{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:11:55Z","timestamp":1780089115023,"version":"3.54.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NEI","award":["1R15EY032274-01"],"award-info":[{"award-number":["1R15EY032274-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Hydrogen sulfide (H2S) is an endogenous transmitter with the potential to regulate aqueous humor dynamics and protect retinal neurons from degeneration. The aim of the present study was two-fold: (a) to evaluate the release of H2S from two polysulfides, diallyl disulfide (DADS), and diallyl trisulfide (DATS); and (b) to investigate their ocular hypotensive actions in normotensive male and female rabbits in the presence and absence of GSH. Materials and Methods: H2S was quantified hourly for up to 6 h using a H2S-Biosensor (World Precision Instruments, Sarasota, Fl). Intraocular pressure (IOP) was assessed in normotensive New Zealand Albino rabbits using a pneumotonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY, USA). Results: In the presence of GSH, there was an increase in the in vitro release of H2S produced by DADS and DATS. Both DADS and DATS also caused a dose-dependent reduction in IOP in male and female rabbits, in both treated and untreated eyes. For instance, in male animals, the presence of GSH (3% and 5%) significantly (p &lt; 0.05, n = 5) enhanced the ocular hypotensive action of DADS (2%) and DATS (2%) from 14.02 \u00b1 2.89% to 18.67 \u00b1 5.6% and from 16.22 \u00b1 3.48 to 23.62 \u00b1 5.79%, respectively. Conclusions: GSH enhanced both H2S release and ocular hypotensive action of the polysulfides in a manner that was dependent on the number of sulfur atoms present in each polysulfide. Furthermore, female animals were less sensitive to the IOP-lowering action of the polysulfides, when compared to their male counterparts.<\/jats:p>","DOI":"10.3390\/ph17101408","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T08:53:11Z","timestamp":1729500791000},"page":"1408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glutathione Modulates Hydrogen Sulfide Release and the Ocular Hypotensive Action of Diallyl Polysulfide Compounds"],"prefix":"10.3390","volume":"17","author":[{"given":"Susmit","family":"Mhatre","sequence":"first","affiliation":[{"name":"Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA"},{"name":"Cell and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rai","family":"Anjali","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA"},{"name":"Comparative Biomedical Sciences Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pulkit","family":"Sahai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Auden","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somnath","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-7266","authenticated-orcid":false,"given":"Ya Fatou","family":"Njie Mbye","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunny E.","family":"Ohia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Opere","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sciences, School of Pharmacy and Health Professionals, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"ref_1","first-page":"492","article-title":"Physiological role of hydrogen sulfide and polysulfide in the central nervous system","volume":"63","author":"Kimura","year":"2013","journal-title":"Neuro-Chem. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator","volume":"16","author":"Abe","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s11064-018-2471-5","article-title":"Comparative Effects of Hydrogen Sul-fide-Releasing Compounds on [3H]D-Aspartate Release from Bovine Isolated Retinae","volume":"43","author":"Bankhele","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/jop.2017.0077","article-title":"Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy","volume":"34","author":"Ohia","year":"2018","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1089\/ars.2011.4345","article-title":"Hydrogen sulfide is a signaling molecule and a cytoprotectant","volume":"17","author":"Kimura","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1096\/fj.04-1815fje","article-title":"Hydrogen sulfide protects neurons from oxidative stress","volume":"18","author":"Kimura","year":"2004","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15560","DOI":"10.1073\/pnas.0705891104","article-title":"Hydrogen sulfide attenuates myo-cardial ischemia-reperfusion injury by preservation of mitochondrial function","volume":"104","author":"Elrod","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1073\/pnas.1321871111","article-title":"Hydrogen sulfide cytopro-tective signaling is endothelial nitric oxide synthase-nitric oxide dependent","volume":"111","author":"King","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1006\/bbrc.1997.6878","article-title":"The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide","volume":"237","author":"Hosoki","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1124\/mol.105.017467","article-title":"Direct Stimulation of KATP Channels by Exogenous and Endogenous Hydrogen Sulfide in Vascular Smooth Muscle Cells","volume":"68","author":"Tang","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"H2316","DOI":"10.1152\/ajpheart.00331.2004","article-title":"Hydrogen sulfide-induced relaxation of resistance mes-enteric artery beds of rats","volume":"287","author":"Cheng","year":"2004","journal-title":"AJP-Heart Circ. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1161\/CIRCRESAHA.111.240242","article-title":"Hydrogen sulfide as endotheli-um-derived hyperpolarizing factor sulfhydrates potassium channels","volume":"109","author":"Mustafa","year":"2011","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1096\/fj.02-0211hyp","article-title":"Two\u2019s company, three\u2019s a crowd: Can H2S be the third endogenous gaseous transmitter?","volume":"16","author":"Wang","year":"2002","journal-title":"FASEB J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1126\/science.1162667","article-title":"H2S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine \u03b3-Lyase","volume":"322","author":"Yang","year":"2008","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.1093\/emboj\/20.21.6008","article-title":"The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener","volume":"20","author":"Zhao","year":"2001","journal-title":"EMBO J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"H474","DOI":"10.1152\/ajpheart.00013.2002","article-title":"H2S-induced vasorelaxation and underlying cellular and molecular mechanisms","volume":"283","author":"Zhao","year":"2002","journal-title":"AJP-Heart Circ. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"ra86","DOI":"10.1126\/scisignal.2002329","article-title":"H2S-Induced Sulfhydration of the Phosphatase PTP1B and Its Role in the Endoplasmic Reticulum Stress Response","volume":"4","author":"Krishnan","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1096\/fj.04-3583fje","article-title":"Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse","volume":"19","author":"Li","year":"2005","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"ra72","DOI":"10.1126\/scisignal.2000464","article-title":"H2S Signals Through Protein S-Sulfhydration","volume":"2","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.freeradbiomed.2006.03.021","article-title":"Hydrogen sulfide inhibits nitric oxide pro-duction and nuclear factor-\u03baB via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide","volume":"41","author":"Oh","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molcel.2011.10.021","article-title":"Hydrogen sulfide-linked sulfhydration of NF-\u03baB mediates its antiapoptotic actions","volume":"45","author":"Sen","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1096\/fj.06-6270fje","article-title":"Hydrogen sulfide is an en-dogenous modulator of leukocyte-mediated inflammation","volume":"20","author":"Zanardo","year":"2006","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12474","DOI":"10.1073\/pnas.1306241110","article-title":"Tumor-derived hydrogen sulfide, produced by cystathionine-\u03b2-synthase, stimulates bioenergetics, cell proliferation, and angio-genesis in colon cancer","volume":"110","author":"Szabo","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S1096-4959(01)00309-8","article-title":"Sulfide oxidation coupled to ATP synthesis in chicken liver mitochondria","volume":"129","author":"Yong","year":"2001","journal-title":"Com-parative Biochemistry and Physiology Part B: Biochem. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.niox.2017.04.010","article-title":"Hydrogen sulfide attenuates cardiac injury in takotsubo cardiomyopathy by alleviating oxidative stress","volume":"67","author":"Zhang","year":"2017","journal-title":"Nitric Oxide."},{"key":"ref_27","first-page":"371","article-title":"Cystathionase activity in rat tissues during development","volume":"23","author":"De","year":"1974","journal-title":"Ital. J. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.exer.2006.04.001","article-title":"The distribution of cystathionine beta-synthase (CBS) in the ey: Implication of the presence of a trans-sulfuration pathway for oxidative stress defense","volume":"83","author":"Persa","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/cne.21468","article-title":"Comparative localization of cystathionine beta-synthase and cystathionine gamma-lyase in retina: Differences between amphibians and mannals","volume":"505","author":"Pong","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_30","unstructured":"Carmel, R., and Jacobsen, D.W. (2001). Cystathionine B synthase and its deficiency. Homocysteine in Health and Disease, Cambridge University Press."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115458","DOI":"10.1016\/j.ab.2024.115458","article-title":"Analysis and characterization of sulfane sulfur","volume":"687","author":"Koike","year":"2024","journal-title":"Anal. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Subramanian, S., Nandagopal, G., Nordin, S.A., and Joseph, N. (2020). Prevailing knowledge on the bioavailability and biological activities of sulphur compounds from alliums: A potential drug candidate. Molecules, 25.","DOI":"10.3390\/molecules25184111"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17977","DOI":"10.1073\/pnas.0705710104","article-title":"Hydrogen sulfide mediates the vasoactivity of garlic","volume":"104","author":"Benavides","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"943967","DOI":"10.3389\/fphar.2022.943967","article-title":"Diallyl Disulfide: A Bioac-tive Garlic Compound with Anticancer Potential","volume":"13","author":"Mitra","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Puccinelli, M.T., and Stan, S.D. (2017). Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081645"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8508906","DOI":"10.1155\/2020\/8508906","article-title":"Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carra-geenan Injection-Induced Paw Edema in Mice","volume":"2020","author":"Zhang","year":"2020","journal-title":"Mediators Inflamm."},{"key":"ref_37","first-page":"1","article-title":"Protective Action of Hydrogen Sulfide-Releasing Compounds against Oxidative Stress-Induced Cataract Formation in Cultured Bovine Lenses","volume":"19","author":"Heruye","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Heruye, S.H., Maffofou Nkenyi, L.N., Singh, N.U., Yalzadeh, D., Ngele, K.K., Njie-Mbye, Y.F., Ohia, S.E., and Opere, C.A. (2020). Current Trends in the Pharmacotherapy of Cataracts. Pharmaceuticals, 13.","DOI":"10.37247\/UP.1.2020.4"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1124\/pr.117.014050","article-title":"International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors","volume":"69","author":"Szabo","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1007\/s11064-023-03887-y","article-title":"Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges","volume":"48","author":"Sharif","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1021\/acs.orglett.5b01962","article-title":"Diallyl Trisulfide Is a Fast H2S Donor, but Diallyl Disulfide Is a Slow One: The Reaction Pathways and Intermediates of Glutathione with Polysulfides","volume":"17","author":"Liang","year":"2015","journal-title":"Org. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3109\/02713688408997189","article-title":"Gluthathione and ocular photobiology","volume":"3","author":"Megaw","year":"1984","journal-title":"Curr. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/02713680500477347","article-title":"Glutathione-Related Enzymes and the Eye","volume":"31","author":"Ganea","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-019-1525-1","article-title":"Hydrogen sulfide: A gaseous signaling molecule modulates tissue homeo-stasis: Implications in ophthalmic diseases","volume":"10","author":"Han","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e85984","DOI":"10.1371\/journal.pone.0085984","article-title":"Keap1 Cysteine 288 as a Potential Target for Diallyl Trisulfide-Induced Nrf2 Activation","volume":"9","author":"Kim","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/vop.12020","article-title":"Twenty-four-hour measurement of IOP in rabbits using rebound tonometer","volume":"16","author":"Wang","year":"2013","journal-title":"Vet. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3109\/02713688908997574","article-title":"Interaction Between Progesterone and Mifepristone on Intraocular Pressure in Rabbits","volume":"8","author":"Green","year":"1989","journal-title":"Curr. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1053\/rvsc.1998.0300","article-title":"The effect of elevated progesterone levels on intraocular pressure in lions (Panthera leo)","volume":"67","author":"Ofri","year":"1999","journal-title":"Res. Vet. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2144\/btn-2023-0075","article-title":"Comparison of Colorimetric, Spectroscopic and Electrochemical Techniques for Quantification of Hydrogen Sulfide","volume":"76","author":"Mhatre","year":"2023","journal-title":"BioTechniques"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/10\/1408\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:17:33Z","timestamp":1760113053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/10\/1408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,21]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ph17101408"],"URL":"https:\/\/doi.org\/10.3390\/ph17101408","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,21]]}}}