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Assessments of Bioactive and Toxic Substances in Cellular and Animal...
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Assessments of Bioactive and Toxic Substances in Cellular and Animal Models

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (15 April 2025) | Viewed by 9723

Special Issue Editors

Dr. Anton Kovacik

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Guest Editor
Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
Interests: animal physiology; biochemistry; hematology; bioactive substances; trace elements; oxidative stress; ecotoxicology
Dr. Tomáš Jambor

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Guest Editor
Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
Interests: cell biology; reproductive toxicology; steroidogenesis; xenobiotics; natural compounds

Special Issue Information

Dear Colleagues,

Due to the increasing number of anthropogenic xenobiotics entering the environment, and considering the sophisticated systems developed by the body for the distribution, metabolism and elimination of xenobiotics that enter the body in various ways, the discipline of toxicology has been a very current and urgent issue in recent decades. As most of them can interact with cell surfaces or nuclear receptors, they can cause non-physiological alterations in cellular homeostasis even at low concentrations, which places them in a special category of toxic substances in terms of health risks. On the other hand, natural plant extracts have several biological effects (immunological, antimicrobial, anti-inflammatory and anti-cancer). In addition to their positive biological effects, the side effects that appear in conventional treatments are absent. The assessment of risk elements, xenobiotics, nanoparticles, and biologically active substances in animal cells and/or tissues, the study of ecotoxicological interactions and their effects on animal health indicators in natural and model conditions is currently a relevant topic.

Dr. Anton Kovacik
Dr. Tomáš Jambor
Guest Editors

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Keywords

  • cell biology
  • animal physiology
  • natural compounds
  • xenobiotics
  • trace elements
  • reproductive toxicology
  • oxidative status markers
  • health status
  • ecotoxicology

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Published Papers (7 papers)

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Research

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18 pages, 4375 KiB  
Article
Investigation of Cytotoxic, Antioxidant, Apoptotic/Necrotic Activity of Aquilaria agallocha Root Extract and Determination of Gene Expression Levels in HepG2, MCF-7 Cancer Cell Lines
by Semih Dalkılıç, Lütfiye Kadıoğlu Dalkılıç, Elgun İsbenov, Lütfü Uygur and Ceydanur Taşdemir
Life 2025, 15(4), 651; https://doi.org/10.3390/life15040651 - 16 Apr 2025
Viewed by 453
Abstract
Cancer is a common disease worldwide, and medicinal plants are widely used for its treatment. A. agallocha is a plant from the Thymelaeaceae family that is endemic to East Asia. Popularly known as the agar tree, this plant is used in the treatment [...] Read more.
Cancer is a common disease worldwide, and medicinal plants are widely used for its treatment. A. agallocha is a plant from the Thymelaeaceae family that is endemic to East Asia. Popularly known as the agar tree, this plant is used in the treatment of heart diseases, asthma, cough, ulcers, gout, inflammation, and pain. In this study, the cytotoxic, apoptotic/necrotic, and antioxidant activities of root extracts of A. agallocha and their effects on gene expression were investigated. Cytotoxic effects were analyzed by the MTT assay method, apoptotic/necrotic effects by the double staining method, and antioxidant effects by the DPPH radical scavenging assay. According to the results, the best cytotoxic effect in HepG2 cells was observed at 1000 µg/mL hexane extract. In MCF-7 cells, 250 µg/mL hexane extract showed the best activity. Antioxidant activity was highest in dH2O and lowest in the methanol extract. In gene expression analysis, hexane and methanol extracts decreased p53 expression in HepG2 cells, while acetone extract increased it. In addition, the expression of Bax and Bcl-2 genes generally increased. This study revealed the potent cytotoxic, antioxidant, and apoptotic effects of the A. agallocha extract. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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13 pages, 1584 KiB  
Article
Rapid and Accurate Genotoxicity Assessment Using the Neutral Comet Assay in Cyprinus carpio Cells
by Byeonghyeon So, Ji Ho Park, Minseon Kim, Hojun Lee, Jee Hee Yoon, Yoo Jin Lee, Duyeol Kim, Hyung Wook Kwon, Jihae Park, Taejun Han, Yun Haeng Lee and Joon Tae Park
Life 2025, 15(4), 603; https://doi.org/10.3390/life15040603 - 4 Apr 2025
Viewed by 389
Abstract
Genotoxins cause significant damage to the genetic material of aquatic organisms, requiring rapid and accurate assessment. Fish-derived cells sensitive to genotoxins have proven to be a useful tool for measuring genotoxicity, but the long treatment times required for measurement limit their application in [...] Read more.
Genotoxins cause significant damage to the genetic material of aquatic organisms, requiring rapid and accurate assessment. Fish-derived cells sensitive to genotoxins have proven to be a useful tool for measuring genotoxicity, but the long treatment times required for measurement limit their application in situations requiring rapid testing. Previous studies have shown that fish cells can be kept unstarved for up to 6 h using media containing 1% FBS. In this study, the 1% FBS/6 h parameter was used for genotoxicity assessment. Therefore, genotoxicity assessment was performed after only 6 h of genotoxin treatment in a medium containing 1% FBS. The new genotoxicity assessment method provided faster and more accurate genotoxicity data for climbazole and metolachlor than the existing assessment system using the 15% FBS/96 h parameter. Furthermore, these advantages of the new platform enabled the determination of the genotoxicity of various genotoxins, such as dibenz[a,h]anthracene and ethoprophos. In summary, we have developed a genotoxicity assessment that can generate genotoxicity data rapidly and accurately. This new platform will serve as a foundation for rapid genotoxicity assessment of many genotoxins. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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21 pages, 6332 KiB  
Article
Unveiling the Potential of Silymarin, Spirulina platensis, and Chlorella vulgaris towards Cardiotoxicity via Modulating Antioxidant Activity, Inflammation, and Apoptosis in Rats
by Hanem F. El-Gendy, Hanem K. Khalifa, Ahmed Omran, Reda M. S. Korany, Shaimaa Selim, Eman Hussein, Rashed A. Alhotan, Anam Ayyoub and Shimaa R. Masoud
Life 2024, 14(10), 1289; https://doi.org/10.3390/life14101289 - 11 Oct 2024
Cited by 3 | Viewed by 1789
Abstract
This study assessed the possible pharmacological effects of Chlorella vulgaris (Cg), Spirulina platensis (St), and silymarin (Sl) against thioacetamide (TA)-induced cardiotoxicity in rats, with a focus on their antioxidant, cardioprotective, and anti-inflammatory properties. The following is the random grouping of sixty male rats [...] Read more.
This study assessed the possible pharmacological effects of Chlorella vulgaris (Cg), Spirulina platensis (St), and silymarin (Sl) against thioacetamide (TA)-induced cardiotoxicity in rats, with a focus on their antioxidant, cardioprotective, and anti-inflammatory properties. The following is the random grouping of sixty male rats into six groups of ten animals each: the control (negative control), TA-intoxicated group (positive control; 300 mg/kg body weight (BW)), Sl + TA group (100 mg Sl/kg BW + TA), St + TA group (400 mg St/kg BW + TA), Cg + TA (400 mg Cg/kg BW + TA), and St + Cg + TA group (400 St + 400 Cg mg/kg BW + TA) were all administered for 30 days. At the start of the study, groups 2 through 6 were administered TA intraperitoneally at a dosage of 300 mg/kg BW for two consecutive days, with a 24 h gap between each dose, to induce cardiac damage. Blood samples were obtained to measure hematological parameters and perform biochemical assays, including lipid profiles and cardiac enzymes. For histopathology and immunohistochemistry determination, tissue samples were acquired. The current findings showed that TA injection caused hematological alterations and cardiac injury, as evidenced by greater serum levels of troponin I, creatine kinase-MB, and total creatine kinase (p < 0.05), as well as significantly elevated serum malondialdehyde and decreased serum total antioxidant capacity (p < 0.05) concentrations. Moreover, an increase in blood low-density lipoprotein and total cholesterol concentration (p < 0.05) was recorded in the TA group. There were alterations in the heart tissue’s histological structure of the TA group compared to the control ones. These alterations were characterized by vacuolar degeneration of myocytes, loss of cross striation, coagulative necrosis, and fibrosis of interstitial tissue, which was ameliorated by the supplementation of SI, St, and Cg. The TA-intoxicated group showed weak expression of B-cell lymphoma protein 2 (p < 0.05) and strong immunoreactivity of tumor necrosis factor-α and B-cell lymphoma protein 2-associated X (p < 0.05). However, the groups receiving Sl, St, and Cg experienced the opposite. The administration of Sl, St, Cg, and St + Cg along with TA significantly improved and restored (p < 0.05) erythrogram indices, including RBCs, hemoglobin, total leukocytic count, lymphocytes, and monocyte, to the normal control values. The administration of Sl, St, and Cg alleviated the cardiotoxicity caused by TA via reducing oxidative stress, inflammatory markers, and apoptosis in heart tissue. In summary, the current findings suggest that the treatment with Sl, St, and Cg was beneficial in ameliorating and reducing the cardiotoxicity induced by TA in rats. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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18 pages, 5936 KiB  
Article
Morphophysiological and Histopathological Effects of Ammonium Sulfate Fertilizer on Aporrectodea trapezoides (Dugès, 1828) Earthworm
by Khaoula Aouaichia, Nedjoud Grara, Kamel Eddine Bazri, Edison Barbieri, Nedjma Mamine, Hadia Hemmami, Anna Capaldo, Luigi Rosati and Stefano Bellucci
Life 2024, 14(9), 1209; https://doi.org/10.3390/life14091209 - 23 Sep 2024
Cited by 1 | Viewed by 1448
Abstract
The present study used the adult earthworm Aporrectodea trapezoides as a bioindicator species to look into the possible dangers of ammonium sulfate (AS) fertilizer. Two complementary toxicity tests were conducted to determine the LC50values, growth rate inhibition, morphological alterations, and histopathological texture of [...] Read more.
The present study used the adult earthworm Aporrectodea trapezoides as a bioindicator species to look into the possible dangers of ammonium sulfate (AS) fertilizer. Two complementary toxicity tests were conducted to determine the LC50values, growth rate inhibition, morphological alterations, and histopathological texture of worms. The lethality test included four increasing concentrations of AS fertilizer (ranging from 2500 to 7500 mg/kg of dry soil weight (d.w.)), while sub-lethal concentrations were based on 10%, 30%, 40%, and 50% of the 14-day median lethal concentration (LC50), with a control group included for both tests. The LC(50) values for AS fertilizer were significantly higher at 7 days (4831.13 mg/kg d.w.) than at 14 days (2698.67 mg/kg d.w.) of exposure. Notably, earthworms exhibited significant growth rate inhibition under exposure to various concentrations and time durations (14/28 exposure days). Morphological alterations such as clitellar swelling, bloody lesions, whole body coiling and constriction, body strangulation, and fragmentation were accentuated steadily, with higher concentrations. Histopathological manifestations included severe injuries to the circular and longitudinal muscular layers, vacuolation, muscle layer atrophy, degradation of the chloragogenous tissue in the intestine, collapsed digestive epithelium of the pharynx with weak reserve inclusion, and fibrosis of blood vessels. These effects were primarily influenced by increasing concentrations of fertilizer and time exposure. The study highlights the strong relationship between concentration and exposure time responses and underscores the potential of A. trapezoides earthworms as valuable biological control agents against acidic ammonium sulfate fertilizer. Importantly, this research contributes to the use of such biomarkers in evaluating soil toxicity and the biological control of environmental risk assessment associated with chemical fertilizers. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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17 pages, 336 KiB  
Article
In Vitro Evaluation of Synergistic Essential Oils Combination for Enhanced Antifungal Activity against Candida spp.
by Lukáš Hleba, Miroslava Hlebová and Ivana Charousová
Life 2024, 14(6), 693; https://doi.org/10.3390/life14060693 - 28 May 2024
Cited by 3 | Viewed by 2404
Abstract
In recent years, a significant number of infections have been attributed to non-albicidal Candida species (NAC), mainly due to the increasing resistance of NAC to antifungal agents. As only a few antifungal agents are available (azoles, echinocandins, polyenes, allylamines and nucleoside analogues), it [...] Read more.
In recent years, a significant number of infections have been attributed to non-albicidal Candida species (NAC), mainly due to the increasing resistance of NAC to antifungal agents. As only a few antifungal agents are available (azoles, echinocandins, polyenes, allylamines and nucleoside analogues), it is very important to look for possible alternatives to inhibit resistant fungi. One possibility could be essential oils (EOs), which have been shown to have significant antifungal and antibacterial activity. Therefore, in this study, the efficacy of 12 EOs and their combinations was evaluated against four yeasts of the genus Candida (C. albicas, C. glabrata, C. tropicalis and C. parapsilosis). GC-MS and GC-MS FID techniques were used for the chemical analysis of all EOs. VITEK-2XL was used to determine the antifungal susceptibility of the tested Candida spp. strains. The agar disc diffusion method was used for primary screening of the efficacy of the tested EOs. The broth dilution method was used to determine the minimum inhibitory concentrations (MICs) of the most potent EOs. After MIC cultivation, the minimum fungicidal concentration (MFC) was determined on Petri dishes (60 mm). The synergistic effect of combined EOs was evaluated using the checkerboard method and expressed as a fractional inhibitory concentration index (FICI). The results showed that ginger > ho-sho > absinth > dill > fennel > star anise > and cardamom were the most effective EOs. For all Candida species tested, the synergy was mainly observed in these combinations: ginger/fennel for C. albicans FICI 0.25 and C. glabrata, C. tropicalis and C. parapsilosis FICI 0.5 and absinth/fennel for C. albicans FICI 0.3125, C. tropicalis FICI 0.3125 and C. parapsilosis FICI 0.375. Our results suggest that the resistance of fungal pathogens to available antifungals could be reduced by combining appropriate EOs. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
15 pages, 6132 KiB  
Article
The Influence of Phenol on the Growth, Morphology and Cell Division of Euglena gracilis
by Alexandra Lukáčová, Diana Lihanová, Terézia Beck, Roman Alberty, Dominika Vešelényiová, Juraj Krajčovič and Matej Vesteg
Life 2023, 13(8), 1734; https://doi.org/10.3390/life13081734 - 12 Aug 2023
Cited by 1 | Viewed by 2106
Abstract
Phenol, a monocyclic aromatic hydrocarbon with various commercial uses, is a major pollutant in industrial wastewater. Euglena gracilis is a unicellular freshwater flagellate possessing secondary chloroplasts of green algal origin. This protist has been widely used for monitoring the biological effect of various [...] Read more.
Phenol, a monocyclic aromatic hydrocarbon with various commercial uses, is a major pollutant in industrial wastewater. Euglena gracilis is a unicellular freshwater flagellate possessing secondary chloroplasts of green algal origin. This protist has been widely used for monitoring the biological effect of various inorganic and organic environmental pollutants, including aromatic hydrocarbons. In this study, we evaluate the influence of different phenol concentrations (3.39 mM, 3.81 mM, 4.23 mM, 4.65 mM, 5.07 mM, 5.49 mM and 5.91 mM) on the growth, morphology and cell division of E. gracilis. The cell count continually decreases (p < 0.05–0.001) over time with increasing phenol concentration. While phenol treatment does not induce bleaching (permanent loss of photosynthesis), the morphological changes caused by phenol include the formation of spherical (p < 0.01–0.001), hypertrophied (p < 0.05) and monster cells (p < 0.01) and lipofuscin bodies. Phenol also induces an atypical form of cell division of E. gracilis, simultaneously producing more than 2 (3–12) viable cells from a single cell. Such atypically dividing cells have a symmetric “star”-like shape. The percentage of atypically dividing cells increases (p < 0.05) with increasing phenol concentration. Our findings suggest that E. gracilis can be used as bioindicator of phenol contamination in freshwater habitats and wastewater. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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Review

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20 pages, 810 KiB  
Review
Can Bisphenols Alter the Inflammation Process?
by Denis Bazany, Hana Greifova, Lucia Zuscikova, Katarina Tokarova, Tomas Jambor, Anton Kovacik and Norbert Lukac
Life 2025, 15(5), 782; https://doi.org/10.3390/life15050782 - 14 May 2025
Viewed by 191
Abstract
This review’s main purpose is to draw attention to the possible influence of widely used bisphenols on the inflammatory process. Bisphenols are endocrine-disrupting chemicals that are produced worldwide in great quantities. From this point of view, it is very important to clarify their [...] Read more.
This review’s main purpose is to draw attention to the possible influence of widely used bisphenols on the inflammatory process. Bisphenols are endocrine-disrupting chemicals that are produced worldwide in great quantities. From this point of view, it is very important to clarify their influence on innate immune reactions, which protect the integrity of the body against the action of various pathogens on a daily basis. The inflammation process consists of several key factors that are produced at different levels of this reaction. Each of these levels can be affected by endocrine disruptors, from the point of view of modifying either the immune system cells that intervene in this process or the way in which they produce inflammatory mediators. The development of new recommendations for the use of bisphenols is a complex issue given their influence on inflammatory processes. Because the immune system and immune response are so intricate, bisphenols may pose more risk to humans than is presently recognized. This paper discusses the classification of bisphenols, the fundamental mechanism of inflammation, the characterization of inflammatory mediators, and the current knowledge of the molecular mechanisms behind the impact of bisphenols on the inflammatory response. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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