{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:47:41Z","timestamp":1788821261140,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["NSTC 111-2313-B-005-052-MY3"],"award-info":[{"award-number":["NSTC 111-2313-B-005-052-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Inflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia\/reperfusion (I\/R) injury was investigated in this research. Five groups of six animals each were created: ischemia, Ischemia+Reperfusion (I+R), Ischemia+Reperfusion+Bromelain (I+R+Bro; 10 mg\/kg), control (sham), and Bromelain (Bro; 10 mg\/kg). An I\/R damage resulted from two hours of 720\u00b0 clockwise twisting of the left testis. Blood samples and epididymal sperm were collected after reperfusion to analyze sperm parameters (recovery, motility, viability, and morphology) and cytokines that promote inflammation (IL-1\u03b2, IL-6, and TNF-\u03b1). Using Western blotting, testicular tissue was examined for histopathological alterations, antioxidant enzymes (GSH, SOD), lipid peroxidation (MDA), apoptosis, and survival-related proteins (TLR4, Caspase-3, Bcl-2, NRF-2, HO-1, PI3K, mTOR, AKT-1). While raising the activities of GSH and SOD, two antioxidant enzymes, Bro administration dramatically reduced MDA concentrations. The I+R+Bro group had significantly reduced amounts of cytokines that promoted inflammation compared to the I+R group. Bro\u2019s protective properties are also attributed to proteins that are altered by it and participate in the apoptosis and survival of cells. Sperm morphology, motility, and concentration notably improved in the bromelain-treated group, according to spermatological examination. Testicular samples treated with bromelain showed less tissue damage according to histological evaluations than the untreated I+R group. These findings imply that Bro has anti-inflammatory, anti-apoptotic, and antioxidant qualities. It effectively reduces oxidative stress and inflammation by modulating the PI3K\/Akt\/mTOR and NRF-2\/HO-1 pathways, hence minimizing I\/R injury.<\/jats:p>","DOI":"10.3390\/biom15020292","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T07:48:22Z","timestamp":1739778502000},"page":"292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Protective Effects of Bromelain in Testicular Torsion-Detorsion: Reducing Inflammation, Oxidative Stress, and Apoptosis While Enhancing Sperm Quality"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-5661","authenticated-orcid":false,"given":"Seda","family":"Yakut","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur 15030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Karabulut","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Veterinary Medicine, Bing\u00f6l University, Bing\u00f6l 12000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Recep Hakk\u0131","family":"Koca","sequence":"additional","affiliation":[{"name":"Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Bing\u00f6l University, Bing\u00f6l 12000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Erba\u015f","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Atat\u00fcrk University, Erzurum 25240, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se\u00e7kin","family":"\u00d6zkanlar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine, Atat\u00fcrk University, Erzurum 25240, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berrin Tarak\u00e7\u0131","family":"Gen\u00e7er","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Veterinary Medicine, F\u0131rat University, Elaz\u0131\u011f 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adem","family":"Kara","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum 25100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8310-0546","authenticated-orcid":false,"given":"K. J. Senthil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Thandalam, Chennai 602105, Tamil Nadu, India"},{"name":"Center for General Education, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1111\/andr.13418","article-title":"Testicular torsion in vivo models: Mechanisms and treatments","volume":"11","author":"Minas","year":"2023","journal-title":"Andrology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12969-019-0334-5","article-title":"Testicular ischemia in deficiency of adenosine deaminase 2 (DADA2)","volume":"17","author":"Clarke","year":"2019","journal-title":"Pediatr. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.3892\/etm.2017.4289","article-title":"Medical perspective in testicular ischemia-reperfusion injury","volume":"13","author":"Arena","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Almarzouq, D., and Al-Maghrebi, M. (2023). NADPH oxidase-mediated testicular oxidative imbalance regulates the TXNIP\/NLRP3 inflammasome axis activation after ischemia reperfusion injury. Antioxidants, 12.","DOI":"10.3390\/antiox12010145"},{"key":"ref_5","first-page":"100364","article-title":"Propolis ameliorates ischemia\/reperfusion-induced testicular damage by reducing oxidative stress","volume":"21","author":"Demir","year":"2023","journal-title":"Rev. Int. Androl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.22270\/jddt.v13i6.6106","article-title":"Investigation of the effect of quercetin in experimental ischemia-reperfusion injury model in rat testicle","volume":"13","author":"Gezer","year":"2023","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_7","first-page":"201","article-title":"The protective effects of citrulline on testicular injury induced by torsion and detorsion in adult male rats: An experimental study","volume":"25","author":"Nia","year":"2024","journal-title":"J. Reprod. Infertil."},{"key":"ref_8","first-page":"1603469","article-title":"Baicalein alleviates testicular ischemia-reperfusion injury in a rat model of testicular torsion-detorsion","volume":"2022","author":"Wei","year":"2022","journal-title":"Oxid. Med. Cell. Longiv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102459","DOI":"10.1016\/j.tice.2024.102459","article-title":"Proanthocyanidin alleviates testicular torsion\/detorsion-induced ischemia\/reperfusion injury in rats","volume":"89","author":"Kazak","year":"2024","journal-title":"Tissue Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chen, C.H., Hsia, C.C., Hu, P.A., Yeh, C.H., Chen, C.T., Peng, C.L., Wang, C.H., and Lee, T.S. (2022). Bromelain ameliorates atherosclerosis by activating the TFEB-mediated autophagy and antioxidant pathways. Antioxidants, 12.","DOI":"10.3390\/antiox12010072"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2478\/cipms-2020-0028","article-title":"Bromelain-based chemo-herbal combination effect on human cancer cells: In-vitro study on AGS and MCF7 proliferation and apoptosis","volume":"33","author":"Raeisi","year":"2020","journal-title":"Curr. Issues Pharm. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pezzani, R., Jimenez-Garcia, M., Capo, X., S\u00f6nmez G\u00fcrer, E., Sharopov, F., Rachel, T.Y.L., Ntieche Woutouoba, D., Rescigno, A., Peddio, S., and Zucca, P. (2023). Anticancer properties of bromelain: State-of-the-art and recent trends. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1068778"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e14584","DOI":"10.1111\/and.14584","article-title":"Effect of bromelain on sperm quality, testicular oxidative stress and expression of oestrogen receptors in BISPHENOL-A treated male mice","volume":"54","author":"Khazaeel","year":"2022","journal-title":"Andrologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.ijbiomac.2022.11.291","article-title":"Ameliorative effects of bromelain on aluminum-induced Alzheimer\u2019s disease in rats through modulation of TXNIP pathway","volume":"227","author":"Eraky","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","article-title":"A simple method for clinical assay of superoxide dismutase","volume":"34","author":"Sun","year":"1988","journal-title":"Clin. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0003-2697(66)90167-9","article-title":"Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems","volume":"16","author":"Placer","year":"1966","journal-title":"Anal. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1385\/BTER:93:1-3:141","article-title":"Nickel deficiency diminishes sperm quantity and movement in rats","volume":"93","author":"Yokoi","year":"2003","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_19","first-page":"138","article-title":"Wistar Albino S\u0131\u00e7anlarda Michauxia campanuloides L\u2019H\u00e9r.\u2019in Baz\u0131 Sperma Parametreleri \u00dczerine Etkisi","volume":"15","author":"Koca","year":"2020","journal-title":"Atat\u00fcrk Univ. Vet. Bilim. Derg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000178170","article-title":"Testicular biopsy score count\u2013a method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males","volume":"1","author":"Johnsen","year":"1970","journal-title":"Horm. Res. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/S0022-5347(17)49278-0","article-title":"Histological changes occurring in the contralateral testes of prepubertal rats subjected to various durations of unilateral spermatic cord torsion","volume":"133","author":"Cosentino","year":"1985","journal-title":"J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108654","DOI":"10.1016\/j.reprotox.2024.108654","article-title":"Usnic acid alleviates testicular ischemia\/reperfusion injury in rats by modulating endoplasmic reticulum stress","volume":"128","author":"Demir","year":"2024","journal-title":"Reprod. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"281.e1","DOI":"10.1016\/j.jpurol.2024.01.001","article-title":"The potential prophylactic and therapeutic impacts of niacin on ischemia\/reperfusion injury of testis","volume":"20","author":"Ganjiani","year":"2024","journal-title":"J. Pediatr. Urol."},{"key":"ref_24","first-page":"2817","article-title":"Protective effect of allicin on ischemia-reperfusion injury caused by testicular torsion-detorsion in rats","volume":"28","author":"Wei","year":"2024","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"El-Demerdash, F.M., Hussien, D.M., Ghanem, N.F., and Al-Farga, A.M. (2022). Bromelain modulates liver injury, hematological, molecular, and biochemical perturbations induced by aluminum via oxidative stress inhibition. BioMed Res. Int., 2022.","DOI":"10.1155\/2022\/5342559"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103509","DOI":"10.1016\/j.etap.2020.103509","article-title":"Nephroprotective role of bromelain against oxidative injury induced by aluminium in rats","volume":"80","author":"Baghdadi","year":"2020","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.tips.2019.04.007","article-title":"Prescient indices of activity: The application of functional system sensitivity to measurement of drug effect","volume":"40","author":"Kenakin","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105944","DOI":"10.1016\/j.jddst.2024.105944","article-title":"Syringic acid loaded silver nanoparticles protects ovarian ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress-mediated apoptosis","volume":"99","author":"Kara","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","article-title":"Reperfusion injury and reactive oxygen species: The evolution of a concept","volume":"6","author":"Granger","year":"2015","journal-title":"Redox Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.32345\/2664-4738.4.2023.05","article-title":"Histopathological changes and immunohistochemical characteristics of the testicle in children with subcompensated ischemia during acute torsion","volume":"19","author":"Volos","year":"2023","journal-title":"Med. Sci. Ukr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1055\/s-0031-1285841","article-title":"Immunological effects of acute testicular torsion on the contralateral testis in rats","volume":"21","author":"Schanaider","year":"2011","journal-title":"Eur. J. Pediatr. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1464-410X.2010.09481.x","article-title":"Protective effect of sivelestat, a neutrophil elastase inhibitor, on ipsilateral and contralateral testes after unilateral testicular ischaemia\u2013reperfusion injury in rats","volume":"107","author":"Tsounapi","year":"2011","journal-title":"BJU Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrurol.2014.135","article-title":"Mechanisms of testicular torsion and potential protective agents","volume":"11","author":"Karaguzel","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, J., Yan, Z., Wang, Q., Wei, S., Liu, Q., Liu, T., and Hu, Z. (2023). Pretreatment with remote ischemic conditioning attenuates testicular damage after testicular ischemia and reperfusion injury in rats. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0287987"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, L., Xiong, X., Wu, X., Ye, Y., Jian, Z., Zhi, Z., and Gu, L. (2020). Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00028"},{"key":"ref_36","first-page":"S62","article-title":"An Overview of Ischemia\u2013Reperfusion Injury: Review on Oxidative Stress and Inflammatory Response","volume":"54","author":"Tanyeli","year":"2022","journal-title":"Eurasian J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.jds.2022.09.018","article-title":"Bromelain inhibits the inflammation and senescence effect in diabetic periodontitis: A preliminary in vitro study","volume":"18","author":"Lu","year":"2023","journal-title":"J. Dent. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Weinzierl, A., Harder, Y., Schmauss, D., Menger, M.D., and Laschke, M.W. (2022). Bromelain protects critically perfused musculocutaneous flap tissue from necrosis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061449"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1007\/s11064-011-0561-8","article-title":"Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating expression of transcription factor Nrf2 and HO-1 in rats","volume":"36","author":"Ren","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2\/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"110714","DOI":"10.1016\/j.intimp.2023.110714","article-title":"The role of PI3K\/AKT signaling pathway in myocardial ischemia-reperfusion injury","volume":"123","author":"Deng","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Stanciu, S.M., Jinga, M., Miricescu, D., Stefani, C., Nica, R.I., Stanescu-Spinu, I.-I., Vacaroiu, I.A., Greabu, M., and Nica, S. (2024). mTOR Dysregulation, Insulin Resistance, and Hypertension. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081802"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jebur, A.B., El-Demerdash, F.M., and Kang, W. (2020). Bromelain from Ananas comosus stem attenuates oxidative toxicity and testicular dysfunction caused by aluminum in rats. J. Trace Elem. Med. Biol., 62.","DOI":"10.1016\/j.jtemb.2020.126631"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"440.e1","DOI":"10.1016\/j.jpurol.2021.03.031","article-title":"The effect of intratesticular dexpanthenol on experimentally-induced testicular ischaemia\/reperfusion injury","volume":"17","author":"Ecer","year":"2021","journal-title":"J. Pediatr. Urol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:35:16Z","timestamp":1760027716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/2\/292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,15]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["biom15020292"],"URL":"https:\/\/doi.org\/10.3390\/biom15020292","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,15]]}}}