{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:48Z","timestamp":1785431448474,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004202","name":"Ondokuz Mayis University","doi-asserted-by":"crossref","award":["PYO.VET.1904.20.011"],"award-info":[{"award-number":["PYO.VET.1904.20.011"]}],"id":[{"id":"10.13039\/501100004202","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PYO.VET.1904.20.011"],"award-info":[{"award-number":["PYO.VET.1904.20.011"]}],"id":[{"id":"https:\/\/ror.org\/028k5qw24","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion or action. Persistent hyperglycemia contributes to the development of micro- and macrovascular complications, particularly affecting the kidneys and leading to diabetic nephropathy through mechanisms involving oxidative stress, fibrosis and apoptosis. Purpose: This study aimed to investigate the protective effects of hesperidin and carvacrol, individually and in combination, on streptozotocin-induced diabetic nephropathy in a Type 1 diabetes rat model. Study design: An experimental in vivo animal study was conducted using a streptozotocin-induced Type 1 diabetic rat model. Methods: Sixty adult Wistar Albino rats were randomly divided into six groups (n = 10): Control, Diabetes, Vehicle, Diabetes + Carvacrol, Diabetes + Hesperidin, and Diabetes + Hesperidin + Carvacrol. Following a 6-week (42-day) experimental period, systemic necropsy was performed. Renal tissues were evaluated histopathologically using Periodic Acid\u2013Schiff, Masson\u2019s trichrome, and Best Carmine staining. Immunohistochemical analyses were conducted to assess Bcl-2, Bax, Caspase-3, Caspase-9 expression, and apoptotic cell death using the TUNEL assay. Results: Histopathological analysis demonstrated significant differences in tubular dilatation, intracellular vacuolization, and mesangial matrix expansion among groups (p &lt; 0.05), whereas tubular atrophy, hyaline accumulation, mononuclear cell infiltration, and the number of sclerotic glomeruli were not significantly different (p &gt; 0.05). Treatment with hesperidin and carvacrol significantly attenuated renal injury and fibrosis in diabetic rats (p &lt; 0.001). Diabetic kidneys exhibited increased immunopositivity for Bax, Caspase-3, and Caspase-9 and decreased Bcl-2 expression (p &lt; 0.001). Combined hesperidin and carvacrol treatment markedly reduced apoptotic cell numbers compared with the untreated diabetic group (p &lt; 0.001). Conclusions: The combined administration of hesperidin and carvacrol exerts protective effects against diabetic nephropathy, potentially through modulation of the Bcl-2\/Bax-mediated apoptotic pathway and attenuation of renal fibrosis.<\/jats:p>","DOI":"10.3390\/life16071067","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1067","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Protective Effects of Carvacrol and Hesperidin in Rats with Streptozotocin-Induced Diabetic Nephropathy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-4952","authenticated-orcid":false,"given":"Nil\u00fcfer","family":"Kuruca","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine, Department of Pathology, Ondokuz Mayis University, 55189 Samsun, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1468-3415","authenticated-orcid":false,"given":"Tolga","family":"G\u00fcven\u00e7","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Department of Pathology, Ondokuz Mayis University, 55189 Samsun, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.5812\/nephropathol.9093","article-title":"Diabetic nephropathy and antioxidants","volume":"2","author":"Tavafi","year":"2013","journal-title":"J. Nephropathol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dkhil, M.A., Zrieq, R., Al-Quraishy, S., and Abdel Moneim, A.E. (2016). Selenium nanoparticles attenuate oxidative stress and testicular damage in streptozotocin-induced diabetic rats. Molecules, 21.","DOI":"10.3390\/molecules21111517"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Betteridge, D.J., and Soran, H. (2014). Kidney disease in diabetes. Managing Cardiovascular Complications in Diabetes, John Wiley & Sons, Ltd.","DOI":"10.1002\/9781118337967"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.semnephrol.2007.01.012","article-title":"Histopathology of diabetic nephropathy","volume":"27","author":"Fioretto","year":"2007","journal-title":"Semin. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.jfda.2016.08.009","article-title":"Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin\u2013nicotinamide induced diabetic nephropathy","volume":"25","author":"Kishore","year":"2017","journal-title":"J. Food Drug Anal."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Agte, V., and Gite, S. (2019). Diabetic cataract and role of antiglycating phytochemicals. Handbook of Nutrition, Diet, and the Eye, Elsevier.","DOI":"10.1016\/B978-0-12-815245-4.00016-8"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/10942912.2011.595864","article-title":"Anti-diabetic potential of phenolic compounds: A review","volume":"16","year":"2013","journal-title":"Int. J. Food Prop."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bbrc.2015.04.030","article-title":"Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1,2-dimethyl hydrazine plus dextran sodium sulfate-induced inflammation associated carcinogenicity in the colon of Fischer 344 rats","volume":"461","author":"Arigesavan","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1076\/1388-0209(200004)3821-1FT106","article-title":"Essential oils of annual Sideritis species growing in Turkey","volume":"38","author":"Kirimer","year":"2000","journal-title":"Pharm. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1002\/ptr.6103","article-title":"Carvacrol and human health: A comprehensive review","volume":"32","author":"Varoni","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1177\/0960327117735572","article-title":"Benzo(a)pyrene induces lung toxicity and inflammation in mice: Prevention by carvacrol","volume":"37","author":"Barnwal","year":"2018","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.biopha.2018.12.054","article-title":"The ameliorative effect of carvacrol on oxidative stress and germ cell apoptosis in testicular tissue of adult diabetic rats","volume":"111","author":"Shoorei","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/jbt.20355","article-title":"Protective effect of carvacrol on oxidative stress and cellular DNA damage induced by UVB irradiation in human peripheral lymphocytes","volume":"29","author":"Aristatile","year":"2015","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/j.1742-7843.2010.00609.x","article-title":"Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol","volume":"107","author":"Oliveira","year":"2010","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.31989\/ffhd.v2i6.90","article-title":"Development of functional food products in relation to obesity","volume":"2","author":"Choudhary","year":"2012","journal-title":"Funct. Foods Health Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s11655-012-1120-0","article-title":"Natural products: A safest approach for obesity","volume":"18","author":"Vasudeva","year":"2012","journal-title":"Chin. J. Integr. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1021\/jf000613v","article-title":"Inhibitors of 15-lipoxygenase from orange peel","volume":"48","author":"Malterud","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.biopha.2018.10.001","article-title":"Investigation of the effects of hesperidin and chrysin on renal injury induced by colistin in rats","volume":"108","author":"Hanedan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0278-6915(90)90168-M","article-title":"Carcinogenicity study of methyl hesperidin in B6C3F1 mice","volume":"28","author":"Kurata","year":"1990","journal-title":"Food Chem. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1271\/bbb.90576","article-title":"Hypoglycemic and hypolipidemic effects of hesperidin and cyclodextrin-clathrated hesperetin in Goto-Kakizaki rats with type 2 diabetes","volume":"73","author":"Akiyama","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.biopha.2017.10.102","article-title":"Antihyperglycemic effect of hesperetin, a citrus flavonoid, extenuates hyperglycemia and explores antioxidant and antihyperlipidemic potential in streptozotocin-induced diabetic rats","volume":"97","author":"Jayaraman","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3164\/jcbn.09-82","article-title":"Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats","volume":"46","author":"Akiyama","year":"2009","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1093\/jn\/133.6.1892","article-title":"Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice","volume":"133","author":"Chiba","year":"2003","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tirkey, N., Pilkhwal, S., Kuhad, A., and Chopra, K. (2005). Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacol., 5.","DOI":"10.1186\/1471-2210-5-2"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.nutres.2004.07.005","article-title":"Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology","volume":"24","author":"Erlund","year":"2004","journal-title":"Nutr. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.biopha.2017.03.102","article-title":"The effect of hesperidin and quercetin on oxidative stress, NF-\u03baB and SIRT1 levels in a STZ-induced experimental diabetes model","volume":"90","author":"Iskender","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"167","DOI":"10.4103\/pm.pm_41_17","article-title":"The effects of hesperidin and quercetin on serum tumor necrosis factor-alpha and interleukin-6 levels in a streptozotocin-induced diabetes model","volume":"14","author":"Dokumacioglu","year":"2018","journal-title":"Pharmacogn. Mag."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.3390\/nu9121312","article-title":"Protective effects of hesperidin (citrus flavanone) on high glucose-induced oxidative stress and apoptosis in a cellular model for diabetic retinopathy","volume":"9","author":"Liu","year":"2017","journal-title":"Nutrients"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116858","DOI":"10.1016\/j.lfs.2019.116858","article-title":"Hesperidin ameliorates pancreatic \u03b2-cell dysfunction and apoptosis in streptozotocin-induced diabetic rat model","volume":"235","author":"Hanchang","year":"2019","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Atta, M.S., Almadaly, E.A., El-Far, A.H., Saleh, R.M., Assar, D.H., Al Jaouni, S.K., and Mousa, S.A. (2017). Thymoquinone defeats diabetes-induced testicular damage in rats targeting antioxidant, inflammatory and aromatase expression. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050919"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/1573399810666140606111745","article-title":"Diabetes mellitus induced impairment of male reproductive functions: A review","volume":"10","year":"2014","journal-title":"Curr. Diabetes Rev."},{"key":"ref_32","first-page":"369","article-title":"Plants having potential antidiabetic activity: A review","volume":"2","author":"Chauhan","year":"2010","journal-title":"Pharm. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"McElwain, C.J., McCarthy, F.P., and McCarthy, C.M. (2021). Gestational diabetes mellitus and maternal immune dysregulation: What we know so far. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084261"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2337\/db16-0806","article-title":"Differentiation of diabetes by pathophysiology, natural history, and prognosis","volume":"66","author":"Skyler","year":"2017","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1161\/ATVBAHA.116.307302","article-title":"Impact of diabetes mellitus","volume":"36","author":"Kanter","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13020-021-00485-4","article-title":"Flavonoids on diabetic nephropathy: Advances and therapeutic opportunities","volume":"16","author":"Hu","year":"2021","journal-title":"Chin. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1001\/jama.287.19.2570","article-title":"Diabetes and atherosclerosis: Epidemiology, pathophysiology, and management","volume":"287","author":"Beckman","year":"2002","journal-title":"JAMA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jnutbio.2004.06.006","article-title":"Protective effect of Montilla-Moriles appellation red wine on oxidative stress induced by streptozotocin in the rat","volume":"15","author":"Montilla","year":"2004","journal-title":"J. Nutr. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejphar.2011.01.021","article-title":"DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice","volume":"656","author":"Gajski","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neulet.2008.02.051","article-title":"The impact of bodyweight and body condition on behavioral testing for painful diabetic neuropathy in the streptozotocin rat model","volume":"436","author":"Hoybergs","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jep.2010.05.031","article-title":"Effect of Vaccinium bracteatum Thunb. leaves extract on blood glucose and plasma lipid levels in streptozotocin-induced diabetic mice","volume":"130","author":"Wang","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1523-1755.57.s75.5.x","article-title":"Glomerular hypertension, abnormal glomerular growth, and progression of renal diseases","volume":"57","author":"Fogo","year":"2000","journal-title":"Kidney Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s001250050012","article-title":"Expression of cytoskeletal proteins during the course of experimental diabetic nephropathy","volume":"43","author":"Sanai","year":"2000","journal-title":"Diabetologia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"179","DOI":"10.25000\/acem.452530","article-title":"Renoprotective potential of quercetin in experimental diabetic nephropathy: Assessing antiapoptotic and antioxidant effects","volume":"3","author":"Hafize","year":"2018","journal-title":"Arch. Clin. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s10735-008-9201-2","article-title":"The effects of ACE inhibitor and angiotensin receptor blocker on clusterin and apoptosis in the kidney tissue of streptozotocin-diabetic rats","volume":"39","author":"Ozturk","year":"2008","journal-title":"J. Mol. Histol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1177\/0960327114531995","article-title":"Amelioration of streptozotocin-induced diabetic nephropathy","volume":"34","author":"Elbe","year":"2015","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"bqab234","DOI":"10.1210\/endocr\/bqab234","article-title":"Podocyte bioenergetics in the development of diabetic nephropathy: The role of mitochondria","volume":"163","author":"Audzeyenka","year":"2022","journal-title":"Endocrinology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chang, J., Zheng, J., Gao, X., Dong, H., Yu, H., Huang, M., Sun, Z., and Feng, X. (2022). TangShenWeiNing formula prevents diabetic nephropathy by protecting podocytes through the SIRT1\/HIF-1\u03b1 pathway. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.888611"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Canbaz, H.T., Sozen, M.E., Cinar Ayan, I., Savas, H.B., Canbaz, F.A., Cuce, G., and Kalkan, S. (2025). Effects of carvacrol on oxidative stress and fibrosis in streptozotocin-induced diabetic nephropathy: Histological, gene expression, and biochemical insights. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010291"},{"key":"ref_50","first-page":"1","article-title":"The histologic alterations of experimental diabetes on the rat kidneys","volume":"12","author":"Ozturk","year":"2005","journal-title":"Inonu Univ. Med. Fac. J."},{"key":"ref_51","first-page":"145","article-title":"Improving effects of melatonin on the histologic alterations of rat kidneys induced by experimental diabetes","volume":"12","author":"Vardi","year":"2005","journal-title":"Ann. Med. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4103\/0973-029X.164531","article-title":"Periodic acid Schiff-diastase as a key in exfoliative cytology in diabetics: A pilot study","volume":"19","author":"Latti","year":"2015","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1097\/00000478-200604000-00012","article-title":"Glycogenic hepatopathy: An underrecognized hepatic complication of diabetes mellitus","volume":"30","author":"Torbenson","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.diabres.2008.09.017","article-title":"Role of reactive oxygen species in the pathogenesis of diabetic nephropathy","volume":"82","author":"Ha","year":"2008","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/35008121","article-title":"Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage","volume":"404","author":"Nishikawa","year":"2000","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"F455","DOI":"10.1152\/ajprenal.00137.2002","article-title":"High glucose promotes mesangial cell apoptosis by oxidant-dependent mechanisms","volume":"284","author":"Kang","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"F1013","DOI":"10.1152\/ajprenal.00209.2003","article-title":"IGF-1 inhibits the mitochondrial apoptosis program in mesangial cells exposed to high glucose","volume":"285","author":"Kang","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1136\/jim-50-06-04","article-title":"Taurine prevents apoptosis induced by high ambient glucose in human tubule renal cells","volume":"50","author":"Verzola","year":"2002","journal-title":"J. Investig. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1177\/108155899704500207","article-title":"Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys","volume":"45","author":"Ortiz","year":"1997","journal-title":"J. Investig. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.02-0130fje","article-title":"High glucose-induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases","volume":"17","author":"Allen","year":"2003","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.3390\/biomedicines10112863","article-title":"The role of NF-\u03baB and Bax\/Bcl-2\/Caspase-3 signaling pathways in the protective effects of sacubitril\/valsartan (Entresto) against HFD\/STZ-induced diabetic kidney disease","volume":"10","author":"Mohany","year":"2022","journal-title":"Biomedicines"},{"key":"ref_63","first-page":"680","article-title":"Targeting programmed cell death in diabetic kidney disease","volume":"22","author":"Liu","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hashimoto, K., Yoshida, Y., Kamesawa, M., Yazawa, N., Tominaga, H., Aisyah, R., Chen, S., Bumrungkit, C., Kawamoto, S., and Kumrungsee, T. (2025). Glucosyl hesperidin supplementation prevents tubulointerstitial fibrosis and immune activation in diabetic nephropathy in mice. Nutrients, 17.","DOI":"10.3390\/nu17030383"},{"key":"ref_65","first-page":"1235","article-title":"Promising influences of hesperidin and hesperetin against diabetes and its complications: A systematic review of molecular, cellular, and metabolic effects","volume":"22","author":"Mirzaei","year":"2023","journal-title":"EXCLI J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/path.1289","article-title":"Comparison of immunohistochemistry for activated caspase-3 and cleaved cytokeratin 18 with the TUNEL method for quantification of apoptosis in histological sections of PC-3 subcutaneous xenografts","volume":"199","author":"Duan","year":"2003","journal-title":"J. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4142\/jvs.2011.12.1.65","article-title":"The expressions of HSP70 and \u03b1B-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs","volume":"12","author":"Gulbahar","year":"2011","journal-title":"J. Vet. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3109\/10520295.2012.736637","article-title":"Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin","volume":"88","author":"Guvenc","year":"2013","journal-title":"Biotech. Histochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1177\/019262339902700419","article-title":"The nomenclature of cell death: Recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists","volume":"27","author":"Levin","year":"1999","journal-title":"Toxicol. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1046\/j.1523-1755.2000.00188.x","article-title":"Apoptotic regulatory proteins in renal injury","volume":"58","author":"Ortiz","year":"2000","journal-title":"Kidney Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.1159\/000076749","article-title":"Tubular and interstitial cell apoptosis in the streptozotocin-diabetic rat kidney","volume":"96","author":"Kumar","year":"2004","journal-title":"Nephron Exp. Nephrol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/7\/1067\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:26:47Z","timestamp":1782966407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/7\/1067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":71,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["life16071067"],"URL":"https:\/\/doi.org\/10.3390\/life16071067","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}