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      Xylene Induces Oxidative Stress and Mitochondria Damage in Isolated Human Lymphocytes

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          Abstract

          Xylene is a cyclic hydrocarbon and an environmental pollutant. It is also used in medical technology, paints, dyes, polishes and in many industries as a solvent; therefore, an understanding of the interaction between xylene and human lymphocytes is of significant interest. Biochemical assessment was used to demonstrate that exposure of lymphocytes to xylene induces cytotoxicity (at 6 hr), generates intracellular reactive oxygen species, collapse of mitochondrial membrane potential, lysosomal injury, lipid peroxidation and depletion of glutathione (at 3 hr). The findings show that xylene triggers oxidative stress and organelle damage in lymphocytes. The results of our study suggest that the use of antioxidant, mitochondrial and lysosomal protective agents can be helpful for individuals subject to chronic exposure to xylene.

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          Lysosomes and oxidative stress in aging and apoptosis.

          The lysosomal compartment consists of numerous acidic vesicles (pH approximately 4-5) that constantly fuse and divide. It receives a large number of hydrolases from the trans-Golgi network, while their substrates arrive from both the cell's outside (heterophagy) and inside (autophagy). Many macromolecules under degradation inside lysosomes contain iron that, when released in labile form, makes lysosomes sensitive to oxidative stress. The magnitude of generated lysosomal destabilization determines if reparative autophagy, apoptosis, or necrosis will follow. Apart from being an essential turnover process, autophagy is also a mechanism for cells to repair inflicted damage, and to survive temporary starvation. The inevitable diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow oxidative formation of lipofuscin in long-lived postmitotic cells, where it finally occupies a substantial part of the volume of the lysosomal compartment. This seems to result in a misdirection of lysosomal enzymes away from autophagosomes, resulting in depressed autophagy and the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. This scenario might put aging into the category of autophagy disorders.
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            Induction of hsp70, hsp60, hsp83 and hsp26 and oxidative stress markers in benzene, toluene and xylene exposed Drosophila melanogaster: role of ROS generation.

            Exposure to benzene, toluene and xylene in the human population may pose a health risk. We tested a working hypothesis that these test chemicals cause cellular toxicity to a non-target organism, Drosophila melanogaster. Third instar larvae of D. melanogaster transgenic for hsp70, hsp83 and hsp26 and Oregon R(+) strain were exposed to 1.0-100.0 mM benzene, toluene and xylene for 2-48 h to examine the heat shock proteins (hsps), ROS generation, anti-oxidant stress markers and developmental end points. The test chemicals elicited a concentration- and time-dependent significant (p hsp83>or=hsp26 as evident by beta-galactosidase activity after 24 h. RT-PCR amplification studies in Oregon R(+) larvae revealed a similar induction pattern of these genes along with hsp60 in the order of hsp70>hsp60>hsp26>or=hsp83. Under similar experimental conditions, a significant induction of ROS generation and oxidative stress markers viz. superoxide dismutase, catalase, glutathione S-transferase, thioredoxin reductase, glutathione, malondialdehyde and protein carbonyl content was observed. Sub-organismal response was propagated towards organismal response i.e., a delay in the emergence of flies and their reproductive performance. While hsp70 was predominantly induced in the organism till 24 h of treatment with the test chemicals, a significant or insignificant regression of Hsp70 after 48 h was concurrent with a significant induction (p hsp83>or=hsp26 in comparison to the former. A significant positive correlation was observed between ROS generation and these hsps in the exposed organism till 24 h and a negative correlation between ROS generation and hsp70 in them after 48 h indicating a modulatory role of ROS in the induction of hsps. The study suggests that among the tested hsps, hsp70 may be used as an early bioindicator of cellular toxicity against benzene, toluene and xylene and D. melanogaster as an alternative animal model for screening the risk posed by environmental chemicals.
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              Influences of Environmental Chemicals on Atopic Dermatitis

              Atopic dermatitis is a chronic inflammatory skin condition including severe pruritus, xerosis, visible eczematous skin lesions that mainly begin early in life. Atopic dermatitis exerts a profound impact on the quality of life of patients and their families. The estimated lifetime prevalence of atopic dermatitis has increased 2~3 fold during over the past 30 years, especially in urban areas in industrialized countries, emphasizing the importance of life-style and environment in the pathogenesis of atopic diseases. While the interplay of individual genetic predisposition and environmental factors contribute to the development of atopic dermatitis, the recent increase in the prevalence of atopic dermatitis might be attributed to increased exposure to various environmental factors rather than alterations in human genome. In recent decades, there has been an increasing exposure to chemicals from a variety of sources. In this study, the effects of various environmental chemicals we face in everyday life - air pollutants, contact allergens and skin irritants, ingredients in cosmetics and personal care products, and food additives - on the prevalence and severity of atopic dermatitis are reviewed.
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                Author and article information

                Journal
                Toxicol Res
                Toxicol Res
                Toxicological Research
                Toxicological Research
                Korean Society of Toxicology
                1976-8257
                2234-2753
                July 2017
                15 July 2017
                : 33
                : 3
                : 233-238
                Affiliations
                [1 ]Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran
                [2 ]Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                Author notes
                Correspondence to: Jalal Pourahmad, Toxicology and Pharmacology Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, P. O. Box: 14155-6153, Tehran, Iran, E-mail: j.pourahmadjaktaji@ 123456utoronto.ca
                Article
                tr-33-233
                10.5487/TR.2017.33.3.233
                5523563
                28744355
                cdb43830-bf4c-4cc5-bcce-9af0e723faa1
                Copyright © 2017 The Korean Society Of Toxicology

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 April 2017
                : 20 May 2017
                : 31 May 2017
                Categories
                Original Article

                xylene,lymphocyte,cytotoxicity,mitochondrial damage,oxidative stress

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