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Thiamine pyrophosphate (TPP) has a role in reducing oxidative stress as well as acting as a coenzyme in enzymatic reactions. The aim of this study was to investigate the protective effect of TPP on the damage caused by indomethacin (IND), one of the NSAID group drugs, in the small intestine. In the experiment in which 32 rats were used, four groups were formed randomly (groups 1, 2, 3, 4; control, TPP, IND, IND\u2009+\u2009TPP group, respectively). Small intestinal injury was induced in group 3 and group 4 rats that were fasted 1\u00a0day beforehand by a single intragastric administration of 25\u00a0mg\/kg IND. Half an hour before the model was created, 20\u00a0mg\/kg TPP was administered to group 2 and group 4 by intragastric as pretreatment. Tissue changes, proinflammatory cytokines, oxidative stress status, macroscopic appearance, and histopathologic analysis were evaluated. All data were statistically analyzed, and significance was determined (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Prophylactic treatment with TPP resulted in maintenance of antioxidant enzymes (GPX, SOD) and GSH levels in small intestinal tissue analysis. However, the excessive increase in IND-induced lipid peroxidation (MDA) and total oxidant level (TOS) was not downregulated by TPP compared to group 3. Additionally, the treatment had no prophylactic effect on the reduction of proinflammatory cytokine (TNF-\u03b1, IL-6) levels in tissue. Histopathologic examination of the tissue revealed that IND disrupted the intestinal villus structure, causing erosive ulceration, degeneration, and inflammation. TPP reduced the inflamed areas and total tissue damage score in the IND group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In this study, the positive effects of TPP use on some parameters in a short period of time suggested that TPP may produce more significant results with changes in the time and dose of use. Indeed, these beneficial effects obtained with a single dose suggest that TPP may provide protection in small intestinal enteropathy as an antioxidant and anti-inflammatory agent.<\/jats:p>","DOI":"10.1007\/s00210-025-04213-9","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T04:51:50Z","timestamp":1745902310000},"page":"14441-14450","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thiamine pyrophosphate may protect indomethacin-induced small intestinal enteropathy in rats by inhibiting intestinal inflammation and oxidative stress"],"prefix":"10.1007","volume":"398","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4448-5129","authenticated-orcid":false,"given":"Seyda","family":"Secgin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4356-7449","authenticated-orcid":false,"given":"Mudassar","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2448-2910","authenticated-orcid":false,"given":"Mukhammadiy","family":"Khakimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-0811","authenticated-orcid":false,"given":"Hikmet","family":"Keles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-8528","authenticated-orcid":false,"given":"Tahir","family":"Kahraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"4213_CR1","doi-asserted-by":"publisher","unstructured":"Abd-Ellatif HR, Kamel GA, Ali AA (2025) Protective effects of infliximab on indomethacin-induced gastric ulcer in rats: the role of MAPK\/NF-KB p65 signaling pathway. 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