{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:32:41Z","timestamp":1785893561432,"version":"3.56.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Ovarian ischemia\/reperfusion (I\/R) injury is a common gynecological emergency, typically caused by ovarian torsion. Pirfenidone (PFN) has demonstrated potential therapeutic benefits due to its antioxidant, anti-inflammatory, and antiapoptotic properties. This research aimed to investigate the protective effects of PFN in alleviating ovarian I\/R injury in female rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female rats received PFN (300\u00a0mg\/kg\/day) for 3 consecutive days, either with or without the induction of ovarian I\/R. The study assessed markers of ovarian oxidative stress, inflammation, apoptosis, and the levels of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor-A (VEGF-A). Ovarian histology was analyzed, along with immunohistochemical staining for Toll-like receptor 4 (TLR4) and p38 mitogen-activated protein kinase (p38 MAPK).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>I\/R injury resulted in increased oxidative stress, inflammation, apoptosis, and a significant reduction in ovarian VEGF-A levels. Histological examination revealed ovarian damage, with increased expression of TLR4 and p38 MAPK. PFN treatment significantly improved the hormonal balance and mitigated oxidative stress, inflammatory, and apoptotic markers to normal levels. In addition, PFN improved ovarian tissue morphology and decreased TLR4 and p38 MAPK expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The findings suggest that PFN may offer protective effects against ovarian I\/R injury through its antioxidant, anti-inflammatory, and antiapoptotic properties, as well as by promoting angiogenesis in the ovary.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf066","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T11:47:29Z","timestamp":1753357649000},"page":"1583-1592","source":"Crossref","is-referenced-by-count":4,"title":["Protective effect of pirfenidone against ovarian ischemia\/reperfusion injury in rats via modulation of TLR4\/p38 MAPK\/IL-1\u03b2 and HIF-1\u03b1\/VEGF-A signaling pathways"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6184-2901","authenticated-orcid":false,"given":"Asmaa Mohamed","family":"Abdel-Aziz","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina Moustafa","family":"Thabit","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba A","family":"Shawky","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embryology, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar Hisham","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa Mohamed","family":"Khalaf","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Minia University , Minia 61511 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"2025110409522149400_ref1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.14744\/tjtes.2024.27388","article-title":"Etomidate alleviates ovarian ischemia-reperfusion injury in rats","volume":"30","author":"K\u00f6l\u00fck\u00e7\u00fc","year":"2024","journal-title":"Ulus Travma Acil Cerrahi Derg"},{"key":"2025110409522149400_ref2","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1080\/10520295.2021.1961863","article-title":"Effects of vitamin B12 on rat ovary with ischemia-reperfusion injury","volume":"97","author":"Kaplan","year":"2022","journal-title":"Biotech Histochem"},{"key":"2025110409522149400_ref3","doi-asserted-by":"publisher","first-page":"e20201586","DOI":"10.1590\/0001-3765202320201586","article-title":"The effects of metyrosine on ischemia-reperfusion-induced oxidative ovarian injury in rats: biochemical and histopathological assessment","volume":"95","author":"Yapca","year":"2023","journal-title":"An Acad Bras Cienc"},{"key":"2025110409522149400_ref4","doi-asserted-by":"publisher","first-page":"108417","DOI":"10.1016\/j.reprotox.2023.108417","article-title":"Artemisinin reduces acute ovarian ischemia-reperfusion injury in rats","volume":"119","author":"Osmanl\u0131o\u011flu","year":"2023","journal-title":"Reprod Toxicol"},{"key":"2025110409522149400_ref5","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/1477-7827-10-49","article-title":"The effects of oxidative stress on female reproduction: a review","volume":"10","author":"Agarwal","year":"2012","journal-title":"Reprod Biol Endocrinol"},{"key":"2025110409522149400_ref6","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/ph16020168","article-title":"Empagliflozin protects against haloperidol experimentally-induced ovarian toxicity","volume":"16","author":"Abdelzaher","year":"2023","journal-title":"Pharmaceuticals (Basel)"},{"key":"2025110409522149400_ref7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2478\/enr-2023-0004","article-title":"Leptin alleviated ovarian ischemia-reperfusion injury in rats via modulation of Sirt-1\/Nrf2 and TLR4\/NF-kB\/caspase-3 signaling pathways","volume":"57","author":"Abdel-Hamid","year":"2023","journal-title":"Endocr Regul"},{"key":"2025110409522149400_ref8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.22074\/IJFS.2021.522550.1069","article-title":"Protective effect of minocycline on Bax and Bcl-2 gene expression, histological damages and oxidative stress induced by ovarian torsion in adult rats","volume":"16","author":"Khaje Roshanaee","year":"2022","journal-title":"Int J Fertil Steril"},{"key":"2025110409522149400_ref9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.22074\/ijfs.2021.540364.1200","article-title":"The impact of chrysin on the folliculogenesis and ovarian apoptosis in ischemia-reperfusion injury in the rat model","volume":"16","author":"Mohammadi","year":"2022","journal-title":"Int J Fertil Steril"},{"key":"2025110409522149400_ref10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.tjog.2020.10.004","article-title":"Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative\/nitrosative stress","volume":"60","author":"Demir","year":"2021","journal-title":"Taiwan J Obstet Gynecol"},{"key":"2025110409522149400_ref11","doi-asserted-by":"publisher","first-page":"8729","DOI":"10.1038\/s41598-024-59395-8","article-title":"Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats","volume":"14","author":"Amirkhosravi","year":"2024","journal-title":"Sci Rep"},{"key":"2025110409522149400_ref12","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1165\/rcmb.2019-0328TR","article-title":"Pirfenidone: molecular mechanisms and potential clinical applications in lung disease","volume":"62","author":"Ruwanpura","year":"2020","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2025110409522149400_ref13","doi-asserted-by":"publisher","first-page":"e2023036","DOI":"10.36141\/svdld.v40i3.13847","article-title":"Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin","volume":"40","author":"Demirkol","year":"2023","journal-title":"Sarcoidosis Vasc Diffuse Lung Dis"},{"key":"2025110409522149400_ref14","first-page":"20","article-title":"Effects of pirfenidone on experimental head injury in rats","volume":"15","author":"Bozkurt","year":"2022","journal-title":"Int J Clin Exp Pathol"},{"key":"2025110409522149400_ref15","doi-asserted-by":"publisher","first-page":"118454","DOI":"10.1016\/j.lfs.2020.118454","article-title":"Pirfenidone attenuates gentamicin-induced acute kidney injury by inhibiting inflammasome-dependent NLRP3 pathway in rats","volume":"260","author":"Sharawy","year":"2020","journal-title":"Life Sci"},{"key":"2025110409522149400_ref16","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1159\/000523711","article-title":"Effects of oral pirfenidone on colon anastomosis healing and adhesion formation in rats","volume":"63","author":"Betancourt-Vicencio","year":"2022","journal-title":"Eur Surg Res"},{"key":"2025110409522149400_ref17","doi-asserted-by":"publisher","first-page":"122539","DOI":"10.1016\/j.ijpharm.2022.122539","article-title":"Innovated pirfenidone loaded lecithin nanocapsules for targeting liver fibrosis: formulation, characterization and in vivo study","volume":"631","author":"AbouSamra","year":"2023","journal-title":"Int J Pharm"},{"key":"2025110409522149400_ref18","doi-asserted-by":"publisher","first-page":"880","DOI":"10.2459\/JCM.0000000000001534","article-title":"Effects of pirfenidone on scar size and ventricular remodeling after myocardial infarction: a preclinical study","volume":"24","author":"Aimo","year":"2023","journal-title":"J Cardiovasc Med (Hagerstown)"},{"key":"2025110409522149400_ref19","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.3892\/etm.2018.6378","article-title":"Pirfenidone suppresses bleomycin-induced pulmonary fibrosis and periostin expression in rats","volume":"16","author":"Song","year":"2018","journal-title":"Exp Ther Med"},{"key":"2025110409522149400_ref20","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/s41443-019-0152-9","article-title":"The effect of an antifibrotic agent, pirfenidone, on penile erectile function in an experimental rat model of ischemic priapism","volume":"32","author":"Cinar","year":"2020","journal-title":"Int J Impot Res"},{"key":"2025110409522149400_ref21","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/pros.23995","article-title":"The effect of pirfenidone on rat chronic prostatitis\/chronic pelvic pain syndrome and its mechanisms","volume":"80","author":"Peng","year":"2020","journal-title":"Prostate"},{"key":"2025110409522149400_ref22","doi-asserted-by":"crossref","DOI":"10.1007\/s11357-024-01322-w","article-title":"Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse","volume-title":"GeroScience","author":"Amargant"},{"key":"2025110409522149400_ref23","doi-asserted-by":"publisher","first-page":"176721","DOI":"10.1016\/j.ejphar.2024.176721","article-title":"Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats","volume":"977","author":"Ko","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"2025110409522149400_ref24","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3760\/cma.j.cn121094-20211008-00489","article-title":"Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats","volume":"41","author":"Yan","year":"2023","journal-title":"Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi"},{"key":"2025110409522149400_ref25","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/jog.13524","article-title":"What is the protective effect of metformin on rat ovary against ischemia-reperfusion injury?","volume":"44","author":"Dayangan Sayan","year":"2018","journal-title":"J Obstet Gynaecol Res"},{"key":"2025110409522149400_ref26","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1186\/s12917-024-04219-0","article-title":"The effect of norethisterone acetate on the uterus of albino rats: histological, histochemical and ultrastructure study","volume":"20","author":"Abd-Elkareem","year":"2024","journal-title":"BMC Vet Res"},{"key":"2025110409522149400_ref27","doi-asserted-by":"publisher","first-page":"e50928","DOI":"10.1371\/journal.pone.0050928","article-title":"Sodium selenite improves folliculogenesis in radiation-induced ovarian failure: a mechanistic approach","volume":"7","author":"Said","year":"2012","journal-title":"PLoS One"},{"key":"2025110409522149400_ref28","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1016\/j.ultrasmedbio.2014.02.006","article-title":"Effect of therapeutic ultrasound on folliculogenesis, angiogenesis and apoptosis after heterotopic mouse ovarian transplantation","volume":"40","author":"Abtahi","year":"2014","journal-title":"Ultrasound Med Biol"},{"key":"2025110409522149400_ref29","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1007\/s00404-020-05888-6","article-title":"Protective effect of edaravone against radiation-induced ovarian injury: a histopathological and immunohistochemical evaluation in an experimental rat model","volume":"303","author":"Mete Ural","year":"2021","journal-title":"Arch Gynecol Obstet"},{"key":"2025110409522149400_ref30","doi-asserted-by":"publisher","first-page":"112700","DOI":"10.1016\/j.intimp.2024.112700","article-title":"Protective effect of leukotriene receptor antagonist, montelukast, against cyclophosphamide-induced placental toxicity via modulation of NLRP3\/IL-1\u03b2 signaling pathway in rats","volume":"139","author":"Abdelzaher","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"2025110409522149400_ref31","doi-asserted-by":"publisher","first-page":"619","DOI":"10.2144\/000112776","article-title":"Twenty-five years of quantitative PCR for gene expression analysis","volume":"44","author":"VanGuilder","year":"2008","journal-title":"Biotechniques"},{"key":"2025110409522149400_ref32","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1080\/15376516.2020.1774829","article-title":"Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1","volume":"30","author":"Abdel-Aziz","year":"2020","journal-title":"Toxicol Mech Methods"},{"key":"2025110409522149400_ref33","doi-asserted-by":"publisher","first-page":"116840","DOI":"10.1016\/j.lfs.2019","article-title":"Underlying mechanisms behind the protective effect of angiotensin (1-7) in experimental rat model of ovarian ischemia reperfusion injury","volume":"15","author":"Ali","year":"2019","journal-title":"Life Sci"},{"key":"2025110409522149400_ref34","doi-asserted-by":"publisher","first-page":"e077469","DOI":"10.1136\/bmj-2023-077469","article-title":"Premature ovarian insufficiency","volume":"20","author":"Nash","year":"2024","journal-title":"BMJ"},{"key":"2025110409522149400_ref35","doi-asserted-by":"publisher","first-page":"1205901","DOI":"10.3389\/fendo.2023.1205901","article-title":"Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency","volume":"14","author":"Pu","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025110409522149400_ref36","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.22038\/IJBMS.2023.72544.15776","article-title":"Effect of trimetazidine against ovarian ischemia\/reperfusion injury in rat model: a new pathway: JAK2\/STAT3","volume":"26","author":"Yuksel","year":"2023","journal-title":"Iran J Basic Med Sci"},{"key":"2025110409522149400_ref37","doi-asserted-by":"publisher","first-page":"3415046","DOI":"10.1155\/2016\/3415046","article-title":"The protective effects of alpha-lipoic acid and coenzyme Q10 combination on ovarian ischemia-reperfusion injury: an experimental study","volume":"2016","author":"Tuncer","year":"2016","journal-title":"Adv Med"},{"key":"2025110409522149400_ref38","doi-asserted-by":"publisher","first-page":"6500587","DOI":"10.1155\/2023\/6500587","article-title":"The flavonoid chrysin protects against testicular apoptosis induced by torsion\/detorsion in adult rats","volume":"2023","author":"Abadi","year":"2023","journal-title":"Andrologia"},{"key":"2025110409522149400_ref39","doi-asserted-by":"publisher","first-page":"64","DOI":"10.4103\/cjp.cjp_3_22","article-title":"Functional and structural assessment of the possible protective effect of platelet-rich plasma against ischemia\/reperfusion-induced ovarian injury in adult rats","volume":"65","author":"Allam","year":"2022","journal-title":"Chin J Physiol"},{"key":"2025110409522149400_ref40","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.14744\/tjtes.2023.52986","article-title":"Protective effects of Passiflora incarnata on ovarian ischemia\/reperfusion damage in rats with ovarian torsion","volume":"29","author":"Arslan","year":"2023","journal-title":"Ulus Travma Acil Cerrahi Derg"},{"key":"2025110409522149400_ref41","doi-asserted-by":"publisher","first-page":"eabn4564","DOI":"10.1126\/sciadv.abn4564","article-title":"Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary","volume":"8","author":"Umehara","year":"2022","journal-title":"Sci Adv"},{"key":"2025110409522149400_ref42","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1007\/s00210-024-03407-x","article-title":"Pirfenidone targeted mechanisms for alleviating methotrexate-induced testiculopathy in Wistar rats","volume":"398","author":"Mersal","year":"2025","journal-title":"Naunyn Schmiedeberg\u2019s Arch Pharmacol"},{"key":"2025110409522149400_ref43","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3390\/ijms19041057","article-title":"Emerging roles of vascular cell adhesion molecule-1 (VCAM-1) in immunological disorders and cancer","volume":"19","author":"Kong","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2025110409522149400_ref44","doi-asserted-by":"publisher","first-page":"111063","DOI":"10.1016\/j.biopha.2020.111063","article-title":"Diacerein protects rats with liver ischemia\/reperfusion damage: down-regulation of TLR4\/ NF\u03ba-B signaling pathway","volume":"134","author":"Ibrahim","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"2025110409522149400_ref45","doi-asserted-by":"publisher","first-page":"715354","DOI":"10.3389\/fphar.2021.715354","article-title":"Rivaroxaban modulates TLR4\/Myd88\/NF-k\u03b2 signaling pathway in a dose-dependent manner with suppression of oxidative stress and inflammation in an experimental model of depression","volume":"12","author":"Abdelzaher","year":"2021","journal-title":"Front Pharmacol"},{"key":"2025110409522149400_ref46","doi-asserted-by":"publisher","first-page":"3765898","DOI":"10.1155\/2019\/3765898","article-title":"Aloin preconditioning attenuates hepatic ischemia\/reperfusion injury via inhibiting TLR4\/MyD88\/NF-\u03baB signal pathway in vivo and in vitro","volume":"2019","author":"Du","year":"2019","journal-title":"Oxidative Med Cell Longev"},{"key":"2025110409522149400_ref47","doi-asserted-by":"publisher","first-page":"117435","DOI":"10.1016\/j.lfs.2020.117435","article-title":"The role of Toll-like receptor 4 signaling pathway in ovarian, cervical, and endometrial cancers","volume":"247","author":"Lupi","year":"2020","journal-title":"Life Sci"},{"key":"2025110409522149400_ref48","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.3390\/ijms20051103","article-title":"Salidroside ameliorates renal interstitial fibrosis by inhibiting the TLR4\/NF-\u03baB and MAPK signaling pathways","volume":"20","author":"Li","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2025110409522149400_ref49","doi-asserted-by":"publisher","first-page":"176166","DOI":"10.1016\/j.ejphar.2023.176166","article-title":"Canagliflozin ameliorates ulcerative colitis via regulation of TLR4\/MAPK\/NF-\u03baB and Nrf2\/PPAR-\u03b3\/SIRT1 signaling pathways","volume":"960","author":"Althagafy","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"2025110409522149400_ref50","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1007\/s43440-020-00096-0","article-title":"Fenofibrate ameliorates testicular damage in rats with streptozotocin-induced type 1 diabetes: role of HO-1 and p38 MAPK","volume":"72","author":"Abdel-Aziz","year":"2020","journal-title":"Pharmacol Rep"},{"key":"2025110409522149400_ref51","doi-asserted-by":"publisher","first-page":"120431","DOI":"10.1016\/j.lfs.2022.120431","article-title":"Administration of hemin ameliorates ovarian ischemia reperfusion injury via modulation of heme oxygenase-1 and p-JNK\/p-NF-\u03baBp65\/iNOS signaling pathway","volume":"1","author":"Ali","year":"2022","journal-title":"Life Sci"},{"key":"2025110409522149400_ref52","doi-asserted-by":"publisher","first-page":"108676","DOI":"10.1016\/j.intimp.2022.108676","article-title":"The effects of vitamin B12 on the TLR-4\/NF-\u03baB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation","volume":"107","author":"Deniz","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"2025110409522149400_ref53","doi-asserted-by":"publisher","first-page":"292","DOI":"10.5653\/cerm.2023.06366","article-title":"The effects of berberine on ischemia-reperfusion injuries in an experimental model of ovarian torsion","volume":"50","author":"Yilmaz","year":"2023","journal-title":"Clin Exp Reprod Med"},{"key":"2025110409522149400_ref54","doi-asserted-by":"publisher","first-page":"57","DOI":"10.22514\/j.androl.2024.015","article-title":"Regulation of STAT3 and NF-\u03baB signaling pathways by trans-anethole in testicular ischemia-reperfusion injury and its gonadoprotective effect","volume":"22","author":"Seker","year":"2024","journal-title":"Rev Int Androl"},{"key":"2025110409522149400_ref55","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41401-021-00706-4","article-title":"Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A","volume":"43","author":"Cao","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"2025110409522149400_ref56","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3390\/cells12070994","article-title":"Modeling the effects of cypermethrin toxicity on ovalbumin-induced allergic pneumonitis rats: macrophage phenotype differentiation and p38\/STAT6 signaling are candidate targets of pirfenidone treatment","volume":"12","author":"Morsi","year":"2023","journal-title":"Cells"},{"key":"2025110409522149400_ref57","doi-asserted-by":"publisher","first-page":"117086","DOI":"10.1016\/j.taap.2024.117086","article-title":"Protective effect of rupatadine on testicular ischemia\/reperfusion injury in rats: modulation of IL-6\/STAT3, Akt\/mTOR signaling pathways","volume":"492","author":"Abdel-Aziz","year":"2024","journal-title":"Toxicol Appl Pharmacol"},{"key":"2025110409522149400_ref58","first-page":"111","article-title":"Role of vascular endothelial growth factor in ovarian physiology\u2014an overview","volume":"5","author":"Kaczmarek","year":"2005","journal-title":"Reprod Biol"},{"key":"2025110409522149400_ref59","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1177\/0960327120960775","article-title":"Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats","volume":"40","author":"Ibrahim","year":"2021","journal-title":"Hum Exp Toxicol"},{"key":"2025110409522149400_ref60","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1007\/s00408-018-0140-8","article-title":"Tissue and bronchoalveolar lavage biomarkers in idiopathic pulmonary fibrosis patients on pirfenidone","volume":"196","author":"Ronan","year":"2018","journal-title":"Lung"},{"key":"2025110409522149400_ref61","doi-asserted-by":"publisher","first-page":"121048","DOI":"10.1016\/j.lfs.2022.121048","article-title":"Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and\/or anti-SARS-CoV-2","volume":"309","author":"Antar","year":"2022","journal-title":"Life Sci"},{"key":"2025110409522149400_ref62","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.pharep.2019.04.005","article-title":"Protective role of pirfenidone against experimentally-induced pancreatitis","volume":"71","author":"El-Kashef","year":"2019","journal-title":"Pharmacol Rep"},{"key":"2025110409522149400_ref63","doi-asserted-by":"publisher","first-page":"108289","DOI":"10.1016\/j.intimp.2021.108289","article-title":"A novel role of pirfenidone in attenuation acetic acid induced ulcerative colitis by modulation of TGF-\u03b21\/JNK1 pathway","volume":"101","author":"Antar","year":"2021","journal-title":"Int Immunopharmacol"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/77\/11\/1583\/64034695\/rgaf066.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/77\/11\/1583\/64034695\/rgaf066.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:52:29Z","timestamp":1762267949000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/77\/11\/1583\/8233144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":63,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,8,13]]},"published-print":{"date-parts":[[2025,10,30]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgaf066","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,8,13]]}}}