Impact of Aging and Ergothioneine Pre-treatment on Naphthalene Toxicity in Lung

Overview

Journal Toxicol Lett

Publisher Elsevier

Specialty Toxicology

Date 2024 May 20

PMID 38768835

Authors

Veneese Jb Evans

Xiangmeng Wu

Kyle K Tran

Shanlea K Tabofunda

Liang Ding

Lei Yin

Patricia Edwards

Qing-Yu Zhang

Xinxin Ding

Laura S Van Winkle

Affiliations

Soon will be listed here.

Abstract

Aging increases susceptibility to lung disease, but the topic is understudied, especially in relation to environmental exposures with the bulk of rodent studies using young adults. This study aims to define the pulmonary toxicity of naphthalene (NA) and the impacts of a dietary antioxidant, ergothioneine (ET), in the liver and lungs of middle-aged mice. NA causes a well-characterized pattern of conducting airway epithelial injury in the lung in young adult mice, but NA's toxicity has not been characterized in middle-aged mice, aged 1-1.5 years. ET is a dietary antioxidant that is synthesized by bacteria and fungi. The ET transporter (ETT), SLC22A4, is upregulated in tissues that experience high levels of oxidative stress. In this study, middle-aged male and female C57BL/6 J mice, maintained on an ET-free synthetic diet from conception, were gavaged with 70 mg/kg of ET for five consecutive days. On day 8, the mice were exposed to a single intraperitoneal NA dose of 50, 100, 150, or 200 mg/kg. At 24 hours post NA injection samples were collected and analyzed for ET concentration and reduced (GSH) and oxidized glutathione (GSSG) concentrations. Histopathology, morphometry, and gene expression were examined. Histopathology of mice exposed to 100 mg/kg of NA suggests reduction in toxicity in the terminal airways of both male (p ≤ 0.001) and female (p ≤ 0.05) middle-aged mice by the ET pretreatment. Our findings in this study are the first to document the toxicity of NA in middle-aged mice and show some efficacy of ET in reducing NA toxicity.

References

Arduini A, Eddy L, Hochstein P . The reduction of ferryl myoglobin by ergothioneine: a novel function for ergothioneine. Arch Biochem Biophys. 1990; 281(1):41-3. DOI: 10.1016/0003-9861(90)90410-z. View

Liu H, Tang W, Wang X, Jiang J, Zhang W, Wang W . Safe and Effective Antioxidant: The Biological Mechanism and Potential Pathways of Ergothioneine in the Skin. Molecules. 2023; 28(4). PMC: 9967237. DOI: 10.3390/molecules28041648. View

Zhu Y, Carvey P, Ling Z . Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res. 2006; 1090(1):35-44. PMC: 1868496. DOI: 10.1016/j.brainres.2006.03.063. View

Salama S, Omar H . Modulating NF-κB, MAPK, and PI3K/AKT signaling by ergothioneine attenuates iron overload-induced hepatocellular injury in rats. J Biochem Mol Toxicol. 2021; 35(5):e22729. DOI: 10.1002/jbt.22729. View

Hsia C, Hyde D, Ochs M, Weibel E . An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010; 181(4):394-418. PMC: 5455840. DOI: 10.1164/rccm.200809-1522ST. View

Wang H, Liu H, Liu R . Gender difference in glutathione metabolism during aging in mice. Exp Gerontol. 2003; 38(5):507-17. DOI: 10.1016/s0531-5565(03)00036-6. View

Orellana C, Marcellin E, Gray P, Nielsen L . Overexpression of the regulatory subunit of glutamate-cysteine ligase enhances monoclonal antibody production in CHO cells. Biotechnol Bioeng. 2017; 114(8):1825-1836. DOI: 10.1002/bit.26316. View

Plopper C, Chang A, Pang A, Buckpitt A . Use of microdissected airways to define metabolism and cytotoxicity in murine bronchiolar epithelium. Exp Lung Res. 1991; 17(2):197-212. DOI: 10.3109/01902149109064411. View

Abdo K, Grumbein S, Chou B, Herbert R . Toxicity and carcinogenicity study in F344 rats following 2 years of whole-body exposure to naphthalene vapors. Inhal Toxicol. 2001; 13(10):931-50. DOI: 10.1080/089583701752378179. View

10.

Fanucchi M, Buckpitt A, Murphy M, Plopper C . Naphthalene cytotoxicity of differentiating Clara cells in neonatal mice. Toxicol Appl Pharmacol. 1997; 144(1):96-104. DOI: 10.1006/taap.1997.8119. View

11.

Forman H, Zhang H . Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021; 20(9):689-709. PMC: 8243062. DOI: 10.1038/s41573-021-00233-1. View

12.

Lange N, Sparrow D, Vokonas P, Litonjua A . Vitamin D deficiency, smoking, and lung function in the Normative Aging Study. Am J Respir Crit Care Med. 2012; 186(7):616-21. PMC: 3480523. DOI: 10.1164/rccm.201110-1868OC. View

13.

Carratt S, Kovalchuk N, Ding X, Van Winkle L . Metabolism and Lung Toxicity of Inhaled Naphthalene: Effects of Postnatal Age and Sex. Toxicol Sci. 2019; 170(2):536-548. PMC: 6657577. DOI: 10.1093/toxsci/kfz100. View

14.

Royce F, Van Winkle L, Yin J, Plopper C . Comparison of regional variability in lung-specific gene expression using a novel method for RNA isolation from lung subcompartments of rats and mice. Am J Pathol. 1996; 148(6):1779-86. PMC: 1861634. View

15.

Phimister A, Nagasawa H, Buckpitt A, Plopper C . Prevention of naphthalene-induced pulmonary toxicity by glutathione prodrugs: roles for glutathione depletion in adduct formation and cell injury. J Biochem Mol Toxicol. 2005; 19(1):42-51. DOI: 10.1002/jbt.20052. View

16.

Cheah I, Halliwell B . Could Ergothioneine Aid in the Treatment of Coronavirus Patients?. Antioxidants (Basel). 2020; 9(7). PMC: 7402156. DOI: 10.3390/antiox9070595. View

17.

Stelck R, Baker G, Sutherland K, Van Winkle L . Estrous cycle alters naphthalene metabolism in female mouse airways. Drug Metab Dispos. 2005; 33(11):1597-602. DOI: 10.1124/dmd.105.005124. View

18.

Kc R, Shukla S, Gautam S, Hansbro P, OToole R . The role of environmental exposure to non-cigarette smoke in lung disease. Clin Transl Med. 2018; 7(1):39. PMC: 6279673. DOI: 10.1186/s40169-018-0217-2. View

19.

Fanucchi M, Buckpitt A, Murphy M, Storms D, Hammock B, Plopper C . Development of phase II xenobiotic metabolizing enzymes in differentiating murine clara cells. Toxicol Appl Pharmacol. 2000; 168(3):253-67. DOI: 10.1006/taap.2000.9020. View

20.

Wu G, Fang Y, Yang S, Lupton J, Turner N . Glutathione metabolism and its implications for health. J Nutr. 2004; 134(3):489-92. DOI: 10.1093/jn/134.3.489. View