{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:21:46Z","timestamp":1775175706653,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001109","name":"Flinn Foundation","doi-asserted-by":"publisher","award":["#22-06454"],"award-info":[{"award-number":["#22-06454"]}],"id":[{"id":"10.13039\/100001109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ruthenium chloride (RuCl3) is widely utilized for synthesis and catalysis of numerous compounds in academia and industry and is utilized as a key molecule in a variety of compounds with medical applications. Interestingly, RuCl3 has been demonstrated to modulate human plasmatic coagulation and serves as a constituent of a compounded inorganic antivenom that neutralizes the coagulopathic effects of snake venom in vitro and in vivo. Using thrombelastography, this investigation sought to determine if RuCl3 inhibition of the fibrinogenolytic effects of Crotalus atrox venom could be modulated by vehicle composition in human plasma. Venom was exposed to RuCl3 in 0.9% NaCl, phosphate-buffered saline (PBS), or 0.9% NaCl containing 1% dimethyl sulfoxide (DMSO). RuCl3 inhibited venom-mediated delay in the onset of thrombus formation, decreased clot growth velocity, and decreased clot strength. PBS and DMSO enhanced the effects of RuCl3. It is concluded that while a Ru-based cation is responsible for significant inhibition of venom activity, a combination of Ru-based ions containing phosphate and DMSO enhances RuCl3-mediated venom inhibition. Additional investigation is indicated to determine what specific Ru-containing molecules cause venom inhibition and what other combinations of inorganic\/organic compounds may enhance the antivenom effects of RuCl3.<\/jats:p>","DOI":"10.3390\/ijms25126426","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T12:11:00Z","timestamp":1718107860000},"page":"6426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phosphate-Buffered Saline and Dimethyl Sulfoxide Enhance the Antivenom Action of Ruthenium Chloride against Crotalus atrox Venom in Human Plasma\u2014A Preliminary Report"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-9883","authenticated-orcid":false,"given":"Vance G.","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The University of Arizona College of Medicine, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1021\/ol049097a","article-title":"Ruthenium-catalyzed decarboxylative allylation of nonstabilized ketone enolates","volume":"6","author":"Burger","year":"2004","journal-title":"Org. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1039\/b403616f","article-title":"Ruthenium\/chloride catalytic system for conjugate addition of terminal alkynes to acrylate esters","volume":"11","author":"Nishimura","year":"2004","journal-title":"Chem. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1021\/jo048020x","article-title":"RuCl3\/CeCl3\/NaIO4: A new bimetallic oxidation system for the mild and efficient dihydroxylation of unreactive olefins","volume":"70","author":"Plietker","year":"2005","journal-title":"J. Org. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1021\/jo0526385","article-title":"An efficient stereoselective dihydroxylation of glycals using a bimetallic system, RuCl3\/CeCl3\/NaIO4","volume":"71","author":"Tiwari","year":"2006","journal-title":"J. Org. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9912","DOI":"10.1021\/jo062073s","article-title":"RuCl3-catalyzed oxidation of iodoarenes with peracetic acid: New facile preparation of iodylarenes","volume":"71","author":"Koposov","year":"2006","journal-title":"J. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3218","DOI":"10.1002\/chem.200501384","article-title":"The importance of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones","volume":"12","author":"Zaitsev","year":"2006","journal-title":"Chemistry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1021\/ol062631p","article-title":"RuCl3\/PPh3: An efficient combination for the preparation of chiral 1,3-anti-diols through catalytic hydrogenation","volume":"9","author":"Labeeuw","year":"2007","journal-title":"Org. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.3390\/molecules13123246","article-title":"Dodecatungstophosphoric acid (H3PW12O40), samarium and ruthenium (III) chloride catalyzed synthesis of unsaturated 2-phenyl-5(4H)-oxazolone derivatives under solvent-free conditions","volume":"13","author":"Tikdari","year":"2008","journal-title":"Molecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3762\/bjoc.4.53","article-title":"Chemoselective reduction of aldehydes by ruthenium trichloride and resin-bound formats","volume":"4","author":"Basu","year":"2008","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5471","DOI":"10.1021\/jo901045g","article-title":"Platinum and ruthenium chloride-catalyzed cycloisomerization of 1-alkyl-2-ethynylbenzenes: Interception of pi-activated alkynes with a benzylic C-H bond","volume":"74","author":"Tobisu","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.3390\/molecules14093528","article-title":"Ruthenium(III) chloride catalyzed acylation of alcohols, phenols, and thiols in room temperature ionic liquids","volume":"14","author":"Xi","year":"2009","journal-title":"Molecules"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1021\/ol101038c","article-title":"Ruthenium chloride as an efficient catalytic precursor for hydroarylation reactions via C-H bond activation","volume":"12","author":"Simon","year":"2010","journal-title":"Org. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/cssc.201200503","article-title":"Selective conversion of polyenes to monoenes by RuCl3-catalyzed transfer hydrogenation: The case of cashew nutshell liquid","volume":"5","author":"Perdriau","year":"2012","journal-title":"ChemSusChem"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7720","DOI":"10.1039\/C5CP00231A","article-title":"Influence of chlorine coordination number on the catalytic mechanism of ruthenium chloride catalysts in the acetylene hydrochlorination reaction: A DFT study","volume":"17","author":"Han","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11326","DOI":"10.1038\/ncomms11326","article-title":"Highly selective hydrogenation of arenes using nanostructured ruthenium catalysts modified with a carbon-nitrogen matrix","volume":"7","author":"Cui","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.biortech.2019.01.120","article-title":"Ruthenium trichloride catalyzed conversion of cellulose into 5-hydroxymethylfurfural in biphasic system","volume":"279","author":"Yan","year":"2019","journal-title":"Bioresour. Technol."},{"key":"ref_17","first-page":"2181","article-title":"Scanning electron microscope, freeze etching and glycosaminoglycan cytochemical studies of the cerebellar climbing fiber system","volume":"2","year":"1988","journal-title":"Scanning Microsc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1039\/b309913j","article-title":"The effect of ruthenium(III) chloride on the formation of protonated parent ions in electrospray mass spectrometry","volume":"21","author":"Stark","year":"2003","journal-title":"Chem. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"890","DOI":"10.3389\/fphar.2019.00890","article-title":"Ruthenium Chloride-Induced Oxidative Cyclization of Trans-Resveratrol to (\u00b1)-\u03b5-Viniferin and Antimicrobial and Antibiofilm Activity Against Streptococcus pneumoniae","volume":"10","author":"Yadav","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"de Oliveira, D.M., Santos, I.A., Martins, D.O.S., Gon\u00e7alves, Y.G., Cardoso-Sousa, L., Sabino-Silva, R., Von Poelhsitz, G., Franca, E.F., Nicolau-Junior, N., and Pacca, C.C. (2020). Organometallic Complex Strongly Impairs Chikungunya Virus Entry to the Host Cells. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.608924"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Labach, D.S., Kohio, H.P., Tse, E.A., Paparisto, E., Friesen, N.J., Pankovich, J., Bazett, M., and Barr, S.D. (2023). The Metallodrug BOLD-100 Is a Potent Inhibitor of SARS-CoV-2 Replication and Has Broad-Acting Antiviral Activity. Biomolecules, 13.","DOI":"10.3390\/biom13071095"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"D\u2019Amato, A., Mariconda, A., Iacopetta, D., Ceramella, J., Catalano, A., Sinicropi, M.S., and Longo, P. (2023). Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections. Pharmaceuticals, 16.","DOI":"10.3390\/ph16121729"},{"key":"ref_23","first-page":"353","article-title":"Ruthenium-based compounds and tumour growth control (review)","volume":"17","author":"Sava","year":"2000","journal-title":"Int. J. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.1021\/ic8005579","article-title":"Ruthenium(III) chloride complex with a tridentate bis(arylimino)pyridine ligand: Synthesis, spectra, X-ray structure, 9-ethylguanine binding pattern, and in vitro cytotoxicity","volume":"47","author":"Maheswari","year":"2008","journal-title":"Inorg. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0014-2999(99)00095-3","article-title":"Antinociceptive properties and nitric oxide synthase inhibitory action of new ruthenium complexes","volume":"369","author":"Beirith","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1474-8673.2008.00423.x","article-title":"Antinociceptive effect of a ruthenium complex in mice","volume":"28","author":"Cristiano","year":"2008","journal-title":"Auton. Autacoid Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pbb.2013.02.006","article-title":"The ruthenium NO donor, [Ru(bpy)2(NO)SO3](PF6), inhibits inflammatory pain: Involvement of TRPV1 and cGMP\/PKG\/ATP-sensitive potassium channel signaling pathway","volume":"105","author":"Mizokami","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3389\/fphar.2019.00229","article-title":"[Ru(bpy)2(NO)SO3](PF6), a Nitric Oxide Donating Ruthenium Complex, Reduces Gout Arthritis in Mice","volume":"10","author":"Rossaneis","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s44319-023-00050-0","article-title":"Molecular details of ruthenium red pore block in TRPV channels","volume":"25","author":"Pumroy","year":"2024","journal-title":"EMBO Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s11239-020-02373-4","article-title":"Platinoid effects on human plasmatic coagulation kinetics: A viscoelastic analysis","volume":"51","author":"Nielsen","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nielsen, V.G. (2021). Modulation of Diverse Procoagulant Venom Activities by Combinations of Platinoid Compounds. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094612"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1007\/s11239-021-02479-3","article-title":"Ruthenium chloride inhibits the anticoagulant activity of the phospholipase A2-dependent neurotoxin of Mojave rattlesnake Type A venom","volume":"52","author":"Nielsen","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nielsen, V.G. (2023). Novel Toxicodynamic Model of Subcutaneous Envenomation to Characterize Snake Venom Coagulopathies and Assess the Efficacy of Site-Directed Inorganic Antivenoms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813939"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/MBC.0000000000001294","article-title":"Ruthenium-based antivenom attenuates Crotalus atrox venom mediated coagulopathy in rabbits","volume":"35","author":"Nielsen","year":"2024","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nielsen, V.G. (2020). Ruthenium, Not Carbon Monoxide, Inhibits the Procoagulant Activity of Atheris, Echis, and Pseudonaja Venoms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082970"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1155\/MBD.1994.41","article-title":"Water-Soluble Ruthenium(III)-Dimethyl Sulfoxide Complexes: Chemical Behaviour and Pharmaceutical Properties","volume":"1","author":"Mestroni","year":"1994","journal-title":"Met. Based Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood.V63.1.1.1","article-title":"Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake (Crotalus atrox)","volume":"63","author":"Budzynski","year":"1984","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/MBC.0000000000000440","article-title":"Iron and carbon monoxide attenuate degradation of plasmatic coagulation by Crotalus atrox venom","volume":"27","author":"Nielsen","year":"2016","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s11239-019-01980-0","article-title":"The anticoagulant effect of Apis mellifera phospholipase A2 is inhibited by CORM-2 via a carbon monoxide-independent mechanism","volume":"49","author":"Nielsen","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.redox.2018.06.008","article-title":"A thiol-reactive Ru(II) ion, not CO release, underlies the potent antimicrobial and cytotoxic properties of CO-releasing molecule-3","volume":"18","author":"Southam","year":"2018","journal-title":"Redox. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s11239-019-01887-w","article-title":"Heme and carbon monoxide modulate the anticoagulant activity of Mojave rattlesnake venom type A and B","volume":"48","author":"Nielsen","year":"2019","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/bcpt.12846","article-title":"Crotalus atrox venom exposed to carbon monoxide has decreased fibrinogenolytic activity in vivo in rabbits","volume":"122","author":"Nielsen","year":"2018","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/MBC.0b013e3280111a8e","article-title":"Thrombelastographic measures of clot propagation: A comparison of alpha to maximum rate of thrombus generation","volume":"18","author":"Ellis","year":"2007","journal-title":"Blood Coagul. Fibrinolysis"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/12\/6426\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:56:47Z","timestamp":1760108207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/12\/6426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,11]]},"references-count":43,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25126426"],"URL":"https:\/\/doi.org\/10.3390\/ijms25126426","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,11]]}}}