{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:42:36Z","timestamp":1783449756749,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["RS-2022-00166535"],"award-info":[{"award-number":["RS-2022-00166535"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 \u00b1 0.48 g, whereas the STZ\/4HR group showed a significantly enhanced weight of 1.91 \u00b1 0.26 g (p &lt; 0.001), aligning closely with the control group\u2019s weight of 1.99 \u00b1 0.17 g and the 4HR group\u2019s weight of 2.05 \u00b1 0.24 g, indicating no significant difference between control and 4HR groups (p &gt; 0.05). Furthermore, the STZ\/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ\/4HR group relative to the STZ group (p &lt; 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.<\/jats:p>","DOI":"10.3390\/ijms25084316","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:24:26Z","timestamp":1713176666000},"page":"4316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats"],"prefix":"10.3390","volume":"25","author":[{"given":"Ji-Hyeon","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-8842","authenticated-orcid":false,"given":"Je-Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-4508","authenticated-orcid":false,"given":"Dae-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5088-2732","authenticated-orcid":false,"given":"Seong-Gon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-6725","authenticated-orcid":false,"given":"Umberto","family":"Garagiola","sequence":"additional","affiliation":[{"name":"Biomedical, Surgical and Oral Sciences Department, Maxillofacial and Dental Unit, School of Dentistry, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.dsx.2020.07.031","article-title":"Diabetes mellitus and the impairment of male reproductive function: Possible signaling pathways","volume":"14","author":"Ghorbanzadeh","year":"2020","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Panghal, A., and Jena, G. (Curr. Diabetes Rev., 2023). Gut-gonad perturbations in type-1 diabetes mellitus: Role of dysbiosis, oxidative stress, inflammation and energy-dysbalance, Curr. Diabetes Rev., Epub ahead of print.","DOI":"10.2174\/1573399820666230822151740"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/andr.13262","article-title":"Understanding and treating ejaculatory dysfunction in men with diabetes mellitus","volume":"11","author":"Desai","year":"2023","journal-title":"Andrology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/j.1743-6109.2008.01168.x","article-title":"Erectile dysfunction in diabetes mellitus","volume":"6","author":"Malavige","year":"2009","journal-title":"J. Sex. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/andr.13342","article-title":"Effects of diabetes mellitus on sperm quality and fertility outcomes: Clinical evidence","volume":"11","author":"Lotti","year":"2023","journal-title":"Andrology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1093\/humrep\/17.10.2673","article-title":"Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality","volume":"17","author":"Baccetti","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1210\/endo-108-4-1441","article-title":"Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells","volume":"108","author":"Adashi","year":"1981","journal-title":"Endocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0165-3806(84)90091-9","article-title":"Glucose utilization by the mouse brain: Influence of age and diabetes","volume":"317","author":"Garris","year":"1984","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0022-5347(17)43042-4","article-title":"The effect of streptozotocin-induced diabetes on the neuroendocrine-male reproductive tract axis of the adult rat","volume":"138","author":"Seethalakshmi","year":"1987","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.fct.2018.11.055","article-title":"Taurine ameliorates oxidative stress induced inflammation and ER stress mediated testicular damage in STZ-induced diabetic Wistar rats","volume":"124","author":"Ghosh","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.lfs.2015.09.015","article-title":"Rosuvastatin ameliorates diabetes-induced reproductive damage via suppression of oxidative stress, inflammatory and apoptotic pathways in male rats","volume":"141","author":"Heeba","year":"2015","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E163","DOI":"10.25011\/cim.v34i3.15189","article-title":"Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus","volume":"34","author":"Tabak","year":"2011","journal-title":"Clin. Investig. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"C1023","DOI":"10.1152\/ajpcell.2001.281.3.C1023","article-title":"Enhanced mitochondrial testicular antioxidant capacity in Goto-Kakizaki diabetic rats: Role of coenzyme Q","volume":"281","author":"Palmeira","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.intimp.2019.01.047","article-title":"Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation","volume":"70","author":"Khosravi","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"639","DOI":"10.4103\/1008-682X.186871","article-title":"Impact of antioxidants on seminal vesicles function and fertilizing potential in diabetic rats","volume":"19","author":"Tsounapi","year":"2017","journal-title":"Asian J. Androl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/13813455.2018.1543329","article-title":"Diabetes-induced testicular oxidative stress, inflammation, and caspase-dependent apoptosis: The protective role of metformin","volume":"126","author":"Nna","year":"2020","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"He, W., Liu, H., Hu, L., Wang, Y., Huang, L., Liang, A., Wang, X., Zhang, Q., Chen, Y., and Cao, Y. (2021). Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00851-9"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.1111\/jcmm.15198","article-title":"Loganin alleviates testicular damage and germ cell apoptosis induced by AGEs upon diabetes mellitus by suppressing the RAGE\/p38MAPK\/NF-\u03baB pathway","volume":"24","author":"Chen","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1139\/apnm-2018-0070","article-title":"Antioxidant, anti-inflammatory, and anti-apoptotic effects of zinc supplementation in testes of rats with experimentally induced diabetes","volume":"43","author":"Aziz","year":"2018","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alsieni, M.A., El Rabey, H.A., Al-Sieni, A.I., and Al-Seeni, M.N. (2021). Comparison between the antioxidant and antidiabetic activity of fenugreek and buckthorn in streptozotocin-induced diabetic male rats. Biomed. Res. Int., 2021.","DOI":"10.1155\/2021\/7202447"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/1744-7917.12154","article-title":"Effects of 4-hexylresorcinol on the phenoloxidase from Hyphantria cunea (Lepidoptera: Arctiidae): In vivo and in vitro studies","volume":"22","author":"Sharifi","year":"2015","journal-title":"Insect Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kim, D.W., Jo, Y.Y., Garagiola, U., Choi, J.Y., Kang, Y.J., Oh, J.H., and Kim, S.G. (2020). Increased level of vascular endothelial growth factors by 4-hexylresorcinol is mediated by transforming growth factor-beta1 and accelerates capillary regeneration in the burns in diabetic animals. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103473"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"863","DOI":"10.5650\/jos.ess22029","article-title":"The impact of some natural phenolic compounds on \u03b1-glucosidase and sorbitol dehydrogenase enzymes, and anti-leukemia cancer potential, spin density distributions, and in silico studies","volume":"71","author":"He","year":"2022","journal-title":"J. Oleo Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40902-022-00334-w","article-title":"4-Hexylresorcinol: Pharmacologic chaperone and its application for wound healing","volume":"44","author":"Kim","year":"2022","journal-title":"Maxillofac. Plast. Reconstr. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3892\/etm.2021.9785","article-title":"4-Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF-\u03baB signaling pathway and reverses bone loss in ovariectomized mice","volume":"21","author":"Yi","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jbiosc.2020.10.011","article-title":"Inhibitory potential of 4-hexylresorcinol against alpha-glucosidase and non-enzymatic glycation: Activity and mechanism","volume":"131","author":"Song","year":"2021","journal-title":"J. Biosci. Bioeng."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e13858","DOI":"10.1111\/and.13858","article-title":"Sitagliptin and fucoidan prevent apoptosis and reducing ER stress in diabetic rat testes","volume":"53","author":"Kizilay","year":"2021","journal-title":"Andrologia"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chilukoti, S.R., Sahu, C., and Jena, G. (2024). Protective role of eugenol against diabetes-induced oxidative stress, DNA damage, and apoptosis in rat testes. J. Biochem. Mol. Toxicol., 38.","DOI":"10.1002\/jbt.23593"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/cbf.3674","article-title":"The protective effect of metformin against testicular damage in diabetes and prostate cancer model","volume":"40","author":"Bugan","year":"2022","journal-title":"Cell Biochem. Funct."},{"key":"ref_30","first-page":"123","article-title":"Effects of glibenclamide and troxerutin on the sperm parameters and histopathological changes of testis in streptozotocin-induced diabetic male rats: An experimental study","volume":"21","author":"Shokri","year":"2023","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kucuk Baloglu, F., Guldag Tas, D., Yilmaz, O., and Severcan, F. (2023). The recovery effect of vitamin C on structural alterations due to Streptozotocin-Induced diabetes in rat testicular tissues. Spectrochim. Acta A Mol. Biomol. Spectrosc., 288.","DOI":"10.1016\/j.saa.2022.122149"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s10735-021-09957-1","article-title":"LGR4 silence aggravates ischemic injury by modulating mitochondrial function and oxidative stress via ERK signaling pathway in H9c2 cells","volume":"52","author":"Chen","year":"2021","journal-title":"J. Mol. Histol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gaida, D., Park, Y.W., and Kim, S.G. (2023). 4-Hexylresorcinol and its effects on circumvallate papillae taste buds in diabetic and healthy rats: An initial investigation. Appl. Sci., 13.","DOI":"10.3390\/app132111617"},{"key":"ref_34","first-page":"11039","article-title":"Protective effect of stevia on diabetic induced testicular damage: An immunohistochemical and ultrastructural study","volume":"27","author":"Elshafey","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zheng, H., Hu, Y., Shao, M., Chen, S., and Qi, S. (2023). Chromium picolinate protects against testicular damage in STZ-induced diabetic rats via anti-inflammation, anti-oxidation, inhibiting apoptosis, and regulating the TGF-\u03b21\/Smad pathway. Molecules, 28.","DOI":"10.3390\/molecules28227669"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155217","DOI":"10.1016\/j.phymed.2023.155217","article-title":"The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-\u03baB p65 inhibition","volume":"123","author":"Lu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Nna, V.U., Abu Bakar, A.B., Ahmad, A., Eleazu, C.O., and Mohamed, M. (2019). Oxidative stress, NF-\u03baB-mediated inflammation and apoptosis in the testes of streptozotocin-induced diabetic rats: Combined protective effects of Malaysian propolis and metformin. Antioxidants, 8.","DOI":"10.3390\/antiox8100465"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"145847","DOI":"10.1016\/j.gene.2021.145847","article-title":"Insulin treatment to type 1 male diabetic rats protects fertility by avoiding testicular apoptosis and cell cycle arrest","volume":"799","author":"Minas","year":"2021","journal-title":"Gene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1782953","DOI":"10.1155\/2019\/1782953","article-title":"Eucommia ulmoides Oliv. leaf extract improves erectile dysfunction in streptozotocin-induced diabetic rats by protecting endothelial function and ameliorating hypothalamic-pituitary-gonadal axis function","volume":"2019","author":"Fu","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5462","DOI":"10.1210\/jc.2004-0804","article-title":"Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes","volume":"89","author":"Dhindsa","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"bqab018","DOI":"10.1210\/endocr\/bqab018","article-title":"Mitochondria-Mediated Apoptosis Induced Testicular Dysfunction in Diabetic Rats: Ameliorative Effect of Resveratrol","volume":"162","author":"Aly","year":"2021","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1254\/fpj.72.493","article-title":"Experimental studies on anthelmintics (XXVI). Biochemical and pharmacological studies of 4-iodothymol on Ascaris lumbricoides suum","volume":"72","author":"Tanizawa","year":"1976","journal-title":"Nihon Yakurigaku Zasshi"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/tx800048m","article-title":"Identification of xenoestrogens in food additives by an integrated in silico and in vitro approach","volume":"22","author":"Amadasi","year":"2009","journal-title":"Chem. Res. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.acthis.2017.12.005","article-title":"Diabetes mellitus- induction: Effect of different streptozotocin doses on male reproductive parameters","volume":"120","author":"Omolaoye","year":"2018","journal-title":"Acta Histochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1292\/jvms.69.969","article-title":"Streptozotocin-induced diabetes increases apoptosis through JNK phosphorylation and Bax activation in rat testes","volume":"69","author":"Koh","year":"2007","journal-title":"J. Vet. Med. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Choi, K.H., Kim, D.W., Lee, S.K., Kim, S.G., and Kim, T.W. (2020). The Administration of 4-Hexylresorcinol Accelerates Orthodontic Tooth Movement and Increases the Expression Level of Bone Turnover Markers in Ovariectomized Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041526"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lee, I.S., Kim, D.W., Oh, J.H., Lee, S.K., Choi, J.Y., Kim, S.G., and Kim, T.W. (2021). Effects of 4-Hexylresorcinol on Craniofacial Growth in Rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168935"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4103\/2305-0500.321125","article-title":"Testicular oxidative stress and apoptosis status in streptozotocin-induced diabetic rats after treatment with rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia), and sutherlandia (Lessertia frutescens) infusions","volume":"10","author":"Omolaoye","year":"2021","journal-title":"Asian Pac. J. Reprod."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4316\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:27:33Z","timestamp":1760106453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084316"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084316","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,13]]}}}