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
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.
Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac ...dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg−1). Two days later, CA (50 mg kg−1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.
The comet assay is a well-accepted biomonitoring tool to examine the effect of dietary, lifestyle, environmental and occupational exposure on levels of DNA damage in human cells. With such a wide ...range of determinants for DNA damage levels, it becomes challenging to deal with confounding and certain factors are inter-related (e.g. poor nutritional intake may correlate with smoking status). This review describes the effect of intrinsic (i.e. sex, age, tobacco smoking, occupational exposure and obesity) and extrinsic (season, environmental exposures, diet, physical activity and alcohol consumption) factors on the level of DNA damage measured by the standard or enzyme-modified comet assay. Although each factor influences at least one comet assay endpoint, the collective evidence does not indicate single factors have a large impact. Thus, controlling for confounding may be necessary in a biomonitoring study, but none of the factors is strong enough to be regarded a priori as a confounder. Controlling for confounding in the comet assay requires a case-by-case approach. Inter-laboratory variation in levels of DNA damage and to some extent also reproducibility in biomonitoring studies are issues that have haunted the users of the comet assay for years. Procedures to collect specimens, and their storage, are not standardized. Likewise, statistical issues related to both sample-size calculation (before sampling of specimens) and statistical analysis of the results vary between studies. This review gives guidance to statistical analysis of the typically complex exposure, co-variate, and effect relationships in human biomonitoring studies.
Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and
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 A
(PLA
), 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.
The aim of this study was to test the phytotoxicity and mode of action of bisphenol A (BPA) on
using a multibiomarker approach.
roots were exposed to BPA in concentration range 0-50 mg L
for 3 days. ...BPA even in the lowest applied concentration (1 mg L
) reduced root length, root fresh weight, and mitotic index. Additionally, the lowest BPA concentration (1 mg L
) decreased the level of gibberellic acid (GA
) in root cells. BPA at concentration 5 mg L
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
) induced genome damage detected as an increase in micronucleus (MNs) and nuclear buds (NBUDs). BPA at >25 mg L
induced synthesis of phytochemicals. Results of this study using multibiomarker approach indicate that BPA is phytotoxic to
roots and has shown genotoxic potential to plants, thus its presence in the environment should be monitored.
DNA damage is known to be associated with many adverse health outcomes, including cancer and chronic diseases, but also with the process of aging. Empirical evidence has shown that environmental ...exposures, such as certain lifestyle factors, can affect a variety of health-related biomarkers and also impact the stability of DNA through the upregulation of the antioxidant defense system and alteration of its repair capacity. In addition to exercising, diet is an important lifestyle factor that can affect the development of a variety of chronic diseases and growing evidence suggests that plant-based diets, including vegetarianism, may promote health, longevity, and well-being. Therefore, we aimed to assess the primary DNA damage in 32 young healthy females from Zagreb, Croatia, based on their dietary preferences. The participants were divided into two groups: vegetarians and non-vegetarians, where the non-vegetarian group was further divided into omnivores (traditional mixed diet) and pescatarians (consumption of fish and seafood). According to statistical analysis, the DNA damage measured in whole blood cells expressed as the % tail DNA was significantly (
< 0.05) higher in vegetarians (3.6 ± 1.1%) compared to non-vegetarians (2.8 ± 1.0%). When further dividing the participants into specific sub-groups, lower DNA damage was observed amongst omnivorous subjects (3.2 ± 0.8%) compared to vegetarians, with the lowest DNA damage found in females practicing a pescatarian diet (2.4 ± 1.1%). Although a vegetarian diet can lead to a higher intake of specific vitamins and micronutrients, it can also lead to a deficiency of iron, calcium, and total proteins, which may affect genome stability and induce oxidative stress. Even though our results have shown that the pescatarian diet would be more beneficial in terms of maintaining DNA integrity, further research should be carried out to assess how specific dietary preferences affect DNA integrity on a larger scale.
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 (
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.
Non-communicable diseases (NCD) and lifestyle, particularly diet, have a close relationship. Based on the recent statistics, Croatian men and women lead in European overweight lists, which implies ...pessimistic prognosis in terms of incidence and prevalence of NCDs in the future. One of the possible solutions to overcome weight problems is turn to traditional balanced and sustainable diets, such as the Mediterranean diet. In this study, we assessed adherence towards Mediterranean diet using a validated questionnaire in an online survey and associated adherence scores with several demographic and anthropometric data. Based on the results of a validated Mediterranean Diet Adherence Screener (N = 3326), we assessed the adherence score to be 7.6 ± 2.5. The score tended to depend on sex, residence, age, education, income, and body mass index (BMI); indeed, women, residents of a coastal part of the country, older volunteers, those possessing a higher education degree, those with higher income, and those with lower BMI were associated with higher scores. As income was one of the significant findings related to higher adherence scores, we developed a dietary plan complying with Mediterranean diet principles that, on average, costed less than the average traditional balanced diet menu. Taken together, this study brought new findings regarding target groups who need to be encouraged to make lifestyle changes, and highlighted the first steps on how to make them.
Residues of anti-neoplastic drugs represent new and emerging pollutants in aquatic environments. Many of these drugs are genotoxic, and it has been postulated that they can cause adverse effects in ...aquatic ecosystems. 5-Fluorouracil (5-FU) is one of the most extensively used anti-neoplastic drugs in cancer therapy, and this article describes the results of the first investigation using a two-generation toxicity study design with zebrafish (Danio rerio). Exposure of zebrafish to 5-FU (0.01, 1.0 and 100 μg/L) was initiated with adult zebrafish (F0 generation) and continued through the hatchings and adults of the F1 generation, and the hatchings of the F2 generation, to day 33 post-fertilisation. The exposure did not affect survival, growth and reproduction of the zebrafish; however, histopathological changes were observed in the liver and kidney, along with genotoxic effects, at all 5-FU concentrations. Increases in DNA damage determined using the comet assay were significant in the liver and blood cells, but not in the gills and gonads. In erythrocytes, a significant, dose-dependent increase in frequency of micronuclei was observed at all 5-FU concentrations. Whole genome transcriptomic analysis of liver samples of F1 generation zebrafish exposed to 0.01 μg/L and 1 μg/L 5-FU revealed dose-dependent increases in the number of differentially expressed genes, including up-regulation of several DNA-damage-responsive genes and oncogenes (i.e., jun, myca). Although this chronic exposure to environmentally relevant concentrations of 5-FU did not affect the reproduction of the exposed zebrafish, it cannot be excluded that 5-FU can lead to degenerative changes, including cancers, which over long-term exposure of several generations might affect fish populations. The data from this study contribute to a better understanding of the potential consequences of chronic exposure of fish to low concentrations of anti-neoplastic drugs, and they demonstrate that further studies into multi-generation toxicity are needed.
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•Residues of anti-neoplastic drugs are emerging pollutants in aquatic environments.•Missing chronic ecotoxicity data constitute a critical knowledge gap.•Zebrafish two-generation chronic toxicity study of 5-FU was performed.•Genotoxic effects were detected at environmental concentrations.•Gene expression analysis revealed up-regulation of oncogenes.
The study aimed to investigate toxicity and the mechanism of toxicity of two
mycotoxins, deoxynivalenol (DON) and zearalenone (ZEA). DON and ZEA were applied to HepG2 cells as single compounds and in ...combination at low environmentally relevant concentrations. HepG2 cells were exposed to DON (0.5, 1, and 2 µM), ZEA (5, 10, and 20 µM) or their combinations (1 µM DON + 5 µM ZEA, 1 µM DON + 10 µM ZEA and 1 µM DON + 20 µM ZEA) for 24 h and cell viability, DNA damage, cell cycle and proliferation were assessed. Both mycotoxins reduced cell viability, however, combined treatment with DON and ZEA resulted in higher reduction of cell viability. DON (1 µM) induced primary DNA damage, while DON (1 µM) in combination with higher ZEA concentrations showed antagonistic effects compared to DON alone at 1 µM. DON arrested HepG2 cells in G2 phase and significantly inhibited cell proliferation, while ZEA had no significant effect on cell cycle. The combined treatment with DON and ZEA arrested cells in G2 phase to a higher extend compared to treatment with single mycotoxins. Potentiating effect observed after DON and ZEA co-exposure at environmentally relevant concentrations indicates that in risk assessment and setting governments' regulations, mixtures of mycotoxins should be considered.
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