegro and its ratio according to population. On the results of research authors remar that relation toward very important recurs are not satisfied at the global and national level. Permanent grow worlds population from one side and limited land from other side must be very seriously worning for the creators of the national governments and wider union of states that responsibility relation in initialization this resource

Oxidative stress parameters in workers exposed to a mixture of low-level organic solvents

Zaposleni u industriji obuće su potencijalno izloženi smješi organskih rastvarača, što predstavlja povećan rizik od hepatotoksičnosti, neurotoksičnosti i hematotoksičnosti. Toksičnost smješe se često može previdjeti, a još uvek nema dovoljno podataka o mehanizmima koji se aktiviraju u ljudskom organizmu uslijed profesionalne izloženosti niskim koncentracijama rastvarača. ...Employees in the shoe industry are potentially exposed to a mixture of organic solvents, which poses an increased risk of hepatotoxicity, neurotoxicity and hematotoxicity. The toxicity of the mixture can often be overlooked, and there are still uncertainties in occupational exposure to low concentrations of solvents regarding the mechanisms triggered in the human body. ..