{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:15:30Z","timestamp":1774343730127,"version":"3.50.1"},"reference-count":64,"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":"National Key R&amp;D Program of China, Heilongjiang Provincial Funding for National Subjects","award":["2017YFD0502200, GX18B023"],"award-info":[{"award-number":["2017YFD0502200, GX18B023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>This study explored ultrastructural changes and the expression of oxidative stress-related genes and proteins in the laminar tissue of dairy cows with acute laminitis induced by oligofructose (OF) overload. Twelve clinically healthy, non-pregnant Chinese Holstein cows were randomly allocated into two groups: the OF-overload group (n = 6) and the control group (n = 6). 17 g\/kg BW of oligofructose (OF) dissolved in 20 mL\/kg BW of deionized water was provided to the OF-treated group, while the control group received 20 mL\/kg BW of deionized water via a stomach tube. Laminar tissue samples were collected at 72 h post-OF administration. RT-qPCR revealed significantly increased Keap1 mRNA expression (p = 0.0097) and significantly decreased Nrf2 (p &lt; 0.0001), Ho1 (p &lt; 0.0001), and Nqo1 (p = 0.0101) mRNA expression in the OF group compared to the control group. Western blot analysis confirmed corresponding protein-level changes, with significantly increased Keap1 (p = 0.0062) and significantly decreased Nrf2 (p = 0.0008), Ho1 (p = 0.0297), and Nqo1 (p = 0.0004) in the OF group compared with the control group. Immunohistochemical analysis revealed significantly increased cytoplasmic Keap1 distribution (p = 0.0200) and significantly decreased nuclear Nrf2 localization (p = 0.0032) in the OF group than the control group. Ultrastructural examination revealed significant pathological changes in the OF group, including a reduced number of hemidesmosomes (p &lt; 0.01), an increased distance from epidermal basal cells to the lamina densa (p &lt; 0.01), thickened and damaged lamina densa with disorganized collagen fibers, and deformed basal cell nuclei with reduced chromatin relative to the control group. In conclusion, these findings demonstrate that OF-induced acute laminitis is associated with significant dysregulation of the Keap1-Nrf2 antioxidant pathway and severe ultrastructural damage to the dermal\u2013epidermal interface, suggesting that oxidative stress contributes to laminar tissue injury in dairy cows.<\/jats:p>","DOI":"10.3390\/ani16060980","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Stress and Ultrastructural Changes in Laminar Tissue of Dairy Cows with Acute Laminitis Induced by Oligofructose Overload"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1109-0764","authenticated-orcid":false,"given":"Muhammad Abid","family":"Hayat","sequence":"first","affiliation":[{"name":"Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China"},{"name":"Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiafeng","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-7602","authenticated-orcid":false,"given":"Jiantao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-3328","authenticated-orcid":false,"given":"Hongbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tuniyazi, M., Tang, R., Hu, X., and Zhang, N. (2024). Methylated tirilazad may mitigate oligofructose-induced laminitis in horses. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1391892"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.rvsc.2023.06.001","article-title":"Systematic review of the relationship between rumen acidosis and laminitis in cattle","volume":"161","author":"Passos","year":"2023","journal-title":"Res. Vet. Sci."},{"key":"ref_3","first-page":"104","article-title":"Laminitis in cattle: A bibliometric analysis","volume":"1","year":"2024","journal-title":"Res. Pract. Vet. Anim. Sci."},{"key":"ref_4","first-page":"307","article-title":"Pathogenesis of laminitis in dairy cows","volume":"23","author":"Bojkovski","year":"2023","journal-title":"Vet. \u017dur. Republik. Srpsk."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/01652176.1991.9694302","article-title":"Bovine laminitis: Clinical aspects, pathology and pathogenesis with reference to acute equine laminitis","volume":"13","author":"Boosman","year":"1991","journal-title":"Vet. Q."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12735","DOI":"10.1038\/s41598-021-92163-6","article-title":"Association between alterations in plasma metabolome profiles and laminitis in intensively finished Holstein bulls in a randomized controlled study","volume":"11","author":"Scheu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3168\/jds.2009-2038","article-title":"Biomechanics and histology of bovine claw suspensory tissue in early acute laminitis","volume":"93","author":"Danscher","year":"2010","journal-title":"J. Dairy Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dong, S.W., Zhang, S.D., Wang, D.S., Wang, H., Shang, X.F., Yan, P., Yan, Z.T., and Yang, Z.Q. (2015). Comparative proteomics analysis provide novel insight into laminitis in Chinese Holstein cows. BMC Vet. Res., 11.","DOI":"10.1186\/s12917-015-0474-x"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tvjl.2018.07.002","article-title":"Use of statistical modelling to investigate the pathogenesis of claw horn disruption lesions in dairy cattle","volume":"238","author":"Randall","year":"2018","journal-title":"Vet. J."},{"key":"ref_10","unstructured":"Greenough, P.R. (2007). Bovine Laminitis and Lameness: A Hands on Approach, Saunders Ltd."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.3168\/jds.S0022-0302(04)73424-4","article-title":"Acute bovine laminitis: A new induction model using alimentary oligofructose overload","volume":"87","author":"Thoefner","year":"2004","journal-title":"J. Dairy Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3168\/jds.2008-1271","article-title":"Oligofructose overload induces lameness in cattle","volume":"92","author":"Danscher","year":"2009","journal-title":"J. Dairy Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.3168\/jds.S0022-0302(05)72957-X","article-title":"Histopathology of oligofructose-induced acute laminitis in heifers","volume":"88","author":"Thoefner","year":"2005","journal-title":"J. Dairy Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1590\/S0100-736X2013000500011","article-title":"Histopathology of dairy cows\u2019 hooves with signs of naturally acquired laminitis","volume":"33","author":"Mendes","year":"2013","journal-title":"Pesqui. Vet. Bras."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.2042-3306.2010.00122.x","article-title":"Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis","volume":"43","author":"Leise","year":"2011","journal-title":"Equine Vet. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jvim.15027","article-title":"Effect of continuous digital hypothermia on lamellar inflammatory signaling when applied at a clinically-relevant timepoint in the oligofructose laminitis model","volume":"32","author":"Dern","year":"2018","journal-title":"J. Vet. Int. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S1090-0233(03)00053-4","article-title":"The bovine digital cushion\u2014A descriptive anatomical study","volume":"167","author":"Raber","year":"2004","journal-title":"Vet. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/00480169.1992.35718","article-title":"\u201cSubclinical\u201d laminitis in dairy cattle","volume":"40","author":"Vermunt","year":"1992","journal-title":"N. Z. Vet. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00418-025-02397-y","article-title":"Distribution of endocannabinoid system receptors in the equine hoof: Dysregulation as a potential therapeutic target for laminitis","volume":"163","author":"Gobbo","year":"2025","journal-title":"Histochem. Cell Bio."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110935","DOI":"10.1016\/j.vetimm.2025.110935","article-title":"Enhanced apoptosis in damaged laminar tissue of acute laminitis induced by oligofructose overload in dairy cows","volume":"284","author":"Hayat","year":"2025","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108365","DOI":"10.1016\/j.mrrev.2021.108365","article-title":"Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer","volume":"787","author":"Caliri","year":"2021","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_22","first-page":"1","article-title":"Oxidative stress and antioxidants in health and disease","volume":"47","author":"Otlu","year":"2023","journal-title":"J. Lab. Med."},{"key":"ref_23","first-page":"657","article-title":"Determination of dynamic thiol-disulfide levels in dairy cattle with foot disease Dinami\u010dke razine tiol-disulfida u mlije\u010dnih goveda s bolestima papaka","volume":"92","author":"Erdal","year":"2022","journal-title":"Vet. Arhiv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.joca.2009.08.015","article-title":"Inhibition of cyclooxygenase-2 expression and prostaglandin E2 production in chondrocytes by avocado soybean unsaponifiables and epigallocatechin gallate","volume":"18","author":"Heinecke","year":"2010","journal-title":"Osteoarthritis Cartilage."},{"key":"ref_25","first-page":"289","article-title":"Determination of the activity of selected antioxidant enzymes during bovine laminitis, induced by oligofructose overload","volume":"76","author":"Hayat","year":"2020","journal-title":"Med. Weter."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s12011-014-0207-1","article-title":"Oxidative stress and imbalance of mineral metabolism contribute to lameness in dairy cows","volume":"164","author":"Zhao","year":"2015","journal-title":"Bio. Trace Elem. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, S., Ding, J., Jiang, L., Hayat, M.A., Song, Q., Li, Y., Zhang, X., and Zhang, J. (2020). Dynamic ROS production and gene expression of heifers blood neutrophil in a oligofructose overload model. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00211"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hong, Y., Boiti, A., Vallone, D., and Foulkes, N.S. (2024). Reactive oxygen species signaling and oxidative stress: Transcriptional regulation and evolution. Antioxidants, 13.","DOI":"10.3390\/antiox13030312"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102389","DOI":"10.1016\/j.redox.2022.102389","article-title":"Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway","volume":"54","author":"Liu","year":"2022","journal-title":"Redox Bio."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cui, L., Duan, J., Mao, P., Zhong, J., He, S., Dong, J., Liu, K., Guo, L., Li, J., and Wang, H. (2025). Meloxicam alleviates oxidative stress through Nrf2\/HO-1 activation in bovine endometrial epithelial cells. Vet. Sci., 12.","DOI":"10.3390\/vetsci12060579"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"105853","DOI":"10.1016\/j.phrs.2021.105853","article-title":"The pivotal role of Nrf2 activators in adipocyte biology","volume":"173","author":"Jayasuriya","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Khan, M.Z., Li, L., Zhan, Y., Binjiang, H., Liu, X., Kou, X., Khan, A., Qadeer, A., Ullah, Q., and Alzahrani, K.J. (2025). Targeting Nrf2\/KEAP1 signaling pathway using bioactive compounds to combat mastitis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1425901"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.vetimm.2008.11.016","article-title":"Tissue concentrations of 4-HNE in the black walnut extract model of laminitis: Indication of oxidant stress in affected laminae","volume":"129","author":"Yin","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"48","DOI":"10.2746\/042516406X151320","article-title":"Laminar xanthine oxidase, superoxide dismutase and catalase activities in the prodromal stage of black-walnut induced equine laminitis","volume":"39","author":"Loftus","year":"2007","journal-title":"Equine Vet. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/S0093-691X(97)00098-8","article-title":"A lameness scoring system that uses posture and gait to predict dairy cattle reproductive performance","volume":"47","author":"Sprecher","year":"1997","journal-title":"Theriogenol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3168\/jds.S0022-0302(89)79081-0","article-title":"A body condition scoring chart for Holstein dairy cows","volume":"72","author":"Edmonson","year":"1989","journal-title":"J. Dairy Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ding, J., Li, S., Jiang, L., Li, Y., Zhang, X., Song, Q., Hayat, M.A., Zhang, J.T., and Wang, H. (2020). Laminar inflammation responses in the oligofructose overload induced model of bovine laminitis. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00351"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hayat, M.A., Ding, J., Zhang, X., Liu, T., Zhang, J., Bokhari, S.G., Akbar, H., and Wang, H. (2023). Enhanced Autophagy in Damaged Laminar Tissue of Acute Laminitis Induced by Oligofructose Overloading in Dairy Cows. Animals, 13.","DOI":"10.20944\/preprints202306.1877.v1"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kim, M.J., and Jeon, J.H. (2022). Recent advances in understanding Nrf2 agonism and its potential clinical application to metabolic and inflammatory diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052846"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105490","DOI":"10.1016\/j.neuint.2023.105490","article-title":"Oxidative stress, inflammation and hormesis: The role of dietary and lifestyle modifications on aging","volume":"164","author":"Sharma","year":"2023","journal-title":"Neurochem. Int."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tkaczenko, H., and Kurhaluk, N. (2025). Antioxidant-rich functional foods and exercise: Unlocking metabolic health through Nrf2 and related pathways. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031098"},{"key":"ref_42","first-page":"18e37326","article-title":"The role of Keap1-Nrf2 signaling pathway in the treatment of respiratory diseases and the research progress on targeted drugs","volume":"10","author":"Zhang","year":"2024","journal-title":"Heliyon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/med.21925","article-title":"KEAP1-NRF2 protein\u2013protein interaction inhibitors: Design, pharmacological properties and therapeutic potential","volume":"43","author":"Crisman","year":"2023","journal-title":"Med. Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1365-2443.2008.01234.x","article-title":"Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice","volume":"13","author":"Yoh","year":"2008","journal-title":"Genes Cells"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1046\/j.1523-1755.2001.00939.x","article-title":"Nrf2-deficient female mice develop lupus-like autoimmune nephritis","volume":"60","author":"Yoh","year":"2001","journal-title":"Kidney Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3168\/jds.2016-10871","article-title":"Lipopolysaccharide derived from the digestive tract provokes oxidative stress in the liver of dairy cows fed a high-grain diet","volume":"100","author":"Abaker","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.3168\/jds.2012-5967","article-title":"Expression of target genes of nuclear factor E2-related factor 2 in the liver of dairy cows in the transition period and at different stages of lactation","volume":"96","author":"Gessner","year":"2013","journal-title":"J. Dairy Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/evj.13933","article-title":"A review of cellular and molecular mechanisms in endocrinopathic, sepsis-related and supporting limb equine laminitis","volume":"55","author":"Elliott","year":"2023","journal-title":"Equine Vet. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0955-0674(96)80106-2","article-title":"Hemidesmosomes: Roles in adhesion, signaling and human diseases","volume":"8","author":"Borradori","year":"1996","journal-title":"Curr. Opin. Cell Bio."},{"key":"ref_50","first-page":"9","article-title":"The desmosome and hemidesmosome in cutaneous autoimmunity","volume":"107","author":"Lin","year":"1997","journal-title":"Clin. Exp. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"230","DOI":"10.2746\/0425164044877125","article-title":"Equine laminitis: Loss of hemidesmosomes in hoof secondary epidermal lamellae correlates to dose in an oligofructose induction model: An ultrastructural study","volume":"36","author":"French","year":"2004","journal-title":"Equine Vet. J."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wang, L., Pawlak, E.A., Johnson, P.J., Belknap, J.K., Eades, S., Stack, S., Cousin, H., and Black, S.J. (2013). Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056025"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2746\/0425164044877170","article-title":"Equine laminitis: Glucose deprivation and MMP activation induce dermo-epidermal separation in vitro","volume":"36","author":"French","year":"2004","journal-title":"Equine Vet. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2746\/0425164044877242","article-title":"Equine laminitis: Increased transcription of matrix metalloproteinase-2 (MMP-2) occurs during the developmental phase","volume":"36","author":"Pollitt","year":"2004","journal-title":"Equine Vet. J."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Johnson, P.J. (2017). Endocrine and metabolic dysregulation in laminitis: Role of corticosteroids. Equine Laminitis, Wiley.","DOI":"10.1002\/9781119169239.ch17"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.2042-3306.1998.tb05132.x","article-title":"Decreased glucose metabolism causes separation of hoof lamellae in vitro: A trigger for laminitis?","volume":"30","author":"Pass","year":"1998","journal-title":"Equine Vet. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1126\/science.277.5323.225","article-title":"Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5","volume":"277","author":"Giannelli","year":"1997","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/jvim.12252","article-title":"Expression and activity of collagenases in the digital laminae of horses with carbohydrate overload-induced acute laminitis","volume":"28","author":"Wang","year":"2014","journal-title":"J. Vet. Int. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.vetimm.2008.11.003","article-title":"Leukocyte-derived and endogenous matrix metalloproteinases in the lamellae of horses with naturally acquired and experimentally induced laminitis","volume":"129","author":"Loftus","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tvjl.2008.09.022","article-title":"Matrix metalloproteinases in inflammatory pathologies of the horse","volume":"183","author":"Clutterbuck","year":"2010","journal-title":"Vet. J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ding, J., Shi, M., Wang, L., Qi, D., Tao, Z., Hayat, M.A., Liu, T., Zhang, J.T., and Wang, H. (2020). Gene expression of metalloproteinases and endogenous inhibitors in the lamellae of dairy heifers with oligofructose-induced laminitis. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.597827"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.domaniend.2019.04.004","article-title":"Ultrastructural examination of basement membrane pathology in horses with insulin-induced laminitis","volume":"69","author":"Laat","year":"2019","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Khan, M.Z., Li, S., Ullah, A., Li, Y., Abohashrh, M., Alzahrani, F.M., Alzahrani, K.J., Alsharif, K.F., Wang, C., and Ma, Q. (2025). Therapeutic Agents Targeting the Nrf2 Signaling Pathway to Combat Oxidative Stress and Intestinal Inflammation in Veterinary and Translational Medicine. Vet. Sci., 13.","DOI":"10.3390\/vetsci13010025"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Thiruvengadam, M., Venkidasamy, B., Subramanian, U., Samynathan, R., Ali Shariati, M., Rebezov, M., Girish, S., Thangavel, S., Dhanapal, A.R., and Fedoseeva, N. (2021). Bioactive compounds in oxidative stress-mediated diseases: Targeting the NRF2\/ARE signaling pathway and epigenetic regulation. Antioxidant, 10.","DOI":"10.3390\/antiox10121859"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/6\/980\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:43:37Z","timestamp":1774331017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/6\/980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":64,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ani16060980"],"URL":"https:\/\/doi.org\/10.3390\/ani16060980","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}