{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T02:48:53Z","timestamp":1775616533984,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background. The venom of Loxoscelesrufescens (L.r.), also known as the violin and\/or brown spider, contains a wide variety of proteins and can induce a complex, intense, and uncontrolled inflammatory response, hemolysis, thrombocytopenia, dermo-necrosis, and renal failure. Studies have postulated the efficacy of hyperbaric oxygen therapy (HBOT) for Loxosceles bites. However, data describing the use and beneficial effects of HBO are, to date, relatively scarce. Only a few cases of Loxosceles bites in Northern Italy have been documented, and there is no laboratory test available for the diagnosis. Objectives. We present seven cases (aged 54.5 \u00b1 4.2 years) of patients who presented to the emergency room (E.R.) of Niguarda Hospital in Milan from March to October 2022. Methods. Blood and urine samples were collected and biomarkers of oxidative stress (OxS) (reactive oxygen species (ROS), total antioxidant capacity (TAC), lipid peroxidation (8iso-PFG2\u03b1), DNA damage (8-OH-dG)), inflammation (IL-6, IL-1\u03b2, TNF-\u03b1, sICAM1), and renal function (creatinine, neopterin, uric acid) before (T0), during (T1, T2), and after (1\u20132 wk T3\u2013T4; 1 month T5) the HBOT treatment (US Navy Treatment Table 15 protocol) were studied. Results. At T0, patients showed a significant unbalance of OxS; high levels of ROS, 8-isoPGF2\u03b1, and inflammatory status (IL-6, TNF-\u03b1; sICAM); and a low level of antioxidant capacity. At the end of HBOT (T2), a significant reduction in Oxy-inflammation levels over time\u20148-iso \u221226%, 8-OH-dG \u22129%, IL-6 \u221271%, IL-1b\u03b2 \u221212%, TNF-\u03b1 \u221213%, and sICAM1 \u221217%\u2014associated with clinical improvement was shown. Conclusions. These reductions, along with those in renal function markers, mirrored the observed improvement in the evolution of the skin lesion and the patients\u2019 self-reported general wellness and pain. In conclusion, HBOT should be considered a valuable therapeutic tool after L.r. bites.<\/jats:p>","DOI":"10.3390\/metabo15070470","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T10:26:53Z","timestamp":1752229613000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Adjuvant Effect of Hyperbaric Oxygenation for Loxosceles rufescens Bite: A Case Series"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-2690","authenticated-orcid":false,"given":"Simona","family":"Mrakic-Sposta","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"},{"name":"ASST Grande Ospedale Metropolitano Niguarda, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0277-163X","authenticated-orcid":false,"given":"Alessandra","family":"Vezzoli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"},{"name":"ASST Grande Ospedale Metropolitano Niguarda, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Graci","sequence":"additional","affiliation":[{"name":"ASST Grande Ospedale Metropolitano Niguarda, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maristella","family":"Gussoni","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attilio","family":"Cimmino","sequence":"additional","affiliation":[{"name":"ASST Grande Ospedale Metropolitano Niguarda, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Dellanoce","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council (IFC-CNR), Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"},{"name":"ASST Grande Ospedale Metropolitano Niguarda, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3548-1097","authenticated-orcid":false,"given":"Enrico Maria","family":"Camporesi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Sesana","sequence":"additional","affiliation":[{"name":"ASST Grande Ospedale Metropolitano Niguarda, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6595-7944","authenticated-orcid":false,"given":"Gerardo","family":"Bosco","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxicon.2017.04.007","article-title":"Distribution and medical aspects of Loxosceles rufescens, one of the most invasive spiders of the world Araneae: Sicariidae","volume":"132","author":"Nentwig","year":"2017","journal-title":"Toxicon"},{"key":"ref_2","unstructured":"World Spider Catalog World Spider Catalog, Available online: http:\/\/wsc.nmbe.ch."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0196-0644(87)80738-2","article-title":"The diagnosis and treatment of brown recluse spider bites","volume":"16","author":"Rees","year":"1987","journal-title":"Ann. Emerg. Med."},{"key":"ref_4","unstructured":"Anoka, I.A., Robb, E.L., and Baker, M.B. (2022). Brown Recluse Spider Toxicity. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40409-017-0097-8","article-title":"Highlights in the knowledge of brown spider toxins","volume":"23","author":"Wille","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/00000441-199210000-00008","article-title":"Loxoscelism","volume":"304","author":"Futrell","year":"1992","journal-title":"Am. J. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1684\/ejd.2024.4700","article-title":"Necrotic ulcers caused by Loxosceles rufescens bites: A report of seven patients and scanning electron microscopy of the spider","volume":"34","author":"Veraldi","year":"2024","journal-title":"Eur. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.clindermatol.2005.11.006","article-title":"Loxoscelism","volume":"24","author":"Swanson","year":"2006","journal-title":"Clin Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0140-6736(09)61754-2","article-title":"Snake bite","volume":"375","author":"Warrell","year":"2010","journal-title":"Lancet"},{"key":"ref_10","first-page":"390","article-title":"Dog bite wounds: Bacterial complications and tissue necrosis","volume":"52","author":"Garvey","year":"2002","journal-title":"J. Trauma"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Boia-Ferreira, M., Moreno, K.G., Bas\u00edlio, A.B.C., da Silva, L.P., Vuitika, L., Soley, B., Wille, A.C.M., Donatti, L., Barbaro, K.C., and Chaim, O.M. (2019). Correction: Boia-Ferreira et al. TCTP fromLoxosceles Intermedia(Brown Spider) Venom Contributes to the Allergic and Inflammatory Response of Cutaneous Loxoscelism. Cells, 8.","DOI":"10.3390\/cells8121489"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1001\/jama.1983.03340050060033","article-title":"Dapsone treatment of a brown recluse bite","volume":"250","author":"King","year":"1983","journal-title":"J. Am. Med. Assoc."},{"key":"ref_13","first-page":"e20190100","article-title":"Spider bites of medical significance in the Mediterranean area: Misdiagnosis, clinical features and management","volume":"26","author":"Fusto","year":"2020","journal-title":"J. Venom. Anim. Toxins incl. Trop. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"da Silva, T.P., de Castro, F.J., Vuitika, L., Polli, N.L.C., Antunes, B.C., B\u00f3ia-Ferreira, M., Minozzo, J.C., Mariutti, R.B., Matsubara, F.H., and Arni, R.K. (2021). Brown Spiders\u2019 Phospholipases-D with Potential Therapeutic Applications: Functional Assessment of Mutant Isoforms. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030320"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxicon.2014.02.023","article-title":"Recent Advances in the Understanding of Brown Spider Venoms: From the Biology of Spiders to the Molecular Mechanisms of Toxins","volume":"83","author":"Gremskim","year":"2014","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gremskim, L.H., Da Justam, H.C., Da Silvam, T.P., Pollim, N.L.C., Antunesm, B.C., and Minozzom, J.C. (2020). Forty Years of the Description of Brown Spider Venom Phospholipases-D. Toxins, 12.","DOI":"10.3390\/toxins12030164"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/15563650.2019.1578367","article-title":"The kiss of (cell) death: Can venom-induced immune response contribute to dermal necrosis following arthropod envenomations?","volume":"57","author":"Dunbar","year":"2019","journal-title":"Clin. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0041-0101(83)90102-2","article-title":"Enzymatic and hemolytic properties of brown recluse spider (Loxosceles reclusa) toxin and extracts of venom apparatus, cephalothorax and abdomen","volume":"21","author":"Rekow","year":"1983","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.toxicon.2015.02.014","article-title":"Inflammation and oxidative stress in viper bite: An insight within and beyond","volume":"98","author":"Sunitha","year":"2015","journal-title":"Toxicon"},{"key":"ref_20","first-page":"903295","article-title":"Scorpion venom and the inflammatory response","volume":"2010","author":"Petricevichm","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/j.1553-2712.1996.tb03511.x","article-title":"Comparison of hyperbaric oxygen and dapsone therapy for Loxosceles envenomation","volume":"3","author":"Hobbs","year":"1996","journal-title":"Acad. Emerg. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1016\/j.jemermed.2009.08.055","article-title":"Suspected brown recluse envenomation: A case report and review of different treatment modalities","volume":"41","author":"Andersen","year":"2011","journal-title":"J. Emerg. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/01.ASW.0000504578.06579.20","article-title":"Nonhealing wounds caused by brown spider bites: Application of hyperbaric oxygen therapy","volume":"29","author":"Hadanny","year":"2016","journal-title":"Adv. Ski. Skin. Wound Care"},{"key":"ref_24","first-page":"4","article-title":"HBO2 in snake envenomation (atrox albinus rattlesnake): A case report in a human","volume":"43","author":"Zanon","year":"2016","journal-title":"Undersea Hyperb. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.22462\/3.4.2017.13","article-title":"Cave canem: HBO2 therapy efficacy on Capnocytophaga canimorsus infections: A case series","volume":"44","author":"Marmo","year":"2017","journal-title":"Undersea Hyperb. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e230000","DOI":"10.1136\/bcr-2019-230000","article-title":"Brown recluse (L. rufescens) can bite in Northern Italy, too: First case report and review of the literature","volume":"12","author":"Abbott","year":"2019","journal-title":"BMJ Case Rep"},{"key":"ref_27","first-page":"E88","article-title":"Report of cutaneous loxoscelism caused by violin spider bite in Northern Italy","volume":"61","author":"Starace","year":"2021","journal-title":"Int. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.toxicon.2004.07.012","article-title":"Brown Spiders and Loxoscelism","volume":"44","author":"Mangili","year":"2004","journal-title":"Toxicon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0140-6736(10)62230-1","article-title":"Spider Bite","volume":"378","author":"Isbister","year":"2021","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1007\/s00204-020-02719-0","article-title":"Clinical Aspects, Diagnosis and Management of Loxosceles Spider Envenomation: Literature and Case Review","volume":"94","author":"Lopes","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_31","first-page":"420","article-title":"Cutaneous and Visceral Loxoscelism: A Systematic Review","volume":"26","author":"Silva","year":"2009","journal-title":"Rev. Chil. Infectol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.toxicon.2021.01.004","article-title":"History, Challenges and Perspectives on Loxosceles (Brown Spiders) Antivenom Production in Brazil","volume":"192","author":"Miranda","year":"2021","journal-title":"Toxicon"},{"key":"ref_33","first-page":"199","article-title":"Treatment of clinically diagnosed brown recluse spider bites with hyperbaric oxygen: A clinical observation","volume":"83","author":"Svendsen","year":"1986","journal-title":"J. Ark. Med. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/0041-0101(91)90081-2","article-title":"Hyperbaric oxygen effects on brown reclus espider (Loxosceles reclusa) envenomation in rabbits","volume":"29","author":"Strain","year":"1991","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1553-2712.1997.tb03733.x","article-title":"Brown recluse spider envenomation: Is hyperbaric oxygen the answer? Hobbs GD","volume":"4","year":"1997","journal-title":"Acad Emerg Med."},{"key":"ref_36","unstructured":"Kindwall, E.P., and Whelan, H.T. (1999). Treatment of the brown recluse spider (Loxosceles reclusa) bite with hyperbaric oxygen Therapy. Hyperbaric Medicine Practice, Best Publishing Co."},{"key":"ref_37","first-page":"12783","article-title":"Oxy-inflammation in hyperbaric oxygen therapy applications","volume":"35","author":"Bosco","year":"2025","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41424-018-0031-6","article-title":"Oxidative stress as a biomarker for monitoring treated celiac disease","volume":"9","author":"Moretti","year":"2018","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mrakic-Sposta, S., Vezzoli, A., Garetto, G., Paganini, M., Camporesi, E., Giacon, T.A., Dellanoce, C., Agrimi, J., and Bosco, G. (2023). Hyperbaric Oxygen Therapy Counters Oxidative Stress\/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes. Metabolites, 13.","DOI":"10.3390\/metabo13101032"},{"key":"ref_40","first-page":"2","article-title":"Short-term suborbital space flight curtails astronauts\u2019 dopamine levels increasing cortisol\/BDNF and prompting pro-oxidative\/inflammatory milieu","volume":"12","author":"Bosco","year":"2025","journal-title":"Mil. Med. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Montorsi, M., Vezzoli, A., Mrakic Sposta, F., Gussoni, M., Brizzolari, A., Bosco, G., Dellanoce, C., Barassi, A., Picconi, B., and Ranuncoli, C. (2025). Systemic Responses Towards Oxy-Inflammation, Hormones, and Mood in Breast Cancer Survivors: Preliminary Evidences from Dragon Boat Endurance Race. J. Clin. Med., 14.","DOI":"10.3390\/jcm14072532"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.brs.2025.05.111","article-title":"Spinal tDCS on Oxy-Inflammation in patients with Multiple Sclerosis: A pilot study","volume":"18","author":"Ferrucci","year":"2025","journal-title":"Brain Stimul."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0304-3959(97)00005-5","article-title":"The visual analogue pain intensity scale: What is moderate pain in millimetres?","volume":"72","author":"Collins","year":"1997","journal-title":"Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1097\/00000658-198511000-00020","article-title":"Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision","volume":"202","author":"Rees","year":"1985","journal-title":"Ann. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4091278","DOI":"10.1155\/2019\/4091278","article-title":"Loxoscelism: Cutaneous and Hematologic Manifestations","volume":"2019","author":"Nguyen","year":"2019","journal-title":"Adv. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1093\/ckj\/sft111","article-title":"Clinicopathological course of acute kidney injury following brown recluse (Loxoscles reclusa) envenomation","volume":"6","author":"Anwar","year":"2013","journal-title":"Clin. Kidney J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molimm.2017.12.009","article-title":"Loxosceles venom Sphingomyelinase D activates human blood leukocytes: Role of the complement system","volume":"94","author":"Lopes","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lopes, P.H., van den Berg, C.W., and Tambourgi, D.V. (2020). Sphingomyelinases D From Loxosceles Spider Venoms and Cell Membranes: Action on Lipid Rafts and Activation of Endogenous Metalloproteinases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00636"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.toxicon.2007.08.011","article-title":"Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury","volume":"51","author":"Malaque","year":"2008","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1053\/j.ctsap.2006.10.004","article-title":"Brown spider envenomation","volume":"21","author":"Peterson","year":"2006","journal-title":"Clin. Tech. Small Anim. Pract."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1553-2712.1997.tb03738.x","article-title":"Brown recluse spider envenomation: A prospective trial of hyperbaric oxygen therapy","volume":"4","author":"Maynor","year":"1997","journal-title":"Acad. Emerg. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1007\/s00204-020-02830-2","article-title":"Cytotoxic and genotoxic effects on human keratinocytes triggered by sphingomyelinase D from Loxosceles venom","volume":"94","author":"Lopesm","year":"2020","journal-title":"Arch. Toxicol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:43Z","timestamp":1760033263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["metabo15070470"],"URL":"https:\/\/doi.org\/10.3390\/metabo15070470","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}