Goran Gajski - Academia.edu (original) (raw)

Papers by Goran Gajski

Toxins, Feb 29, 2024

Among the various natural compounds used in alternative and Oriental medicine, toxins isolated fr... more Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and Apis mellifera venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A2 (PLA2), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.

Journal of xenobiotics, Mar 13, 2024

Archives of toxicology, May 28, 2024

Molecules, 2023

The aim of this study was to test the phytotoxicity and mode of action of bisphenol A (BPA) on Al... more The aim of this study was to test the phytotoxicity and mode of action of bisphenol A (BPA) on Allium cepa using a multibiomarker approach. A. cepa roots were exposed to BPA in concentration range 0-50 mg L-1 for 3 days. BPA even in the lowest applied concentration (1 mg L-1) reduced root length, root fresh weight, and mitotic index. Additionally, the lowest BPA concentration (1 mg L-1) decreased the level of gibberellic acid (GA3) in root cells. BPA at concentration 5 mg L-1 increased production of reactive oxygen species (ROS) that was followed by increase in oxidative damage to cells' lipids and proteins and activity of enzyme superoxide dismutase. BPA in higher concentrations (25 and 50 mg L-1) induced genome damage detected as an increase in micronucleus (MNs) and nuclear buds (NBUDs). BPA at >25 mg L-1 induced synthesis of phytochemicals. Results of this study using multibiomarker approach indicate that BPA is phytotoxic to A. cepa roots and has shown genotoxic potential to plants, thus its presence in the environment should be monitored.

Toxins, 2023

Envenomation by animal venoms remains a serious medical and social problem, especially in tropica... more Envenomation by animal venoms remains a serious medical and social problem, especially in tropical countries. On the other hand, animal venoms are widely used as a source of biologically active compounds for the development of novel drugs. Numerous derivatives of animal venoms are already used in clinical practice. When analysing the mechanisms of action of animal venoms, attention is usually focused on the main target of the venom's enzymes and peptides such as neurotoxic, cytotoxic or haemorrhagic effects. In the present review, we would like to draw attention to the "hidden" effects of animal venoms and their derivatives in regard to DNA damage and/or protection against DNA damage. Alkaloids and terpenoids isolated from sponges such as avarol, ingenamine G or variolin B manifest the capability to bind DNA in vitro and produce DNA breaks. Trabectidin, isolated from a sea squirt, also binds and damages DNA. A similar action is possible for peptides isolated from bee and wasp venoms such as mastoparan, melectin and melittin. However, DNA lesions produced by the crude venoms of jellyfish, scorpions, spiders and snakes arise as a consequence of cell membrane damage and the subsequent oxidative stress, whereas certain animal venoms or their components produce a genoprotective effect. Current research data point to the possibility of using animal venoms and their components in the development of various potential therapeutic agents; however, before their possible clinical use the route of injection, molecular target, mechanism of action, exact dosage, possible side effects and other fundamental parameters should be further investigated.

Toxics, 2024

Biomonitoring of human populations exposed to chemical substances that can act as potential mutag... more Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies.

Toxins, 2024

Journal of Xenobiotics, 2024

More than eight million premature deaths annually can be attributed to air pollution, with 99% of... more More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM10 exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure.

Arh Hig Rada Toksikol, 2024

Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs)... more Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia (Oreochromis mossambicus, Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.

European Journal of Radiology, Feb 1, 2021

It is known that the exposure to various environmental mutagens increase production of reactive o... more It is known that the exposure to various environmental mutagens increase production of reactive oxygen species (ROS). The increase of ROS production with the consequent disturbance of the oxidative balance in the cell, called oxidative stress, perturbs the metabolism of macromolecules. As such, oxidative stress leads to various protein, lipid and DNA modifications that can eventually lead to cell insult and increase of disease risk in humans. The main antioxidant in the organism is glutathione (GSH) that plays central role in defense against different cell insults. Thus, the cellular level of GSH concentration depends on the exposure to oxidative stress. The aim of this study was to evaluate oxidative status through evaluating GSH and malondialdehyde (MDA) level and baseline frequency of DNA damage in young female volunteers. Peripheral blood and urine samples intended for the study were taken from the volunteer blood donors, representing general population and were of the similar age and life-styles. All of them were healthy at the moment of blood and urine sampling and interviews. They were not occupationally exposed to genotoxic agents. None of them reported alcohol consumption, drugs intake, the presence of known inherited genetic disorders or chronic diseases. For the six month period prior to the blood sampling subjects had not been exposed to ionizing or non-ionizing radiation for diagnostic or therapeutic purposes. The concentration of GSH in blood as measure of body antioxidative status and level of MDA in the urine as indicator of oxidative damage to the lipids was measured. Additionally, to evaluate baseline frequency of DNA damage alkaline version of the comet assay was applied. Presented results will give an inside into oxidative status and its relation to DNA damage frequency of healthy female volunteers which can serve as baseline values for further biomonitoring assessment.

Curcumin is the major component of the spice turmeric Curcuma longa. It exhibits a diversity of b... more Curcumin is the major component of the spice turmeric Curcuma longa. It exhibits a diversity of beneficial effects, among them the antitumor activity. However, the complex network of cell response to this natural drug is not yet resolved. Specially the data are missing that could explain the mechanism involved in cell-resistance to curcumin. Using human laryngeal carcinoma HEp2 cells and their curcumin resistant 7T subline, we have investigated the cell response to this drug and molecular mechanisms involved in its resistance. Following the treatment with equimalar doses of curcumin 7T cells (as compared to HEp2 cells), exhibit reduced: accumulation of curcumin, induction of reactive oxidative species (ROS), lipid peroxidation, oxidative DNA damage, the fraction of cells in G2/M phase of the cell cycle, and the induction of apoptosis. The treatment with equitoxic doses of curcumin induced similar effects in both cell lines. However, the induction of ROS, oxidative DNA damage and the fraction of cell in G2/M phase are still lower in 7T cells. These results suggest that the cellular uptake of curcumin and defence of 7T subline against oxidative stress is involved in curcumin– resistance of 7T cells (but this resistance was not due to changes in glutathione or induction of superoxide dismutases (SOD1, SOD2) and catalase expression). These results suggest that curcumin is a molecule that induce a complex network of events involved in cell response, and that resistance to this natural compound is based on multiple factors.

International Journal of Molecular Sciences, Feb 17, 2023

Mutagenesis, Nov 1, 2022

One of the ways to impact emerging problems of unhealthy diet such as microbiota dysbiosis, infla... more One of the ways to impact emerging problems of unhealthy diet such as microbiota dysbiosis, inflammation, and oxidative stress is the application of probiotics and their incorporation into different food matrices. Discovery and selection of appropriate probiotic bacteria is challenging procedure especially for fermented meat products that have also been described as a potential source of resilient probiotic microorganisms. The aim of this study was to investigate probiotic bacteria Lactiplantibacillus plantarum 1K isolated from traditional fermented meat product for its potential beneficial properties. Furthermore, small probiotic metabolites were extracted, and their anti-inflammatory activity was tested in a lipopolysaccharide-stimulated inflammatory model on human peripheral blood mononuclear cells (PBMCs). Safety characteristics of metabolites including cytotoxicity and genotoxicity were also determined. Investigated probiotic strain exerted high antioxidant potential by viable cells but also by metabolite fraction. Viable cells retained the satisfactory antioxidant activity after gastrointestinal transit. Extracted probiotic metabolites significantly inhibited TNF-α production in LPS-stimulated PBMC thus exerting anti-inflammatory activity. Metabolites alone showed no cytotoxic or genotoxic activity toward isolated immune cells. Obtained results indicate the possibility to use fermented meat products as sources for specific probiotics that might provide antioxidant and anti-inflammatory benefits for the consumers.

Regulatory Toxicology and Pharmacology, Oct 1, 2020

Bee venom is used in traditional medicine to treat variety of diseases. In recent years it has al... more Bee venom is used in traditional medicine to treat variety of diseases. In recent years it has also been reported that the venom and, especially one of its major constituent’s melittin, possess anticancer properties. The aim of this chapter was to evaluate the cytotoxicity of whole bee venom, and melittin towards different types of tumor cells: human laryngeal HEp-2 and cervical carcinoma HeLa cells and their drug resistant sublines (CK2 and HeLa CK cells), breast adenocarcinoma MCF-7 cells, colon adenocarcinoma SW620 cells, and glioblastoma A1235 cells, as well as human embryonic kidney HEK-293 cells and normal Hef fibroblasts. Bee venom was tested in concentrations ranging from 0.4 μg/ml to 200 μg/ml, and melittin in concentrations from 0.1 μg/ml to 50 μg/ml. Cytotoxicity of whole bee venom, and melittin was evaluated using spectrophotometric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test. The morphology of treated cells was determined by light and fluorescent microscopy. Our results show that both, bee venom and melittin have strong cytotoxic potential towards different human cultured tumor cells, and that their effects are dose and cell type dependent. Melittin displayed even greater cytotoxicity to all types of cells tested. In addition, tumor cells were more sensitive to both, bee venom and melittin, as compared to the non-tumor cells. Depending on the origin, drug-resistant cells could be more sensitive to melittin (such as drug resistant cervical carcinoma cells) than parental cells. Both, bee venom and melittin altered morphological characteristics of treated cells. They were induced rapidly, in less than one hour following the treatment with bee venom or melittin. Light microscopy showed that bee venom and melittin treated cells exhibited significant morphological changes in addition to the cell viability reduction. Morphological features were rounded and granulated morphology, cell shrinkage and eventual detachment from the culture plates. Their fast staining with ethidium bromide suggests that both, bee venom and melittin given in higher doses induced probably necrotic type of cell death. Our further studies will focus on the mechanisms by which bee venom itself and its components lead to cell death. Our data in conjunction with other accumulating evidence on anti-proliferative and pro-death activity of bee venom and melittin indicate their possible use in the development of antitumor drugs.