{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:27:00Z","timestamp":1779233220010,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Diabetes mellitus (DM) is associated with vascular complications that increase morbidity and mortality. Natural antioxidants play a vital role in reducing diabetes-related damage. This study investigated the protective effects of the phenolic monoterpene carvacrol (CAR) against diabetic complications. Thirty-two male Wistar Albino rats (4 months, 250\u2013300 g) were divided into four groups: control, DM, DM + DMSO, and DM + CAR. Type 1 diabetes was induced via intraperitoneal injection of 50 mg\/kg streptozotocin (STZ). The DM + CAR group received 20 mg\/kg CAR daily for four weeks. Body weight and blood glucose levels were regularly monitored. At the end of the study, aortic tissues were examined using hematoxylin\u2013eosin (H&amp;E), Verhoeff\u2013Van Gieson, and immunohistochemical staining, while cardiac tissues were analyzed with H&amp;E and Masson\u2019s trichrome. Serum levels of ischemia-modified albumin (IMA), cholesterol (CHOL), triglycerides (TG), and high-density lipoprotein (HDL) were measured. In the DM group, IMA and CHOL levels were increased (p = 0.0208 and p = 0.0207, respectively), apoptosis was elevated (caspase-3 expression, p = 0.0001), and marked tissue damage was observed. In contrast, in the DM + CAR group, IMA levels (p = 0.0228) and caspase-3 expression (p = 0.0457) were reduced, and notable improvements were detected in vascular and cardiac tissues. These results suggest that CAR protects against diabetic complications by modulating oxidative stress, inhibiting apoptosis, and preventing tissue injury.<\/jats:p>","DOI":"10.3390\/biom16030431","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:26:38Z","timestamp":1773393998000},"page":"431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Carvacrol on Aortic Damage in a Streptozotocin-Induced Type 1 Diabetic Rat Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-7062","authenticated-orcid":false,"given":"Seda","family":"Cetinkaya Karabekir","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Izmir Bak\u0131rcay University, Izmir 35665, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-8123","authenticated-orcid":false,"given":"Burcu","family":"Gultekin","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Necmettin Erbakan University, Meram, Konya 42090, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8759-4507","authenticated-orcid":false,"given":"Hasan Basri","family":"Savas","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Mardin Artuklu University, Mardin 47000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-5292","authenticated-orcid":false,"given":"Gokhan","family":"Cuce","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Necmettin Erbakan University, Meram, Konya 42090, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-9154","authenticated-orcid":false,"given":"Serpil","family":"Kalkan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Necmettin Erbakan University, Meram, Konya 42090, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.2337\/dc24-S002","article-title":"2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes\u20142024","volume":"47","author":"ElSayed","year":"2024","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17016","DOI":"10.1038\/nrdp.2017.16","article-title":"Type 1 diabetes mellitus","volume":"3","author":"Katsarou","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 diabetes","volume":"383","author":"Atkinson","year":"2014","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1001\/jama.2017.0686","article-title":"Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence with Complications During Teenage Years and Young Adulthood","volume":"317","author":"Dabelea","year":"2017","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1056\/NEJMoa1608664","article-title":"Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes","volume":"376","author":"Rawshani","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1093\/eurheartj\/ehv134","article-title":"Clinical diabetic cardiomyopathy: A two-faced disease with restrictive and dilated phenotypes","volume":"36","author":"Paulus","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.3906\/sag-1909-183","article-title":"Oxidative stress parameters in patients with ascending aortic dilatation","volume":"50","author":"Erdogan","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5594090","DOI":"10.1155\/2024\/5594090","article-title":"Therapeutic Effects of Nigella sativa Oil and Whole Seeds on STZ-Induced Diabetic Rats: A Biochemical and Immunohistochemical Study","volume":"2024","author":"AlSuhaymi","year":"2024","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s10616-013-9563-5","article-title":"Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats","volume":"66","author":"Bayramoglu","year":"2014","journal-title":"Cytotechnology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3892\/ijmm.2020.4654","article-title":"Carvacrol may alleviate vascular inflammation in diabetic db\/db mice","volume":"46","author":"Zhao","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e13899","DOI":"10.1111\/and.13899","article-title":"Protective effects of carvacrol against diabetes-induced reproductive damage in male rats: Modulation of Nrf2\/HO-1 signalling pathway and inhibition of Nf-kB-mediated testicular apoptosis and inflammation","volume":"53","author":"Arkali","year":"2021","journal-title":"Andrologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1113\/EP089235","article-title":"Effect of treatment with carvacrol and aerobic training on cardiovascular function in spontaneously hypertensive rats","volume":"106","author":"Costa","year":"2021","journal-title":"Exp. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.vph.2015.02.016","article-title":"Participation of the TRP channel in the cardiovascular effects induced by carvacrol in normotensive rat","volume":"67\u201369","author":"Dantas","year":"2015","journal-title":"Vasc. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jep.2009.08.020","article-title":"Cholesterol-reducer, antioxidant and liver protective effects of Thymbra spicata L. var. spicata","volume":"126","author":"Akkol","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","first-page":"460","article-title":"Effects of Nigella sativa L. seed oil on intima-media thickness and Bax and Caspase 3 expression in diabetic rat aorta","volume":"16","author":"Cuce","year":"2016","journal-title":"Anatol. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hou, N., Mai, Y., Qiu, X., Yuan, W., Li, Y., Luo, C., Liu, Y., Zhang, G., Zhao, G., and Luo, J.D. (2019). Carvacrol Attenuates Diabetic Cardiomyopathy by Modulating the PI3K\/AKT\/GLUT4 Pathway in Diabetic Mice. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00998"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109825","DOI":"10.1016\/j.biopha.2020.109825","article-title":"Carvacrol protects against diabetes-induced hypercontractility in the aorta through activation of the PI3K\/Akt pathway","volume":"125","author":"Liu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, Y., Mai, Y., Qiu, X., Chen, X., Li, C., Yuan, W., and Hou, N. (2020). Effect of long-term treatment of Carvacrol on glucose metabolism in Streptozotocin-induced diabetic mice. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-02937-0"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4314\/ahs.v21i2.30","article-title":"Streptozotocin-induced type 1 and 2 diabetes in rodents: A model for studying diabetic cardiac autonomic neuropathy","volume":"21","author":"Akinlade","year":"2021","journal-title":"Afr. Health Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/10520295.2019.1566571","article-title":"Effects of Nigella sativa oil on ovarian volume, oxidant systems, XIAP and NF-kB expression in an experimental model of diabetes","volume":"94","author":"Seflek","year":"2019","journal-title":"Biotech. Histochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/00365513.2017.1422540","article-title":"The significance of thiol\/disulfide homeostasis and ischemia-modified albumin levels to assess the oxidative stress in patients with different stages of diabetes mellitus","volume":"78","author":"Gulpamuk","year":"2018","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1080\/14767058.2018.1474871","article-title":"Role of ischemia-modified albumin in the evaluation of oxidative stress in intrahepatic cholestasis of pregnancy","volume":"32","author":"Tayyar","year":"2019","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1055\/s-0042-1757410","article-title":"Exploring the Novelty in Lipid Profiling of Patients: A Non-fasting Approach from Eastern India","volume":"15","author":"Saharia","year":"2023","journal-title":"J. Lab. Physicians"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Arun, D., Munir, W., Schmitt, L.V., Vyas, R., Ravindran, J.I., Bashir, M., Williams, I.M., Velayudhan, B., and Idhrees, M. (2021). Exploring the correlation and protective role of diabetes mellitus in aortic aneurysm disease. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.769343"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00395-020-00834-8","article-title":"Hyperglycemia regulates cardiac K(+) channels via O-GlcNAc-CaMKII and NOX2-ROS-PKC pathways","volume":"115","author":"Hegyi","year":"2020","journal-title":"Basic. Res. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s13300-019-0612-8","article-title":"Cardiovascular Risk in Type 1 Diabetes Mellitus","volume":"10","author":"Schofield","year":"2019","journal-title":"Diabetes Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Salvatore, T., Pafundi, P.C., Galiero, R., Albanese, G., Di Martino, A., Caturano, A., Vetrano, E., Rinaldi, L., and Sasso, F.C. (2021). The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms. Front. Med., 8.","DOI":"10.3389\/fmed.2021.695792"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/1753-0407.12011","article-title":"Role of nitric oxide and endothelin in endothelial maintenance of vasoconstrictor responses in aortas of diabetic female rats (\u4e00\u6c27\u5316\u6c2e\u4e0e\u5185\u76ae\u7d20\u5bf9\u7cd6\u5c3f\u75c5\u96cc\u6027\u5927\u9f20\u4e3b\u52a8\u8109\u8840\u7ba1\u5185\u76ae\u7ef4\u6301\u8840\u7ba1\u6536\u7f29\u53cd\u5e94\u7684\u5f71\u54cd)","volume":"5","author":"Sartoretto","year":"2013","journal-title":"J. Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1161\/CIRCULATIONAHA.107.710830","article-title":"Human apolipoprotein A-I gene transfer reduces the development of experimental diabetic cardiomyopathy","volume":"117","author":"Spillmann","year":"2008","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1161\/CIRCRESAHA.120.316738","article-title":"KLF5 Is Induced by FOXO1 and Causes Oxidative Stress and Diabetic Cardiomyopathy","volume":"128","author":"Kyriazis","year":"2021","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jarosz-Popek, J., Wolska, M., Gasecka, A., Czajka, P., Jakubik, D., Sharif, L., Adem, T., Liu, W.-L., Mirowska-Guzel, D., and Postula, M. (2020). The importance of non-coding RNAs in neurodegenerative processes of diabetes-related molecular pathways. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010009"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105948","DOI":"10.1016\/j.jsbmb.2021.105948","article-title":"Melatonin attenuates aortic oxidative stress injury and apoptosis in STZ-diabetes rats by Notch1\/Hes1 pathway","volume":"212","author":"Ren","year":"2021","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6018835","DOI":"10.1155\/2021\/6018835","article-title":"Comparison of the efficiency of Lepidium sativum, Ficus carica, and Punica granatum methanolic extracts in relieving hyperglycemia and hyperlipidemia of streptozotocin-induced diabetic rats","volume":"2021","author":"Ramadan","year":"2021","journal-title":"J. Diabetes Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100238","DOI":"10.1016\/j.metop.2023.100238","article-title":"Tapinanthus dodoneifolius leaf inhibits the activity of carbohydrate digesting enzymes and improves the insulin resistance induced in rats by dexamethasone","volume":"18","author":"Miaffo","year":"2023","journal-title":"Metab. Open"},{"key":"ref_36","first-page":"23","article-title":"Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats","volume":"50","author":"Budin","year":"2009","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"679","DOI":"10.5152\/akd.2014.5047","article-title":"Ameliorative effects of aminoguanidine on rat aorta in Streptozotocin-induced diabetes and evaluation of alpha-SMA expression","volume":"14","author":"Elbe","year":"2014","journal-title":"Anadolu Kardiyol. Derg."},{"key":"ref_38","first-page":"2115","article-title":"Effect of angiotensin II receptor-blocker (ARB) losartan on the myocardium of streptozotocin-induced diabetic rats: Histological and histochemical study","volume":"46","author":"Mansour","year":"2023","journal-title":"Egypt. J. Histol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s10735-024-10258-6","article-title":"Mathurameha ameliorates cardiovascular complications in high-fat diet\/low-dose streptozotocin-induced type 2 diabetic rats: Insights from histological and proteomic analysis","volume":"55","author":"Somsuan","year":"2024","journal-title":"J. Mol. Histol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/01480545.2018.1538233","article-title":"Safety and tolerability of carvacrol in healthy subjects: A phase I clinical study","volume":"44","author":"Ghorani","year":"2021","journal-title":"Drug Chem. Toxicol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/431\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:38:14Z","timestamp":1773394694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biom16030431"],"URL":"https:\/\/doi.org\/10.3390\/biom16030431","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]}}}