{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:23:15Z","timestamp":1790126595179,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jagiellonian University Medical College in Poland","award":["N41\/DBS\/001467"],"award-info":[{"award-number":["N41\/DBS\/001467"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adiponectin is adipokine exhibiting beneficial metabolic action through lipid and carbohydrate metabolism stimulation, as well as anti-inflammatory action. We have determined the role of adiponectin in gastroprotection against the formation of acute gastric lesions induced by ischemia\u2013reperfusion (I\/R). Gastric lesions evoked by I\/R are a serious clinical entity; however, the participation of reactive oxygen species (ROS) and lipid peroxidation products and the involvement of nitric oxide (NO), neuropeptides released from sensory afferent nerves, and the hormone gastrin in the potential gastroprotective action of adiponectin remains unknown. Therefore, we determined the interplay between capsaicin-sensitive afferent nerves, the NO\/NOS system, lipid peroxidation products, and the expression of pro-inflammatory and antioxidative factors in the gastroprotective action of adiponectin against gastric I\/R. injury. Wistar rats was administered with adiponectin in graded doses (1\u201340 \u03bcg\/kg i.v.) with or without: (a) blockade of nitric oxide (NO) activity by L-nitro-L-arginine (L-NNA) and (b) deactivation of sensory nerves by capsaicin (125 mg\/kg s.c. 10 days before experiment conduction). They were then exposed to 30 min of ischemia by clamping of the celiac artery followed by 3 h of reperfusion after clamp release. After 3 h, the rats were euthanized with pentobarbital and their gastric blood flow (GBF) was determined by laser Doppler flowmetry, their blood was withdrawn to assess plasma gastrin levels, and the area of gastric lesions was measured by planimetry. Gastric biopsy samples were excised to determine gastric mucosal levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). In separate groups of animals with chronic gastric fistula, the effect of adiponectin on gastric acid secretion was determined. Adiponectin dose-dependently reduced the gastric lesions induced by I\/R and this effect was accompanied by an increase in GBF. Blockade of NO-synthase with L-NNA (20 mg\/kg i.p.) reversed the protective effect and the rise in GBF induced by this adipokine, and both these effects were restored when L-arginine was added to L-NNA. Capsaicin denervation also impeded the beneficial action of adiponectin in rats, but these effects were in part restored when exogenous CGRP was combined with adiponectin. Adiponectin dose-dependently decreased gastric acid secretion, the expression of mRNA for pro-inflammatory cytokines, and MDA plus 4-HNE content, while significantly increasing SOD, GSH and plasma gastrin increments. We conclude that adiponectin exerts gastroprotection against I\/R-induced gastric lesions, through mechanisms involving NO and neuropeptides such as CGRP being released from sensory nerves, a decrease in lipid peroxidation (MDA+4-HNE), an increase of antioxidative factors (SOD, GSH), and the inhibition of gastric acid secretion.<\/jats:p>","DOI":"10.3390\/ijms27062827","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:49:28Z","timestamp":1774255768000},"page":"2827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gastroprotective Action of Adiponectin Against Gastric Mucosal Injury Induced by Ischemia and Reperfusion\u2014Involvement of Nitric Oxide, Sensory Afferent Nerves, and Anti-Inflammatory Mediators"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-8042","authenticated-orcid":false,"given":"S\u0142awomir","family":"Kwiecien","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-2002","authenticated-orcid":false,"given":"Aleksandra","family":"Szlachcic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-9617","authenticated-orcid":false,"given":"Dagmara","family":"Wojcik-Grzybek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-3329","authenticated-orcid":false,"given":"Zbigniew","family":"Sliwowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-2235","authenticated-orcid":false,"given":"Malgorzata","family":"Strzalka","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Szczyrk","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0294-5185","authenticated-orcid":false,"given":"Agata","family":"Ptak-Belowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-0065","authenticated-orcid":false,"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1097\/CCM.0b013e31821b85db","article-title":"Downregulation of adiponectin induced by tumor necrosis factor \u03b1 is involved in the aggravation of posttraumatic myocardial ischemia\/reperfusion injury","volume":"39","author":"Liu","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1089\/ars.2010.3722","article-title":"Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms","volume":"15","author":"Yi","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12328-016-0668-1","article-title":"Influence of metabolic syndrome on upper gastrointestinal disease","volume":"9","author":"Sogabe","year":"2016","journal-title":"Clin. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10620-016-4377-x","article-title":"Nitric oxide and hydrogen sulfide interact when modulating gastric physiological functions in rodents","volume":"62","author":"Lucetti","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_5","first-page":"717","article-title":"Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide\u2014Induced gastroprotection against stress ulcerogenesis","volume":"67","author":"Kwiecien","year":"2016","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_6","first-page":"515","article-title":"Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, interacts with gastric oxidative metabolism and enhances stress\u2014Induced gastric lesions","volume":"63","author":"Kwiecien","year":"2012","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9099","DOI":"10.3390\/molecules20059099","article-title":"Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing","volume":"20","author":"Magierowski","year":"2015","journal-title":"Molecules"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2337\/db14-0267","article-title":"Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin sensitivity during high-fat diet feeding in mice","volume":"64","author":"Liu","year":"2015","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1515\/hmbci-2013-0053","article-title":"The role of leptin\/adiponectin ratio in metabolic syndrome and diabetes","volume":"18","year":"2014","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Uraki, S., Tameda, M., Sugimoto, K., Shiraki, K., Takei, Y., Nobori, T., and Ito, M. (2015). Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2\/4 Signaling. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131346"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s11684-013-0283-1","article-title":"Adiponectin: Mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic post-conditioning","volume":"7","author":"Wang","year":"2013","journal-title":"Front. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.freeradbiomed.2013.05.043","article-title":"N-Acetylcysteine and allopurinol up-regulated the Jak\/STAT3 and PI3K\/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes","volume":"63","author":"Wang","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6437467","DOI":"10.1155\/2017\/6437467","article-title":"Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia\/Reperfusion Injury under Diabetes","volume":"2017","author":"Zhao","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ncpcardio1398","article-title":"Protective vascular and myocardial effects of adiponectin","volume":"6","author":"Goldstein","year":"2009","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_15","first-page":"252","article-title":"Protective effects of adiponectin on myocardial ischemia-reperfusion injury in rats","volume":"38","author":"Wang","year":"2010","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1161\/CIRCINTERVENTIONS.109.872044","article-title":"Impact of a single intracoronary administration of adiponectin on myocardial ischemia\/reperfusion injury in a pig model","volume":"3","author":"Kondo","year":"2010","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mazur-Bialy, A.I., Bilski, J., Wojcik, D., Brzozowski, B., Surmiak, M., Hubalewska\u2013Mazgaj, M., Chmura, A., Magierowski, M., Magierowska, K., and Mach, T. (2017). Beneficial effect of voluntary exercise on experimental colitis in mice fed a high\u2014Fat diet: The role of irisin, adiponectin and proinflammatory biomarkers. Nutrients, 9.","DOI":"10.3390\/nu9040410"},{"key":"ref_18","first-page":"243","article-title":"New insight into the direct anti-inflammatory activity of a myokine irisin against proinflammatory activation of adipocytes. Implication for exercise in obesity","volume":"68","author":"Bilski","year":"2017","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"786","DOI":"10.4158\/EP15963.OR","article-title":"ACTN3 Gene R577X Polymorphism associated with high-density lipoprotein cholesterol and adiponectin in rugby players","volume":"22","author":"Nirengi","year":"2016","journal-title":"Endocr. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.pharep.2016.04.009","article-title":"Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence","volume":"68","author":"Bilski","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"619649","DOI":"10.1155\/2014\/619649","article-title":"Serum levels of resistin, adiponectin, and apelin in gastroesophageal cancer patients","volume":"2014","author":"Diakowska","year":"2014","journal-title":"Dis. Markers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.7314\/APJCP.2014.15.11.4711","article-title":"Lack of any prognostic relationship between adiponectin receptor (Adipo R1\/R2) expression for early\/advanced stage gastric cancer","volume":"15","author":"Ayyildiz","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1515\/cclm-2013-0453","article-title":"PBMC expressed adiponectin mRNA is predictive of survival in patients with gastric cancer","volume":"51","author":"Tsai","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11033-014-3775-4","article-title":"Association of variants on ADIPOQ and AdipoR1 and the prognosis of gastric cancer patients after gastrectomy treatment","volume":"42","author":"Wu","year":"2015","journal-title":"Mol. Biol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1097\/MOG.0b013e328365d42e","article-title":"Gastroduodenal mucosal defense","volume":"29","author":"Kemmerly","year":"2013","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"G773","DOI":"10.1152\/ajpgi.00324.2011","article-title":"Protective role of adiponectin against ethanol\u2014Induced gastric injury in mice","volume":"302","author":"Yamamoto","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1093\/ajh\/hpu240","article-title":"Heme oxygenase improves renal function by potentiating podocyte-associated proteins in N\u03c9-Nitro-l-Arginine-Methyl Ester (l-NAME)-induced hypertension","volume":"28","author":"Ndisang","year":"2015","journal-title":"Am. J. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.2174\/1381612821666150803145508","article-title":"Role of the heme oxygenase-adiponectin-atrial natriuretic peptide axis in renal function","volume":"21","author":"Ndisang","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_29","first-page":"10358","article-title":"Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet","volume":"15","author":"Miczke","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_30","first-page":"870","article-title":"Effect of L-arginine supplementation on insulin resistance and adipocytokines levels in head and neck cancer non diabetic patients after surgery","volume":"30","author":"Izaola","year":"2014","journal-title":"Nutr. Hosp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1515\/folmed-2016-0039","article-title":"Pathophysiological role of adiponectin, leptin and asymmetric dimethylarginine in the process of atherosclerosis","volume":"58","author":"Koleva","year":"2016","journal-title":"Folia Medica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1007\/s00125-017-4259-6","article-title":"Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice","volume":"60","author":"Sakanashi","year":"2017","journal-title":"Diabetologia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/cvr\/cvn017","article-title":"Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide","volume":"78","author":"Gonon","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.physbeh.2015.06.016","article-title":"High fat diet induced changes in gastric vagal afferent response to adiponectin","volume":"152","author":"Kentish","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1093\/cvr\/cvx062","article-title":"Sensory innervation of perivascular adipose tissue: A crucial role in artery vasodilatation and leptin release","volume":"113","author":"Dunn","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13250","DOI":"10.3748\/wjg.v21.i47.13250","article-title":"Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury","volume":"21","author":"Liu","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E1436","DOI":"10.1152\/ajpendo.00445.2013","article-title":"Adiponectin inhibits oxidative\/nitrative stress during myocardial ischemia and reperfusion via PKA signaling","volume":"305","author":"Zhang","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0014-2999(00)00287-9","article-title":"Role of gastric acid secretion in progression of acute gastric erosions induced by ischemia\u2014Reperfusion into gastric ulcers","volume":"398","author":"Brzozowski","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.soard.2008.08.013","article-title":"Response of adiponectin and its receptors to changes in metabolic state after gastric bypass surgery: Dissociation between adipose tissue expression and circulating levels","volume":"5","author":"Savu","year":"2009","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.4049\/jimmunol.1401149","article-title":"Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation","volume":"193","author":"Varol","year":"2014","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000337591","article-title":"Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin","volume":"29","author":"Burgess","year":"2012","journal-title":"Cell Physiol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0024-3205(96)00500-0","article-title":"A new gastric ulcer model induced by ischemia-reperfusion in the rat: Role of leukocytes on ulceration in rat stomach","volume":"59","author":"Wada","year":"1996","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137122","DOI":"10.1016\/j.neulet.2023.137122","article-title":"Peripheral administration of neuropeptide W inhibits gastric emptying in rats: The role of small diameter afferent fibers and cholecystokinin receptors","volume":"800","author":"Tamer","year":"2023","journal-title":"Neurosci. Lett."},{"key":"ref_44","first-page":"261","article-title":"Role of curcumin in protection of gastric mucosa against stress-induced gastric mucosal damage. Involvement of hypoacidity, vasoactive mediators, and sensory neuropeptides","volume":"67","author":"Czekaj","year":"2016","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_45","first-page":"156","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2827\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:49:35Z","timestamp":1774255775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062827"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062827","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}