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Special Issue "Molecular Mechanisms of Toxic and Activated Effects of Exogenous Compounds"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 15 January 2024 | Viewed by 6562

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Prof. Dr. Nadezhda S. Kudryasheva

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Institute of Biophysics, Federal Research Center, Siberian Branch of Russian Academy of Sciences, 660041 Krasnoyarsk, Russia
Interests: physicochemistry of biological objects; molecular spectroscopy; structure of molecules; chemiluminescence; bioluminescence; low-dose effects; hormesis; toxicity; radiotoxicity; antioxidant activity; bioactive compounds
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Dear Colleagues,

All living organisms are constantly exposed to exogenous compounds, which might disturb the natural metabolic equilibrium. Responses of organisms to these exposures are complex, being functions from organismal peculiarities and characteristics of the exogenous compounds, namely, physicochemical parameters and concentrations. Low-concentration exposures can initiate a ‘compensative’ response that is considered a result of the organism streaming to the equilibrium, with possible ‘overcompensation’ and activation of organismal physiological functions. The activation is usually discussed in terms of the ‘hormesis’ phenomenon. Higher concentrations of exogenous compounds and/or their chemical reactivity result in inhibition of physiological functions, i.e., they initiate a ‘toxic’ effect. Knowledge on the molecular mechanisms of both toxic and activated effects of exogenous compounds is highly important as it (1) provides information on the prediction of the bioeffects of exogenous compounds, (2) helps in overcoming negative consequences, and (3) allows the application of positive results.

We welcome studies of the bioeffects of different compounds with special attention paid to physicochemical processes and molecular conversions in biochemical and cellular systems.

Prof. Dr. Nadezhda S. Kudryasheva
Guest Editor

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Keywords

exogenous compounds
bioeffects
toxicity
low-concentration exposures
high concentrations exposures
low-dose effects
activated effects

Published Papers (5 papers)

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Research

Open AccessCommunication

Kinetic Intricacies of the Light Emission and Antiradical Influence of Exogenous Bioantioxidants Transformation Products in the Chemiluminescence Bioantioxidant Assay

and

Rostislav F. Vasil’ev

Int. J. Mol. Sci. 2023, 24(10), 8486; https://doi.org/10.3390/ijms24108486 - 09 May 2023

Viewed by 552

Abstract

The subject matter of the reported work refers to studying the interactions followed by the excited-state generation, which are chemical models of oxidative processes leading to a weak light emission emerging from living cells, and to explore the possibilities of using them as tools for evaluating the activity of oxygen-metabolism modulators, most prominently, natural bioantioxidants of biomedical value in particular. Methodologically, major attention is paid to analyzing the shapes of the time profiles of the light emission derived from a model sensory system in the presence of lipid samples of vegetable and animal (fish) origin rich in bioantioxidants. As a result, a modified reaction mechanism involving 12 elementary steps is proposed to rationalize the light-emission kinetics in the presence of natural bioantioxidants. We conclude that free radicals formed from bioantioxidants and their dimerization products contribute significantly to the general antiradical activity of lipid samples, which should be taken into account in developing efficient bioantioxidant assays for biomedical applications and while establishing the mechanisms of bioantioxidant effects on metabolic processes in vivo. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Toxic and Activated Effects of Exogenous Compounds)

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Open AccessArticle

Enzyme Inhibition-Based Assay to Estimate the Contribution of Formulants to the Effect of Commercial Pesticide Formulations

Elena N. Esimbekova

Valeriya P. Kalyabina

Kseniya V. Kopylova

Victoria I. Lonshakova-Mukina

and

Valentina A. Kratasyuk

Int. J. Mol. Sci. 2023, 24(3), 2268; https://doi.org/10.3390/ijms24032268 - 23 Jan 2023

Cited by 2 | Viewed by 1284

Abstract

Pesticides can affect the health of individual organisms and the function of the entire ecosystem. Therefore, thorough assessment of the risks associated with the use of pesticides is a high-priority task. An enzyme inhibition-based assay is used in this study as a convenient and quick tool to study the effects of pesticides at the molecular level. The contribution of formulants to toxicological properties of the pesticide formulations has been studied by analyzing effects of 7 active ingredients of pesticides (AIas) and 10 commercial formulations based on them (AIfs) on the function of a wide range of enzyme assay systems differing in complexity (single-, coupled, and three-enzyme assay systems). Results have been compared with the effects of AIas and AIfs on bioluminescence of the luminous bacterium Photobacterium phosphoreum. Mostly, AIfs produce a considerably stronger inhibitory effect on the activity of enzyme assay systems and bioluminescence of the luminous bacterium than AIas, which confirms the contribution of formulants to toxicological properties of the pesticide formulation. Results of the current study demonstrate that “inert” ingredients are not ecotoxicologically safe and can considerably augment the inhibitory effect of pesticide formulations; therefore, their use should be controlled more strictly. Circular dichroism and fluorescence spectra of the enzymes used for assays do not show any changes in the protein structure in the presence of commercial pesticide formulations during the assay procedure. This finding suggests that pesticides produce the inhibitory effect on enzymes through other mechanisms. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Toxic and Activated Effects of Exogenous Compounds)

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Open AccessCommunication

Toxicity of Different Types of Surfactants via Cellular and Enzymatic Assay Systems

Oleg S. Sutormin

Elizaveta M. Kolosova

Irina G. Torgashina

Valentina A. Kratasyuk

Nadezhda S. Kudryasheva

Julia S. Kinstler

and

Devard I. Stom

Int. J. Mol. Sci. 2023, 24(1), 515; https://doi.org/10.3390/ijms24010515 - 28 Dec 2022

Viewed by 1490

Abstract

Surfactants have a widespread occurrence, not only as household detergents, but also in their application in industry and medicine. There are numerous bioassays for assessing surfactant toxicity, but investigations of their impact on biological systems at the molecular level are still needed. In this paper, luminous marine bacteria and their coupled NAD(P)H:FMN-oxidoreductase + luciferase (Red + Luc) enzyme system was applied to examine the effects of different types of surfactants, including cationic cetyltrimethylammonium bromide (CTAB), non-ionic polyoxyethylene 20 sorbitan monooleate (Tween 80) and anionic sodium lauryl sulfate (SLS), and to assess whether the Red + Luc enzyme system can be used as a more sensitive indicator of toxicity. It was shown that the greatest inhibitory effect of the surfactants on the activity of luminous bacteria and the Red + Luc enzyme system was in the presence of SLS samples. The calculated IC₅₀ and EC₅₀ values of SLS were 10⁻⁵ M and 10⁻² M for the enzymatic and cellular assay systems, respectively. The results highlight the benefits of using the enzymatic assay system in ecotoxicology as a tool for revealing surfactant effects on intracellular proteins if the cellular membrane is damaged under a long-term exposure period in the presence of the surfactants. For this purpose, the bioluminescent enzyme-inhibition-based assay could be used as an advanced research tool for the evaluation of surfactant toxicity at the molecular level of living organisms due to its technical simplicity and rapid response time. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Toxic and Activated Effects of Exogenous Compounds)

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Open AccessArticle

Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins

and

Int. J. Mol. Sci. 2022, 23(19), 11032; https://doi.org/10.3390/ijms231911032 - 20 Sep 2022

Viewed by 1173

Abstract

Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by reactive oxygen species (ROS) production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. HOCbl increased the rate of oxidation of thiols to a greater extent than CNCbl, but quenched ROS in combination with certain thiols. Oxidation catalyzed by CNCbl was generally slower. Yet, the absence of ROS quenching resulted in their higher accumulation. The aforementioned results might explain a more pronounced cytotoxicity induced by combinations of thiols with CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved. Our results might also be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Toxic and Activated Effects of Exogenous Compounds)

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Open AccessArticle

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Prevents Asbestos-Induced Inflammation and Genotoxic Cell Damage in Human Mesothelial Cells

and

Melpo Christofidou-Solomidou

Int. J. Mol. Sci. 2022, 23(17), 10085; https://doi.org/10.3390/ijms231710085 - 03 Sep 2022

Cited by 2 | Viewed by 1313

Abstract

Although alveolar macrophages play a critical role in malignant transformation of mesothelial cells following asbestos exposure, inflammatory and oxidative processes continue to occur in the mesothelial cells lining the pleura that may contribute to the carcinogenic process. Malignant transformation of mesothelial cells following asbestos exposure occurs over several decades; however, amelioration of DNA damage, inflammation, and cell injury may impede the carcinogenic process. We have shown in an in vitro model of asbestos-induced macrophage activation that synthetic secoisolariciresinol diglucoside (LGM2605), given preventively, reduced inflammatory cascades and oxidative/nitrosative cell damage. Therefore, it was hypothesized that LGM2605 could also be effective in reducing asbestos-induced activation and the damage of pleural mesothelial cells. LGM2605 treatment (50 µM) of huma n pleural mesothelial cells was initiated 4 h prior to exposure to asbestos (crocidolite, 20 µg/cm²). Supernatant and cells were evaluated at 0, 2, 4, and 8 h post asbestos exposure for reactive oxygen species (ROS) generation, DNA damage (oxidized guanine), inflammasome activation (caspase-1 activity) and associated pro-inflammatory cytokine release (IL-1β, IL-18, IL-6, TNFα, and HMGB1), and markers of oxidative stress (malondialdehyde (MDA) and 8-iso-prostaglandin F2a (8-iso-PGF2α). Asbestos induced a time-dependent ROS increase that was significantly (p < 0.0001) reduced (29.4%) by LGM2605 treatment. LGM2605 pretreatment also reduced levels of asbestos-induced DNA damage by 73.6% ± 1.0%. Although levels of inflammasome-activated cytokines, IL-1β and IL-18, reached 29.2 pg/mL ± 0.7 pg/mL and 43.9 pg/mL ± 0.8 pg/mL, respectively, LGM2605 treatment significantly (p < 0.0001) reduced cytokine levels comparable to baseline (non-asbestos exposed) values (3.8 pg/mL ± 0.2 pg/mL and 5.4 pg/mL ± 0.2 pg/mL, respectively). Furthermore, levels of IL-6 and TNFα in asbestos-exposed mesothelial cells were high (289.1 pg/mL ± 2.9 pg/mL and 511.3 pg/mL ± 10.2 pg/mL, respectively), while remaining undetectable with LGM2605 pretreatment. HMGB1 (a key inflammatory mediator and initiator of malignant transformation) release was reduced 75.3% ± 0.4% by LGM2605. Levels of MDA and 8-iso-PGF2α, markers of oxidative cell injury, were significantly (p < 0.001) reduced by 80.5% ± 0.1% and 76.6% ± 0.3%, respectively. LGM2605, given preventively, reduced ROS generation, DNA damage, and inflammasome-activated cytokine release and key inflammatory mediators implicated in asbestos-induced malignant transformation of normal mesothelial cells. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Toxic and Activated Effects of Exogenous Compounds)

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