{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:51:31Z","timestamp":1767178291392,"version":"build-2238731810"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The present study aimed to investigate the efficacy of different doses of Eucerin-based ointment containing opium compared to routine treatment on experimentally induced burn injury. Male Wistar rats were divided into five experimental groups for topical application: silver sulfadiazine 1% (SSD), Eucerin-based ointment containing opium at concentrations of 0.05%, 0.5%, and 5%, and a Eucerin-based ointment containing 0.05% opium plus SSD (mixed group), following burn wound induction using the comb burn model. An equal volume of different ointments was administered topically. The wound appearances of different groups were photographed at different time points for 21 days. In addition, blood and skin samples were taken 2 and 10 days after thermal injury to assess inflammatory parameters and oxidative stress markers. Also, the liver enzyme activity and kidney function tests were assessed on day 10. The body weight in Opium 5% significantly decreased compared to all other groups after ten days. The wound area was significantly reduced (P&lt;0.05) in three groups: Opium 0.05%, Opium 0.5%, and mixed, compared to the SSD group on days 14 and 21. On day 21, the wound size in the Opium 5% group was significantly larger than that in the SSD group. Significantly lower serum levels of MDA were observed in all groups compared to the SSD group on days 2 and 10. There were no significant differences between treatment groups for concentrations of TNF-\u03b1 in serum and burned skin samples (p&gt;0.05). The serum concentrations of interleukin-10 in the mixed group were significantly higher compared to the SSD group on day 10. After ten days, groups were not different regarding AST, ALT, and creatinine concentrations (p&gt;0.05). Histopathological analysis revealed that the wound healing efficacy of opium at its lowest concentration (0.05%) surpassed that of silver sulfadiazine (SSD). Furthermore, the combination of 0.05% opium with SSD enhanced the wound repair potential of SSD in burn injuries. This study showed that opium ointment delayed wound closure dose-dependently. Low doses of topical opium ointment and its mixed application with silver sulfadiazine had a protective role in thermal-induced injury.<\/jats:p>","DOI":"10.1371\/journal.pone.0313659","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T13:26:39Z","timestamp":1732281999000},"page":"e0313659","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-analgesic effects of opioids: Topical application of Eucerin-based ointment containing opium on the healing process of thermal skin damage in rats"],"prefix":"10.1371","volume":"19","author":[{"given":"Omid","family":"Mehrpour","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khadijeh","family":"Farrokhfall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kobra","family":"Naseri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-6799","authenticated-orcid":true,"given":"Samaneh","family":"Nakhaee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"issue":"5","key":"pone.0313659.ref001","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s13346-017-0405-4","article-title":"Evaluation of propylene glycol nanoliposomes containing curcumin on burn wound model in rat: biocompatibility, wound healing, and anti-bacterial effects","volume":"7","author":"N Kianvash","year":"2017","journal-title":"Drug delivery and translational research"},{"issue":"2","key":"pone.0313659.ref002","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000321201","article-title":"Effect of opium dependency on burn healing in a rat model: an experimental study","volume":"20","author":"H Zeinalinejad","year":"2011","journal-title":"Medical Principles and Practice"},{"issue":"8","key":"pone.0313659.ref003","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/j.burns.2017.04.021","article-title":"Methylene blue reduces progression of burn and increases skin survival in an experimental rat model","volume":"43","author":"MJ Rosique","year":"2017","journal-title":"Burns"},{"issue":"5","key":"pone.0313659.ref004","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3390\/cosmetics9050093","article-title":"Enhanced Antimicrobial Activity of Silver Sulfadiazine Cosmetotherapeutic Nanolotion for Burn Infections","volume":"9","author":"Q-ua Fatima","year":"2022","journal-title":"Cosmetics"},{"key":"pone.0313659.ref005","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1590\/abd1806-4841.20198321","article-title":"Tissue healing efficacy in burn patients treated with 1% silver sulfadiazine versus other treatments: a systematic review and meta-analysis of randomized controlled trials","volume":"94","author":"ABdS Maciel","year":"2019","journal-title":"Anais brasileiros de dermatologia"},{"issue":"2","key":"pone.0313659.ref006","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.burns.2018.05.014","article-title":"Comparative study of Silver Sulfadiazine with other materials for healing and infection prevention in burns: A systematic review and meta-analysis","volume":"45","author":"HH Nimia","year":"2019","journal-title":"Burns"},{"issue":"3","key":"pone.0313659.ref007","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1742-481X.2012.00990.x","article-title":"Effect of opium dependency on secondary intention wound healing in a rat model: an experimental study","volume":"10","author":"J Vahedian","year":"2013","journal-title":"International Wound Journal"},{"key":"pone.0313659.ref008","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.trsl.2017.05.003","article-title":"Opioids and opioid receptors orchestrate wound repair","volume":"185","author":"Y Wang","year":"2017","journal-title":"Translational Research"},{"issue":"4","key":"pone.0313659.ref009","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1432-0436.2006.00065.x","article-title":"Deletion of \u03b4-opioid receptor in mice alters skin differentiation and delays wound healing","volume":"74","author":"M Bigliardi-Qi","year":"2006","journal-title":"Differentiation"},{"issue":"2","key":"pone.0313659.ref010","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/bph.12687","article-title":"Activation of the \u03b4\u2010opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration","volume":"172","author":"P Bigliardi","year":"2015","journal-title":"British journal of pharmacology"},{"issue":"1\u20134","key":"pone.0313659.ref011","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1081\/RRS-120014595","article-title":"Specific stimulation of migration of human keratinocytes by \u03bc-opiate receptor agonists","volume":"22","author":"PL Bigliardi","year":"2002","journal-title":"Journal of Receptors and Signal Transduction"},{"issue":"7","key":"pone.0313659.ref012","first-page":"89","article-title":"Opioid activity of peptides and wound healing of the skin","volume":"104","author":"V Vinogradov","year":"1987","journal-title":"Biulleten\u2019Eksperimental\u2019noi Biologii i Meditsiny"},{"issue":"37","key":"pone.0313659.ref013","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.2174\/138161212803582513","article-title":"Non-analgesic effects of opioids: peripheral opioid effects on inflammation and wound healing","volume":"18","author":"C Stein","year":"2012","journal-title":"Current pharmaceutical design"},{"key":"pone.0313659.ref014","first-page":"459","volume-title":"Textbook of Contact Dermatitis","author":"AC DE GROOT","year":"2013"},{"key":"pone.0313659.ref015","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.sbspro.2013.06.427","article-title":"New Trends in Brand Strategies","volume":"81","author":"B-M Amalancei","year":"2013","journal-title":"Procedia-Social and Behavioral Sciences"},{"key":"pone.0313659.ref016","first-page":"325","volume-title":"Lanolins. In Dry Skin and Moisturizers","author":"I Harris","year":"2005","edition":"2"},{"issue":"6","key":"pone.0313659.ref017","first-page":"437","article-title":"Eucerin: A Revolutionary Formulation Still Going Strong for Over a Century","volume":"14","author":"Y Anwar","year":"2016","journal-title":"Skinmed"},{"key":"pone.0313659.ref018","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jss.2020.11.068","article-title":"Modeling burn progression using comb burns: the impact of thermal contact duration on model outcomes","volume":"260","author":"RD Smith","year":"2021","journal-title":"Journal of Surgical Research"},{"key":"pone.0313659.ref019","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jff.2018.11.038","article-title":"Cinnamaldehyde has beneficial effects against oxidative stress and nitric oxide metabolites in the brain of aged rats fed with long-term, high-fat diet","volume":"52","author":"Z Ataie","year":"2019","journal-title":"Journal of Functional Foods"},{"key":"pone.0313659.ref020","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jff.2014.07.014","article-title":"Improved islet function is associated with anti-inflammatory, antioxidant and hypoglycemic potential of cinnamaldehyde on metabolic syndrome induced by high tail fat in rats","volume":"10","author":"K Farrokhfall","year":"2014","journal-title":"journal of functional foods"},{"issue":"2","key":"pone.0313659.ref021","first-page":"115","article-title":"Comparison of inducible nitric oxide synthase activity in pancreatic islets of young and aged rats","volume":"18","author":"K Farrokhfall","year":"2015","journal-title":"Iranian journal of basic medical sciences"},{"issue":"1","key":"pone.0313659.ref022","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0003-2697(78)90342-1","article-title":"Determination of malonaldehyde precursor in tissues by thiobarbituric acid test","volume":"86","author":"M Uchiyama","year":"1978","journal-title":"Analytical biochemistry"},{"issue":"3","key":"pone.0313659.ref023","first-page":"211","article-title":"L-arginine and Alzheimer\u2019s disease","volume":"2","author":"J Yi","year":"2009","journal-title":"International journal of clinical and experimental pathology"},{"issue":"2","key":"pone.0313659.ref024","doi-asserted-by":"crossref","first-page":"182","DOI":"10.11613\/BM.2011.028","article-title":"Validation of methods performance for routine biochemistry analytes at Cobas 6000 analyzer series module c501","volume":"21","author":"V Supak Smolcic","year":"2011","journal-title":"Biochemia Medica"},{"issue":"5","key":"pone.0313659.ref025","first-page":"218","article-title":"A new histological score grade for deep partial-thickness burn wound healing process","volume":"10","author":"H-F Guo","year":"2020","journal-title":"International journal of burns and trauma"},{"issue":"2","key":"pone.0313659.ref026","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1067-1927.2005.130207.x","article-title":"Opioids heal ischemic wounds in the rat","volume":"13","author":"T Poonawala","year":"2005","journal-title":"Wound Repair and Regeneration"},{"issue":"10","key":"pone.0313659.ref027","first-page":"487","article-title":"Effects of opioid peptide dalargin on reparative processes in wound healing","volume":"106","author":"A Shekhter","year":"1988","journal-title":"Biulleten\u2019Eksperimental\u2019noi Biologii i Meditsiny"},{"issue":"2","key":"pone.0313659.ref028","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1213\/ane.0b013e31817e6719","article-title":"Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice","volume":"107","author":"C-F Lam","year":"2008","journal-title":"Anesthesia & Analgesia"},{"issue":"1","key":"pone.0313659.ref029","first-page":"130","article-title":"Temporal effects of topical morphine application on cutaneous wound healing","volume":"109","author":"JM Rook","year":"2008","journal-title":"The Journal of the American Society of Anesthesiologists"},{"issue":"1","key":"pone.0313659.ref030","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jbiotec.2010.01.001","article-title":"3D-wound healing model: influence of morphine and solid lipid nanoparticles","volume":"148","author":"S K\u00fcchler","year":"2010","journal-title":"Journal of biotechnology"},{"issue":"3","key":"pone.0313659.ref031","first-page":"193","article-title":"Evaluation of wound healing and post-operative intra-abdominal adhesions in opium addicted rats","volume":"19","author":"MR Lashkarizadeh","year":"2015","journal-title":"Physiology and Pharmacology"},{"issue":"4","key":"pone.0313659.ref032","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1211\/jpp.61.04.0011","article-title":"Morphine or its withdrawal affects plasma malondialdehyde, vitamin E levels and absence or presence of abstinence signs in rats","volume":"61","author":"A Pinelli","year":"2009","journal-title":"Journal of Pharmacy and Pharmacology"},{"issue":"5","key":"pone.0313659.ref033","first-page":"1449","article-title":"Effect of long-term treatment of morphine on enzymes, oxidative stress indices and antioxidant status in male rat liver","volume":"7","author":"S Samarghandian","year":"2014","journal-title":"International journal of clinical and experimental medicine"},{"key":"pone.0313659.ref034","first-page":"34","article-title":"Oxidant\/antioxidant equilibrium in rats supplemented with diesel fuel or with opium poppy (Papaver somniferum L.) seed oil biodiesel","volume":"164","author":"L. Aksoy","year":"2013","journal-title":"Revue De Medecine Veterinaire"},{"issue":"2","key":"pone.0313659.ref035","first-page":"21","article-title":"Biochemical factors, MDA levels and Antioxidant activity in Opium addicted Hamsters","volume":"3","author":"Hemen Moradi Sardareh","year":"2014","journal-title":"International Research Journal of Biological Sciences"},{"issue":"3","key":"pone.0313659.ref036","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/1874467210666170919161045","article-title":"Socialization Alleviates Burden of Oxidative-Stress in Hippocampus and Prefrontal Cortex in Morphine Addiction Period in Male Rats","volume":"11","author":"H Famitafreshi","year":"2018","journal-title":"Current molecular pharmacology"},{"issue":"1","key":"pone.0313659.ref037","first-page":"38","article-title":"Induction of liver oxidative damage and monocyte chemoattractant protein-1 in opium addicted male rats","volume":"5","author":"GQ Othman","year":"2015","journal-title":"Polytechnic"},{"key":"pone.0313659.ref038","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bbr.2013.02.034","article-title":"Role of oxidative stress and inducible nitric oxide synthase in morphine-induced tolerance and dependence in mice. Effect of alpha-lipoic acid","volume":"247","author":"AO Abdel-Zaher","year":"2013","journal-title":"Behavioural brain research"},{"issue":"10","key":"pone.0313659.ref039","first-page":"616","article-title":"Study of Serum Malondialdehyde Level in Opioid and Methamphetamine Dependent Patients","volume":"55","author":"K Najafi","year":"2017","journal-title":"Acta Medica Iranica"},{"issue":"2","key":"pone.0313659.ref040","first-page":"72","article-title":"A study of plasma lipid peroxidation, lipids and blood sugar level in opium addicts compared with control group","volume":"1","author":"S Asgari","year":"2005","journal-title":"ARYA Journal"},{"issue":"15","key":"pone.0313659.ref041","doi-asserted-by":"crossref","first-page":"9110","DOI":"10.3390\/ijerph19159110","article-title":"A Pilot Study on the Association of Lead, 8-Hydroxyguanine, and Malondialdehyde Levels in Opium Addicts\u2019 Blood Serum with Illicit Drug Use and Non-Addict Persons","volume":"19","author":"FA Hesaruiyeh","year":"2022","journal-title":"International Journal of Environmental Research and Public Health"},{"key":"pone.0313659.ref042","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.npbr.2020.05.005","article-title":"Opium consumption exerts protective effect against cerebral ischemia through reducing inflammation and enhancing antioxidant defense in male rats","volume":"37","author":"S Yarahmadzehi","year":"2020","journal-title":"Neurology, Psychiatry and Brain Research"},{"issue":"5","key":"pone.0313659.ref043","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1590\/1414-431X20143697","article-title":"Therapeutic concentration of morphine reduces oxidative stress in glioma cell line","volume":"47","author":"MB Almeida","year":"2014","journal-title":"Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas"},{"issue":"2\u20133","key":"pone.0313659.ref044","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0014-2999(02)02922-9","article-title":"Morphine as a drug for stress ulcer prevention and healing in the stomach","volume":"460","author":"CH Cho","year":"2003","journal-title":"European journal of pharmacology"},{"key":"pone.0313659.ref045","doi-asserted-by":"crossref","DOI":"10.1007\/s10753-021-01566-0","article-title":"Association of miR-155, miR-187 and Inflammatory Cytokines IL-6, IL-10 and TNF-\u03b1 in Chronic Opium Abusers","volume":"45","author":"P Purohit","year":"2022","journal-title":"Inflammation"},{"key":"pone.0313659.ref046","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1743-7075-7-26","article-title":"Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007)","volume":"7","author":"A Esteghamati","year":"2010","journal-title":"Nutrition & metabolism"},{"issue":"7","key":"pone.0313659.ref047","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1038\/sj.jid.5701232","article-title":"IL-10 Overexpression Decreases Inflammatory Mediators and Promotes Regenerative Healing in an Adult Model of Scar Formation","volume":"128","author":"WH Peranteau","year":"2008","journal-title":"Journal of Investigative Dermatology"},{"issue":"5","key":"pone.0313659.ref048","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41577-022-00792-3","article-title":"Death by TNF: a road to inflammation","volume":"23","author":"G van Loo","year":"2023","journal-title":"Nature Reviews Immunology"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0330173","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T13:26:54Z","timestamp":1732282014000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313659"}},"subtitle":[],"editor":[{"given":"Kamal Ahmad","family":"Qureshi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,22]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0313659","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,22]]}}}