Cytotoxicity and Oxidative Stress Induced by Atmospheric Mono-nitrophenols in Human Lung Cells

Overview

Journal Environ Pollut

Specialty Environmental Health

Date 2022 Feb 26

PMID 35217136

Authors

Faria Khan

Mohammed Jaoui

Krzysztof Rudzinski

Karina Kwapiszewska

Alicia Martinez-Romero

Domingo Gil-Casanova

Michael Lewandowski

Tadeusz E Kleindienst

John H Offenberg

Jonathan D Krug

Jason D Surratt

Rafal Szmigielski

Affiliations

Soon will be listed here.

Abstract

Nitrophenols (NPs) are hazardous pollutants found in various environmental matrices, including ambient fine particulate matter (PM), agricultural residues, rainwater, wildfires, and industrial wastes. This study showed for the first time the effect of three pure nitrophenols and their mixture on human lung cells to provide basic understanding of the NP influence on cell elements and processes. We identified NPs in ambient PM and secondary organic aerosol (SOA) particles generated from the photooxidation of monocyclic aromatic hydrocarbons in the U.S. EPA smog chamber. We assessed the toxicity of identified NPs and their equimolar mixture in normal bronchial epithelial (BEAS-2B) and alveolar epithelial cancer (A549) lung cell lines. The inhibitory concentration-50 (IC) values were highest and lowest in BEAS-2B cells treated with 2-nitrophenol (2NP) and 4-nitrophenol (4NP), respectively, at 24 h of exposure. The lactate dehydrogenase (LDH) assay showed that 4NP, the most abundant NP we identified in PM, was the most cytotoxic NP examined in both cell lines. The annexin-V/fluorescein isothiocyanate (FITC) analysis showed that the populations of late apoptotic/necrotic BEAS-2B and A549 cells exposed to 3NP, 4NP, and NP equimolar mixture increased between 24 and 48 h. Cellular reactive oxygen species (ROS) buildup led to cellular death post exposure to 3NP, 4NP and the NP mixtures, while 2NP induced the lowest ROS buildup. An increased mitochondrial ROS signal following NP exposure occurred only in BEAS-2B cells. The tetramethylrhodamine, methyl ester, perchlorate (TMRM) assay showed that exposed cells exhibited collapse of the mitochondrial membrane potential. TMRM signals decreased significantly only in BEAS-2B cells, and most strongly with 4NP exposures. Our results suggest that acute atmospheric exposures to NPs may be toxic at high concentrations, but not at ambient PM concentrations. Further chronic studies with NP and NP-containing PM are warranted to assess their contribution to lung pathologies.

Citing Articles

Secondary Organic Aerosol Generated from Biomass Burning Emitted Phenolic Compounds: Oxidative Potential, Reactive Oxygen Species, and Cytotoxicity.

Fang Z, Lai A, Cai D, Li C, Carmieli R, Chen J Environ Sci Technol. 2024; 58(19):8194-8206.

PMID: 38683689 PMC: 11097630. DOI: 10.1021/acs.est.3c09903.

The Role of Aqueous Solvation on the Intersystem Crossing of Nitrophenols.

Vandaele E, Malis M, Luber S J Chem Theory Comput. 2024; 20(8):3258-3272.

PMID: 38606908 PMC: 11044273. DOI: 10.1021/acs.jctc.3c01400.

References

Zhang S, Li X, Xie F, Liu K, Liu H, Xie J . Evaluation of whole cigarette smoke induced oxidative stress in A549 and BEAS-2B cells. Environ Toxicol Pharmacol. 2017; 54:40-47. DOI: 10.1016/j.etap.2017.06.023. View

Kuhlbrandt W . Structure and function of mitochondrial membrane protein complexes. BMC Biol. 2015; 13:89. PMC: 4625866. DOI: 10.1186/s12915-015-0201-x. View

Fink S, Cookson B . Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005; 73(4):1907-16. PMC: 1087413. DOI: 10.1128/IAI.73.4.1907-1916.2005. View

LeGrand C, Bour J, Jacob C, Capiaumont J, Martial A, Marc A . Lactate dehydrogenase (LDH) activity of the cultured eukaryotic cells as marker of the number of dead cells in the medium [corrected]. J Biotechnol. 1992; 25(3):231-43. DOI: 10.1016/0168-1656(92)90158-6. View

Badran G, Verdin A, Grare C, Abbas I, Achour D, Ledoux F . Toxicological appraisal of the chemical fractions of ambient fine (PM) and quasi-ultrafine (PM) particles in human bronchial epithelial BEAS-2B cells. Environ Pollut. 2021; 263(Pt A):114620. DOI: 10.1016/j.envpol.2020.114620. View

An J, Zhou Q, Wu M, Wang L, Zhong Y, Feng J . Interactions between oxidative stress, autophagy and apoptosis in A549 cells treated with aged black carbon. Toxicol In Vitro. 2018; 54:67-74. DOI: 10.1016/j.tiv.2018.09.008. View

Pan L, Wu S, Li H, Xu J, Dong W, Shan J . The short-term effects of indoor size-fractioned particulate matter and black carbon on cardiac autonomic function in COPD patients. Environ Int. 2018; 112:261-268. DOI: 10.1016/j.envint.2017.12.037. View

Majewska M, Khan F, Pieta I, Wroblewska A, Szmigielski R, Pieta P . Toxicity of selected airborne nitrophenols on eukaryotic cell membrane models. Chemosphere. 2020; 266:128996. DOI: 10.1016/j.chemosphere.2020.128996. View

Lin Y, Arashiro M, Clapp P, Cui T, Sexton K, Vizuete W . Gene Expression Profiling in Human Lung Cells Exposed to Isoprene-Derived Secondary Organic Aerosol. Environ Sci Technol. 2017; 51(14):8166-8175. PMC: 5610912. DOI: 10.1021/acs.est.7b01967. View

10.

Xie M, Chen X, Holder A, Hays M, Lewandowski M, Offenberg J . Light absorption of organic carbon and its sources at a southeastern U.S. location in summer. Environ Pollut. 2018; 244:38-46. PMC: 6697000. DOI: 10.1016/j.envpol.2018.09.125. View

11.

Lin P, Aiona P, Li Y, Shiraiwa M, Laskin J, Nizkorodov S . Molecular Characterization of Brown Carbon in Biomass Burning Aerosol Particles. Environ Sci Technol. 2016; 50(21):11815-11824. DOI: 10.1021/acs.est.6b03024. View

12.

Vernot E, MACEWEN J, Haun C, Kinkead E . Acute toxicity and skin corrosion data for some organic and inorganic compounds and aqueous solutions. Toxicol Appl Pharmacol. 1977; 42(2):417-23. DOI: 10.1016/0041-008x(77)90019-9. View

13.

Khan F, Kwapiszewska K, Zhang Y, Chen Y, Lambe A, Kolodziejczyk A . Toxicological Responses of α-Pinene-Derived Secondary Organic Aerosol and Its Molecular Tracers in Human Lung Cell Lines. Chem Res Toxicol. 2021; 34(3):817-832. PMC: 7967287. DOI: 10.1021/acs.chemrestox.0c00409. View

14.

Cecinato A, Di Palo V, Pomata D, Sciano M, Possanzini M . Measurement of phase-distributed nitrophenols in Rome ambient air. Chemosphere. 2005; 59(5):679-83. DOI: 10.1016/j.chemosphere.2004.10.045. View

15.

Martindale J, Holbrook N . Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol. 2002; 192(1):1-15. DOI: 10.1002/jcp.10119. View

16.

McDonald J, Doyle-Eisele M, Campen M, Seagrave J, Holmes T, Lund A . Cardiopulmonary response to inhalation of biogenic secondary organic aerosol. Inhal Toxicol. 2010; 22(3):253-65. DOI: 10.3109/08958370903148114. View

17.

Xie M, Chen X, Hays M, Holder A . Composition and light absorption of N-containing aromatic compounds in organic aerosols from laboratory biomass burning. Atmos Chem Phys. 2019; 19(5):2899-2915. PMC: 6733279. DOI: 10.5194/acp-19-2899-2019. View

18.

Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4):495-516. PMC: 2117903. DOI: 10.1080/01926230701320337. View

19.

Laskin A, Laskin J, Nizkorodov S . Chemistry of atmospheric brown carbon. Chem Rev. 2015; 115(10):4335-82. DOI: 10.1021/cr5006167. View

20.

Calas A, Uzu G, Martins J, Voisin D, Spadini L, Lacroix T . The importance of simulated lung fluid (SLF) extractions for a more relevant evaluation of the oxidative potential of particulate matter. Sci Rep. 2017; 7(1):11617. PMC: 5599505. DOI: 10.1038/s41598-017-11979-3. View