{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:57:33Z","timestamp":1780433853547,"version":"3.54.1"},"reference-count":37,"publisher":"Knowledge E DMCC","issue":"9","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["knepublishing.com"],"crossmark-restriction":true},"short-container-title":["IJRM"],"abstract":"<jats:p>Background: Di (2-ethylhexyl) phthalate (DEHP) is one of the environmental contaminants used in plastic objects, causing damage to the reproductive system. Chrysin (CHr) is an effective flavonoid in honey propolis with antioxidant activities.\r\nObjective: This study aimed to investigate the possible protective effects of CHr on DEHP-induced testicular toxicity in male mice.\r\nMaterials and Methods: In this experimental study, 50 male NMRI mice (4\u20136 wk, 20\u201330 gr) were randomly divided into 5 groups (n = 10\/each); group I and II received normal saline and oil, group III received DEHP, group IV received DEHP and CHr, group V were intact treated with CHr. Testis weights were measured. Serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels were evaluated. Also, sperm characteristics and histological changes of the testis were analyzed.\r\nResults: Testis weight was decreased in group receiving DEHP. DEHP also reduced the number of sperms, but the administration of CHr improved them. CHr ameliorated DEHP-induced changes in hormonal levels, especially testosterone (p &lt; 0.01). Morphological evaluation of the testis of DEHP-received mice indicated degenerated germ cells with vacuolated cytoplasm, wide intercellular spaces between germinal layers, and loss of spermatozoa in the center of lumens, all of them improved by CHr.\r\nConclusion: According to our biochemical and histopathological analyses, DEHP led to severe testicular injury. Our results suggest that CHr, as a free radical scavenger, can decrease tissue damage induced by DEHP, be beneficial in alleviating the toxic effects of DEHP on the male reproductive system, and can also be useful in preventing DEHP effects.<\/jats:p>","DOI":"10.18502\/ijrm.v23i9.20159","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:21:53Z","timestamp":1762003313000},"page":"713-722","update-policy":"https:\/\/doi.org\/10.18502\/knecrossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Protective effect of chrysin on di (2-ethylhexyl) phthalate-induced toxicity in mice testis: An experimental study"],"prefix":"10.18502","volume":"23","author":[{"given":"Zahra Matin","family":"Manesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Zeinali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ghanbari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afsaneh","family":"Mafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Goudarzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdiieh","family":"Ghoddoosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Hajihashemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Heidari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7770","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"307868","doi-asserted-by":"crossref","unstructured":"[1] Jenkins R, Farnbach K, Iragorri S. Elimination of intravenous di-2-ethylhexyl phthalate exposure abrogates most neonatal hypertension in premature infants with bronchopulmonary dysplasia. Toxics 2021; 9: 75.","DOI":"10.3390\/toxics9040075"},{"key":"307869","doi-asserted-by":"crossref","unstructured":"[2] Chiang C, Mahalingam S, Flaws JA. Environmental contaminants affecting fertility and somatic health. Semin Reprod Med 2017; 35: 241\u2013249.","DOI":"10.1055\/s-0037-1603569"},{"key":"307870","doi-asserted-by":"crossref","unstructured":"[3] Lin Y, Xu W, Yang L, Chen Z, Zhai J, Zhu Q, et al. Mechanism of testicular injury induced by Di-ethylhexyl phthalate and its protective agents. Chem Biol Interact 2023; 381: 110575.","DOI":"10.1016\/j.cbi.2023.110575"},{"key":"307871","doi-asserted-by":"crossref","unstructured":"[4] Khasin LG, Della Rosa J, Petersen N, Moeller J, Kriegsfeld LJ, Lishko PV. The impact of di-2-ethylhexyl phthalate on sperm fertility. Front Cell Dev Biol 2020; 8: 426.","DOI":"10.3389\/fcell.2020.00426"},{"key":"307872","doi-asserted-by":"crossref","unstructured":"[5] Hosseinzadeh A, Mehrzadi S, Siahpoosh A, Basir Z, Bahrami N, Goudarzi M. Gallic acid ameliorates di-(2-ethylhexyl) phthalate-induced testicular injury in adult mice. Hum Exp Toxicol 2022; 41: 9603271221078867.","DOI":"10.1177\/09603271221078867"},{"key":"307873","doi-asserted-by":"crossref","unstructured":"[6] Oudir M, Chader H, Bouzid B, Bendisari K, Latreche B, Boudalia S, et al. Male rat exposure to low dose of di(2-ethylhexyl) phthalate during pre-pubertal, pubertal and post-pubertal periods: Impact on sperm count, gonad histology and testosterone secretion. Reprod Toxicol 2018; 75: 33\u201339.","DOI":"10.1016\/j.reprotox.2017.11.004"},{"key":"307874","doi-asserted-by":"crossref","unstructured":"[7] Sadeghi A, Ghahari L, Yousefpour M. Vitamin E supplementation reduces oxidative stress in the male wistar rats\u2019 brain against polyvinyl chloride products. Ann Mil Health Sci Res 2019; 17: e92768.","DOI":"10.5812\/amh.92768"},{"key":"307875","doi-asserted-by":"crossref","unstructured":"[8] Bahrami N, Mehrzadi S, Goudarzi M, Mansouri E, Fatemi I. Lycopene abrogates di-(2-ethylhexyl) phthalate induced testicular injury by modulating oxidative, endocrine and inflammatory changes in mice. Life Sci 2018; 207: 265\u2013271.","DOI":"10.1016\/j.lfs.2018.06.009"},{"key":"307876","doi-asserted-by":"crossref","unstructured":"[9] Hu Q, Liu Z, Guo Y, Lu S, Du H, Cao Y. Antioxidant capacity of flavonoids from Folium Artemisiae argyi and the molecular mechanism in Caenorhabditis elegans. J Ethnopharmacol 2021; 279: 114398.","DOI":"10.1016\/j.jep.2021.114398"},{"key":"307877","doi-asserted-by":"crossref","unstructured":"[10] Mani R, Natesan V. Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry 2018; 145: 187\u2013196.","DOI":"10.1016\/j.phytochem.2017.09.016"},{"key":"307878","doi-asserted-by":"crossref","unstructured":"[11] Yosefi S, Madanchi H, Pakdel A, Kokhaei P, Hemati M, Sarmadi N, et al. Combinatorial effects of chrysin with doxorubicin, 5-fluorouracil, and cyclophosphamide on triple-negative breast cancer cell line. Iran J Pharm Res 2025; 24: e157446.","DOI":"10.5812\/ijpr-157446"},{"key":"307879","doi-asserted-by":"crossref","unstructured":"[12] Del Fabbro L, Bortolotto VC, Ferreira LM, Sari MHM, Furian AF. Chrysin\u2019s anti-inflammatory action in the central nervous system: A scoping review and an evidence-gap mapping of its mechanisms. Eur J Pharmacol 2025; 997: 177602.","DOI":"10.1016\/j.ejphar.2025.177602"},{"key":"307880","doi-asserted-by":"crossref","unstructured":"[13] Sabry HA, Zahra MM, Haredy ShA, Amer AS. Neuroprotective impacts of chrysin against clonazepam induced cognitive deficits in male rats. J Appl Pharm Sci 2023; 13: 174\u2013185.","DOI":"10.7324\/JAPS.2023.13885"},{"key":"307881","doi-asserted-by":"crossref","unstructured":"[14] Vakili A, Momenabadi S, Bandegi AR, Vafaei AA, Vakili A. Chrysin and gallic acid protect the hippocampal neurons and mitigate blood-brain barrier disruption in a mouse model of global cerebral ischemia. Jundishapur J Nat Pharm Prod 2025; 20: e159908.","DOI":"10.5812\/jjnpp-159908"},{"key":"307882","doi-asserted-by":"crossref","unstructured":"[15] Shang J, Jiao J, Yan M, Wang J, Li Q, Shabuerjiang L, et al. Chrysin protects against cerebral ischemia-reperfusion injury in hippocampus via restraining oxidative stress and transition elements. Biomed Pharmacother 2023; 161: 114534.","DOI":"10.1016\/j.biopha.2023.114534"},{"key":"307883","doi-asserted-by":"crossref","unstructured":"[16] Naz S, Imran M, Rauf A, Orhan IE, Shariati MA, Shahbaz M, et al. Chrysin: Pharmacological and therapeutic properties. Life Sci 2019; 235: 116797.","DOI":"10.1016\/j.lfs.2019.116797"},{"key":"307884","doi-asserted-by":"crossref","unstructured":"[17] Aksu EM, Ozkaraca F, Kandemir A, Omur E, Eldutar S, Comakl\u0131 S. Mitigation of paracetamol-induced reproductive damage by chrysin in male rats via reducing oxidative stress. Andrologia 2016; 48: 1145\u20131154.","DOI":"10.1111\/and.12553"},{"key":"307885","doi-asserted-by":"crossref","unstructured":"[18] Altawash ASA, Shahneh H, Ansari M. Chrysin-induced sperm parameters and fatty acid profile changes improve reproductive performance of roosters. Theriogenology 2017; 104: 72\u201379.","DOI":"10.1016\/j.theriogenology.2017.07.022"},{"key":"307886","doi-asserted-by":"crossref","unstructured":"[19] Shoieb SMA, Esmat AE, Abdel-Naim AB. Chrysin attenuates testosterone-induced benign prostate hyperplasia in rats. Food Chem Toxic 2018; 111: 650\u2013659.","DOI":"10.1016\/j.fct.2017.12.017"},{"key":"307887","doi-asserted-by":"crossref","unstructured":"[20] Zeinali M, Hosseinzadeh H. An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomed Pharmacother 2017; 92: 998\u20131009.","DOI":"10.1016\/j.biopha.2017.06.003"},{"key":"307888","doi-asserted-by":"crossref","unstructured":"[21] Khani S, Abdollahi M, Asadi Z, Nazeri M, Nasiri MA, Yusefi H, et al. Hypoglycemic, hepatoprotective, and hypolipidemic effects of hydroalcoholic extract of Eryngium billardieri root on nicotinamide\/streptozotocin-induced type II diabetic rats. Res Pharm Sci 2021; 16: 193\u2013202.","DOI":"10.4103\/1735-5362.310526"},{"key":"307889","unstructured":"[22] Alboghobeish S, Mahdavinia M, Zeidooni L, Samimi A, Oroojan AA, Alizadeh S, et al. Efficiency of naringin against reproductive toxicity and testicular damages induced by bisphenol A in rats. Iran J Basic Med Sci 2019; 22: 315\u2013323."},{"key":"307890","doi-asserted-by":"crossref","unstructured":"[23] Heidari H, Abdollahi M, Khani S, Nojavan F, Khani S. Effect of Alpinia officinarum extract on reproductive damages in streptozotocin induced diabetic male rats. J Diabetes Metab Disord 2021; 20: 77\u201385.","DOI":"10.1007\/s40200-020-00711-0"},{"key":"307891","doi-asserted-by":"crossref","unstructured":"[24] Goudarzi M, Kalantar M, Kalantar H. The hepatoprotective effect of gallic acid on mercuric chloride-induced liver damage in rats. Jundishapur J Nat Pharm Prod 2018; 12: e12345.","DOI":"10.5812\/jjnpp.12345"},{"key":"307892","doi-asserted-by":"crossref","unstructured":"[25] Goudarzi M, Haghi Karamallah M, Malayeri A, Kalantar M, Mansouri E, Kalantar H. Protective effect of alpha-lipoic acid on di-(2-ethylhexyl) phthalate-induced testicular toxicity in mice. Environ Sci Pollut Res Int 2020; 27: 13670\u201313678.","DOI":"10.1007\/s11356-020-07817-1"},{"key":"307893","doi-asserted-by":"crossref","unstructured":"[26] Mesquita I, Lorigo M, Cairrao E. Update about the disrupting-effects of phthalates on the human reproductive system. Mol Reprod Dev 2021; 88: 650\u2013672.","DOI":"10.1002\/mrd.23541"},{"key":"307894","doi-asserted-by":"crossref","unstructured":"[27] Han L, Wang J, Zhao T, Wu Y, Wei Y, Chen J, et al. Stereological analysis and transcriptome profiling of testicular injury induced by di-(2-ethylhexyl) phthalate in prepubertal rats. Ecotoxicol Environ Saf 2021; 220: 112326.","DOI":"10.1016\/j.ecoenv.2021.112326"},{"key":"307895","doi-asserted-by":"crossref","unstructured":"[28] Wang Y, Ni C, Li X, Lin Z, Zhu Q, Li L, et al. Phthalate-induced fetal leydig cell dysfunction mediates male reproductive tract anomalies. Front Pharmacol 2019; 10: 1309.","DOI":"10.3389\/fphar.2019.01309"},{"key":"307896","doi-asserted-by":"crossref","unstructured":"[29] Abd El-Fattah AA, Fahim AT, Sadik NAH, Ali BM. Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats. Gen Comp Endocrinol 2016; 225: 45\u201354.","DOI":"10.1016\/j.ygcen.2015.09.006"},{"key":"307897","doi-asserted-by":"crossref","unstructured":"[30] Hong Y, Zhou Y, Shen L, Wei Y, Long C, Fu Y, et al. Exposure to DEHP induces testis toxicity and injury through the ROS\/mTOR\/NLRP3 signaling pathway in immature rats. Ecotoxicol Environ Saf 2021; 227: 112889.","DOI":"10.1016\/j.ecoenv.2021.112889"},{"key":"307898","doi-asserted-by":"crossref","unstructured":"[31] Dutta S, Sengupta P, Slama P, Roychoudhury S. Oxidative stress, testicular inflammatory pathways, and male reproduction. Int J Mol Sci 2021; 22: 10043.","DOI":"10.3390\/ijms221810043"},{"key":"307899","doi-asserted-by":"crossref","unstructured":"[32] Yadav P, Chand Mali P. Testicular inflammation in male reproductive system. Explor Immunol 2024; 4: 446\u2013464.","DOI":"10.37349\/ei.2024.00151"},{"key":"307900","doi-asserted-by":"crossref","unstructured":"[33] Yu Z, Wang F, Han J, Lu R, Li Q, Cai L, et al. Opposite effects of high- and low-dose di-(2-ethylhexyl) phthalate (DEHP) exposure on puberty onset, oestrous cycle regularity and hypothalamic kisspeptin expression in female rats. Reprod Fertil Dev 2020; 32: 610\u2013618.","DOI":"10.1071\/RD19024"},{"key":"307901","doi-asserted-by":"crossref","unstructured":"[34] Mart\u00ednez-Ibarra A, Cerb\u00f3n M, Mart\u00ednez-Razo LD, Morales-Pacheco M, Torre-Villalvazo I, Kawa S, et al. Impact of DEHP exposure on female reproductive health: Insights into uterine effects. Environ Toxicol Pharmacol 2024; 107: 104391.","DOI":"10.1016\/j.etap.2024.104391"},{"key":"307902","doi-asserted-by":"crossref","unstructured":"[35] Bahrami N, Goudarzi M, Hosseinzadeh A, Sabbagh S, Reiter RJ, Mehrzadi S. Evaluating the protective effects of melatonin on di(2-ethylhexyl) phthalate-induced testicular injury in adult mice. Biomed Pharmacother 2018; 108: 515\u2013523.","DOI":"10.1016\/j.biopha.2018.09.044"},{"key":"307903","doi-asserted-by":"crossref","unstructured":"[36] Abbas MA, Alqaisi KM, Disi A, Hameed NA. Chrysin increased progesterone and LH levels, estrous phase duration and altered uterine histology without affecting aromatase expression in rat ovary. J Func Foods 2022; 89: 104964.","DOI":"10.1016\/j.jff.2022.104964"},{"key":"307904","doi-asserted-by":"crossref","unstructured":"[37] Belhan S, Y\u0131ld\u0131r\u0131m S, Karasu A, K\u00f6m\u00fcro\u011flu AU, \u00d6zdek U. Investigation of the protective role of chrysin within the framework of oxidative and inflammatory markers in experimental testicular ischaemia\/reperfusion injury in rats. Andrologia 2020; 52: e13714.","DOI":"10.1111\/and.13714"}],"container-title":["International Journal of Reproductive BioMedicine (IJRM)"],"original-title":[],"link":[{"URL":"https:\/\/knepublishing.com\/index.php\/ijrm\/article\/download\/20159\/30779","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/knepublishing.com\/index.php\/ijrm\/article\/download\/20159\/30779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:43:11Z","timestamp":1762004591000},"score":1,"resource":{"primary":{"URL":"https:\/\/knepublishing.com\/index.php\/ijrm\/article\/view\/20159"},"secondary":[{"URL":"http:\/\/ijrm.ir\/article-1-3594-en.html","label":"UNIVERSITY"}]},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,11,1]]}},"URL":"https:\/\/doi.org\/10.18502\/ijrm.v23i9.20159","relation":{},"ISSN":["2476-3772","2476-4108"],"issn-type":[{"value":"2476-3772","type":"electronic"},{"value":"2476-4108","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11,1]]}}}