{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:45:00Z","timestamp":1787028300246,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:00:00Z","timestamp":1557705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Fundamental Research Funds for the Central Universities","award":["2019CDXYCH0026"],"award-info":[{"award-number":["2019CDXYCH0026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Soluble sulfide is well known for its toxicity and corrosion for hundreds of years. However, recent studies have demonstrated that hydrogen sulfide (H2S)\u2014a novel gasotransmitter\u2014supports a critical role during neuromodulation, cell proliferation, and cardioprotection for organisms. In particular, soluble sulfide plays multifaceted signaling functions in mammals during oxidative stress processes. However, the specific molecular regulation of soluble sulfide during oxidative stress remains unclear. In this study, Na2S was implemented as a soluble sulfide donor to expose LO2 cells. The 3-(4,5-dimethylthiazolyl-2),-2,5-diphenyltetrazolium bromide (MTT) assay, hydroxyl radical assay, superoxide dismutase (SOD) assay, and glutathione peroxidase (GSH-PX) assay were applied to analyze cytotoxicity, hydroxyl radical levels, SOD and GSH-Px activities, respectively. Soluble sulfide at a concentration 0.01\u20131.0 mM\/L resulted in a marked and concentration-dependent reduction of LO2 cell viability. At low concentrations, sulfide solutions increased SOD activity and GSH-Px activity of LO2 after 24 h exposure, exhibiting a clear hormesis-effect and indicating the protective ability of soluble sulfide against oxidative stress. The decline in SOD and GSH-Px and the increase in hydroxyl radical (0.08\u20131.0 mM\/L) suggested that oxidative damage could be a possible mechanism for sulfide-induced cytotoxicity.<\/jats:p>","DOI":"10.3390\/ijerph16091662","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T11:00:57Z","timestamp":1557745257000},"page":"1662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Oxidative Stress Effects of Soluble Sulfide on Human Hepatocyte Cell Line LO2"],"prefix":"10.3390","volume":"16","author":[{"given":"Ying","family":"Shao","sequence":"first","affiliation":[{"name":"Institute for Environmental Research (Bio V), RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-0532","authenticated-orcid":false,"given":"Zhongli","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Three Gorges Reservoir Eco-environment, Ministry of Education, Chongqing University, Chongqing 400045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yangtze River Water Environment, Ministry of Education, Tongji University, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.microc.2012.09.009","article-title":"A new palladium chelate compound for determination of sulfide","volume":"106","author":"Petruci","year":"2013","journal-title":"Microchem. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.scitotenv.2017.05.225","article-title":"Simultaneous use of caustic and oxygen for efficient sulfide control in sewers","volume":"601\u2013602","author":"Lin","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6046","DOI":"10.3390\/molecules17056046","article-title":"Effect of Soluble Sulfide on the Activity of Luminescent Bacteria","volume":"17","author":"Shao","year":"2012","journal-title":"Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12012-015-9309-z","article-title":"Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility","volume":"16","author":"Sonobe","year":"2016","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1152\/physrev.00017.2011","article-title":"Physiological implications of hydrogen sulfide: A whiff exploration that blossomed","volume":"92","author":"Wang","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"375","DOI":"10.2166\/wst.2008.132","article-title":"Continuous measurement of dissolved sulfide in sewer systems","volume":"57","author":"Corrie","year":"2008","journal-title":"Water Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.niox.2014.01.002","article-title":"The physiological role of hydrogen sulfide and beyond","volume":"41","author":"Kimura","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Aroca, A., Gotor, C., and Romero, L.C. (2018). Hydrogen Sulfide Signaling in Plants: Emerging Roles of Protein Persulfidation. Front. Plant Sci., 9.","DOI":"10.3389\/fpls.2018.01369"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"re2","DOI":"10.1126\/scisignal.268re2","article-title":"Signaling by gasotransmitters","volume":"2","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.tibs.2014.03.003","article-title":"Gasotransmitters: Growing pains and joys","volume":"39","author":"Wang","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17907","DOI":"10.1073\/pnas.0709010104","article-title":"A new gaseous signaling molecule emerges: Cardioprotective role of hydrogen sulfide","volume":"104","author":"Lefer","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","unstructured":"European Science Foundation (2011). European Network on Gasotransmitters, European Science Foundation."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4513","DOI":"10.1073\/pnas.0807974105","article-title":"Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation","volume":"106","author":"Sorrentino","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","first-page":"348","article-title":"New roles for cysteine and transsulfuration enzymes: Production of H2S, a neuromodulator and smooth muscle relaxant","volume":"62","author":"Dominy","year":"2010","journal-title":"Nutr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3109\/0886022X.2011.643365","article-title":"Exogenous Hydrogen Sulfide (H2S) Reduces Blood Pressure and Prevents the Progression of Diabetic Nephropathy in Spontaneously Hypertensive Rats","volume":"34","author":"Ahmad","year":"2012","journal-title":"Ren. Fail."},{"key":"ref_16","first-page":"697","article-title":"H2S, a new neuromodulator","volume":"20","author":"Kamoun","year":"2004","journal-title":"Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.bbrc.2006.10.058","article-title":"Effects of hydrogen sulfide on homocysteine-induced oxidative stress in vascular smooth muscle cells","volume":"351","author":"Yan","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lan, A., Liao, X., Mo, L., Yang, C., Yang, Z., Wang, X., Hu, F., Chen, P., Feng, J., and Zheng, D. (2011). Hydrogen sulfide protects against chemical hypoxia-induced injury by inhibiting ROS-activated ERK1\/2 and p38MAPK signaling pathways in PC12 cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025921"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/jnc.12695","article-title":"Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia","volume":"129","author":"Wang","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/j.1471-4159.2004.02617.x","article-title":"The novel neuromodulator hydrogen sulfide: An endogenous peroxynitrite \u2018scavenger\u2019?","volume":"90","author":"Whiteman","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.bbrc.2004.11.110","article-title":"Hydrogen sulphide: A novel inhibitor of hypochlorous acid-mediated oxidative damage in the brain?","volume":"326","author":"Whiteman","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7237","DOI":"10.3390\/molecules19067237","article-title":"Processing of kansui roots stir-baked with vinegar reduces kansui-induced hepatocyte cytotoxicity by decreasing the contents of toxic terpenoids and regulating the cell apoptosis pathway","volume":"19","author":"Yan","year":"2014","journal-title":"Molecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.etap.2016.01.019","article-title":"Effects of soluble sulfide on zebrafish (Danio rerio) embryonic development","volume":"42","author":"Wu","year":"2016","journal-title":"Environ. Toxicol. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1533\/9781908818195.123","article-title":"Nanotoxicology: Evaluating toxicity potential of drug-nanoparticles","volume":"64","author":"Patravale","year":"2012","journal-title":"Nanopart. Drug Deliv."},{"key":"ref_25","unstructured":"Riss, T.L., Moravec, R.A., Niles, A.L., Benink, H.A., Worzella, T.J., and Minor, L. (2004). Cell Viability Assays\u2014Assay Guidance Manual."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1021\/acs.chemrev.5b00407","article-title":"Superoxide Ion: Generation and Chemical Implications","volume":"116","author":"Hayyan","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0092-8674(01)00524-4","article-title":"Negative Control of p53 by Sir2\u03b1 Promotes Cell Survival under Stress","volume":"107","author":"Luo","year":"2001","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1159\/000430317","article-title":"ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP\/AIF Pathway","volume":"36","author":"Yu","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.biopha.2016.10.015","article-title":"Madecassic Acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress","volume":"84","author":"Yang","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12011-016-0653-z","article-title":"Selenoprotein X Gene Knockdown Aggravated H2O2-Induced Apoptosis in Liver LO2 Cells","volume":"173","author":"Tang","year":"2016","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1046\/j.1471-4159.2000.0752259.x","article-title":"Protective effects of riluzole on dopamine neurons: Involvement of oxidative stress and cellular energy metabolism","volume":"75","author":"Storch","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.mito.2011.01.006","article-title":"Induction of mitochondrial destabilization and necrotic cell death by apolar mitochondria-directed SOD mimetics","volume":"11","author":"Szabo","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/S0891-5849(03)00149-7","article-title":"Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis","volume":"34","author":"Fubini","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0034-5288(18)32219-7","article-title":"Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep","volume":"34","author":"Woolliams","year":"1983","journal-title":"Res. Vet. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_36","first-page":"158","article-title":"Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase","volume":"70","author":"Paglia","year":"1967","journal-title":"J. Lab. Clin. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1242\/jeb.021303","article-title":"Hypotaurine and sulfhydryl-containing antioxidants reduce H2S toxicity in erythrocytes from a marine invertebrate","volume":"211","author":"Ortega","year":"2008","journal-title":"J. Exp. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3109\/10408448409029321","article-title":"A critical review of the literature on hydrogen sulfide toxicity","volume":"13","author":"Beauchamp","year":"1984","journal-title":"CRC Crit. Rev. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s10863-008-9166-6","article-title":"The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: Chemical mechanism and physiological significance","volume":"40","author":"Cooper","year":"2008","journal-title":"J. Bioenergy Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.tox.2004.05.020","article-title":"H2S cytotoxicity mechanism involves reactive oxygen species formation and mitochondrial depolarisation","volume":"203","author":"Eghbal","year":"2004","journal-title":"Toxicology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/03602530600959607","article-title":"Molecular Mechanisms of Hydrogen Sulfide Toxicity","volume":"38","author":"Truong","year":"2006","journal-title":"Drug Metab. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1152\/jn.1993.70.1.81","article-title":"The actions of hydrogen sulfide on dorsal raphe serotonergic neurons in vitro","volume":"70","author":"Kombian","year":"1993","journal-title":"J. Neurophysiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/ajim.4700190505","article-title":"Mortality among sulfide ore miners","volume":"19","author":"Ahlman","year":"1991","journal-title":"Am. J. Ind. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1113\/jphysiol.2003.049478","article-title":"Mitochondrial formation of reactive oxygen species","volume":"552","author":"Turrens","year":"2003","journal-title":"J. Physiol."},{"key":"ref_45","first-page":"3","article-title":"Oxidative stress in bacteria and protein damage by reactive oxygen species","volume":"3","author":"Cabiscol","year":"2010","journal-title":"Int. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.siny.2010.04.003","article-title":"Oxygen toxicity: Chemistry and biology of reactive oxygen species","volume":"15","author":"Buonocore","year":"2010","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0891-5849(01)00724-9","article-title":"Reactive oxygen species, antioxidants, and the mammalian thioredoxin system","volume":"31","author":"Nordberg","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ecoenv.2007.12.016","article-title":"Hydroxyl radical generation and oxidative stress in Carassius auratus liver, exposed to pyrene","volume":"71","author":"Sun","year":"2008","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3164\/jcbn.09-104-2","article-title":"Superoxide anion, uncoupling proteins and Alzheimer\u2019s disease","volume":"46","author":"Wu","year":"2010","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbrc.2012.03.121","article-title":"Hydrogen sulfide decreases the levels of ROS by inhibiting mitochondrial complex IV and increasing SOD activities in cardiomyocytes under ischemia\/reperfusion","volume":"421","author":"Sun","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.redox.2017.11.009","article-title":"Metabolism of Hydrogen Sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by Superoxide Dismutase","volume":"15","author":"Olson","year":"2018","journal-title":"Redox Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative Stress and Antioxidant Defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1042\/CS20170177","article-title":"Oxidative imbalance and kidney damage in spontaneously hypertensive rats: Activation of extrinsic apoptotic pathways","volume":"131","author":"Brunelli","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrurol.2009.49","article-title":"Glutathione S-transferases in kidney and urinary bladder tumors","volume":"6","author":"Simic","year":"2009","journal-title":"Nat. Rev. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2017.09.019","article-title":"Proteomic analysis of the glutathione-deficient LEGSKO mouse lens reveals activation of EMT signaling, loss of lens specific markers, and changes in stress response proteins","volume":"113","author":"Whitson","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.niox.2014.11.006","article-title":"Hydrogen sulfide protects against apoptosis under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes","volume":"46","author":"Wu","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/0003-9861(85)90056-6","article-title":"Inactivation of glutathione peroxidase by superoxide radical","volume":"240","author":"Blum","year":"1985","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.fct.2019.02.037","article-title":"Lutein derived from marigold (Tagetes erecta) petals triggers ROS generation and activates Bax and caspase-3 mediated apoptosis of human cervical carcinoma (HeLa) cells","volume":"127","author":"Gansukh","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1007\/s00595-014-1064-4","article-title":"Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver","volume":"45","author":"Shimada","year":"2015","journal-title":"Surg. Today"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40780-018-0120-4","article-title":"Low concentrations of clarithromycin upregulate cellular antioxidant enzymes and phosphorylation of extracellular signal-regulated kinase in human small airway epithelial cells","volume":"4","author":"Iwayama","year":"2018","journal-title":"J. Pharm. Health Care Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.12659\/MSM.914799","article-title":"Pyridoxamine Treatment of HK-2 Human Proximal Tubular Epithelial Cells Reduces Oxidative Stress and the Inhibition of Autophagy induced by High Glucose Levels","volume":"25","author":"Wang","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jiao, Z.H., Li, M., Feng, Y.X., Shi, J.C., Zhang, J., and Shao, B. (2014). Hormesis Effects of Silver Nanoparticles at Non-Cytotoxic Doses to Human Hepatoma Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102564"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/9\/1662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:51:30Z","timestamp":1760187090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/9\/1662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,13]]},"references-count":62,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["ijerph16091662"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16091662","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,13]]}}}