TY  - JOUR
T1  - Evaluation of the Effects of Acute Cisplatin Administration on Testicular and Ovarian Tissue in Rats
TT  - Sıçanlarda Akut Sisplatin Uygulamasının Testis ve Yumurtalık Dokusundaki Etkilerinin Değerlendirilmesi
AU  - Yalçın, Betül
AU  - Kalkan, Kübra Tuğçe
AU  - Çarkıt, Sedat
AU  - Cengiz Mat, Özge
AU  - Önder, Gözde Özge
AU  - Yay, Arzu
PY  - 2025
DA  - April
Y2  - 2025
DO  - 10.18678/dtfd.1597470
JF  - Duzce Medical Journal
JO  - Duzce Med J
PB  - Duzce University
WT  - DergiPark
SN  - 1307-671X
SP  - 88
EP  - 94
VL  - 27
IS  - 1
LA  - en
AB  - Aim: Cisplatin, one of the effective chemotherapeutics in cancer treatment, has the potential to affect the testis and ovary, leading to permanent or temporary infertility. This study aimed to determine the acute effects of cisplatin on testis and ovary histology and to investigate whether it induces any changes in immunohistochemical cyclooxygenase-2 (COX2), nuclear factor kappa B p65 (NFκB-p65), and heat-shock protein 70 (HSP70) levels.Material and Methods: The study was planned as four groups: male control, male cisplatin, female control, and female cisplatin. The cisplatin group rats were adminestered with 7 mg/kg cisplatin, and all rats were sacrificed 24 hours later. Hematoxylin-eosin and Masson's trichrome stains were applied to testis and ovary tissues to examine their histopathological structure, and an immunohistochemistry staining protocol was applied to determine immunostaining intensity of COX2, NFκB-p65, and HSP70.Results: In the cisplatin group, a decrease in seminiferous tubule epithelium, an elevation in fibrotic response in the interstitial area, and a notable reduction in Johnson testicular biopsy score (p
KW  - cisplatin
KW  - testis
KW  - ovary
KW  - cyclooxygenase-2
KW  - NF-kappa B p65
KW  - heat-shock protein 70
N2  - Amaç: Kanser tedavisinde etkili kemoterapötiklerden biri olan sisplatin, testis ve overi etkileyerek kalıcı veya geçici infertiliteye yol açma potansiyeline sahiptir. Bu çalışma, sisplatinin testis ve over histolojisi üzerindeki akut etkilerini belirlemeyi ve immünohistokimyasal siklooksijenaz-2 (COX2), nükleer faktör kappa B p65 (NFκB-p65) ve ısı-şok protein 70 (HSP70) düzeylerinde herhangi bir değişikliğe neden olup olmadığını araştırmayı amaçlamıştır.Gereç ve Yöntemler: Çalışma dört grup olarak planlandı: erkek kontrol, erkek sisplatin, dişi kontrol ve dişi sisplatin. Sisplatin grubu sıçanlara 7 mg/kg sisplatin uygulandı ve tüm sıçanlar 24 saat sonra sakrifiye edildi. Testis ve over dokularına histopatolojik yapılarını incelemek amacıyla hematoksilen-eozin ve Masson trikrom boyaları uygulandı ve COX2, NFκB-p65 ve HSP70'in immün boyama yoğunluğunu belirlemek amacıyla immünohistokimya boyama protokolü uygulandı.Bulgular: Sisplatin grubunda, testiste seminifer tübül epitelinde azalma, interstisyel alanda fibrotik yanıtta artış ve Johnson testiküler biyopsi skorunda kayda değer bir azalma (p
CR  - Mezencev R. Interactions of cisplatin with non-DNA targets and their influence on anticancer activity and drug toxicity: the complex world of the platinum complex. Curr Cancer Drug Targets. 2015;14(9):794-816.
CR  - Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 2019;88:102925.
CR  - Aldossary SA. Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J. 2019;12(1):7-15.
CR  - Qari M, Harakeh S, Akefe IO, Saber SH, Al-Raddadi R, Abd Elmageed ZY, et al. Pomegranate nanoparticle mitigates cisplatin-induced testicular toxicity and improves cisplatin anti-cancer efficacy in Ehrlich carcinoma model. J King Saud Univ Sci. 2023;35(4):102631.
CR  - Khan R, Khan AQ, Qamar W, Lateef A, Tahir M, Rehman MU, et al. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: probable role of p38MAPK and p53. Toxicol Appl Pharmacol. 2012;258(3):315-29.
CR  - Negm WA, El-Kadem AH, Hussein IA, Alqahtani MJ. The mechanistic perspective of bilobetin protective effects against cisplatin-induced testicular toxicity: Role of Nrf-2/Keap-1 signaling, inflammation, and apoptosis. Biomedicines. 2022;10(5):1134.
CR  - Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol. 2017;13(5):525-36.
CR  - Lopes F, Tholeti P, Adiga SK, Anderson RA, Mitchell RT, Spears N. Chemotherapy induced damage to spermatogonial stem cells in prepubertal mouse in vitro impairs long-term spermatogenesis. Toxicol Rep. 2020;8:114-23.
CR  - Ince S, Ozer M, Kadioglu BG, Kuzucu M, Ozkaraca M, Gezer A, et al. The effect of taxifolin on oxidative ovarian damage and reproductive dysfunctions induced by antipsychotic drugs in female rats. J Obstet Gynaecol Res. 2021;47(6):2140-8.
CR  - Liman N. Heat shock proteins (HSP)-60, -70, -90, and 105 display variable spatial and temporal immunolocalization patterns in the involuting rat uterus. Anim Reprod. 2017;14(4):1072-86.
CR  - Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C. Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol. 2007;81(1):15-27.
CR  - Lavie L, Dyugovskaya L, Golan-Shany O, Lavie P. Heat-shock protein 70: expression in monocytes of patients with sleep apnoea and association with oxidative stress and tumour necrosis factor-alpha. J Sleep Res. 2010;19(1 Pt 2):139-47.
CR  - Suemasu S, Tanaka K, Namba T, Ishihara T, Katsu T, Fujimoto M, et al. A role for HSP70 in protecting against indomethacin-induced gastric lesions. J Biol Chem. 2009;284(29):19705-15.
CR  - Benzer F, Kandemir FM, Kucukler S, Comaklı S, Caglayan C. Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in Wistar rats: by modulating inflammatory cytokines, apoptosis, oxidative stress, and oxidative DNA damage. Arch Physiol Biochem. 2018;124(5):448-57.
CR  - Elshawi OE, Nabeel AI. Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation. J Photochem Photobiol B. 2019;192:90-6.
CR  - Hassan MH, Ghobara M, Abd-Allah GM. Modulator effects of meloxicam against doxorubicin-induced nephrotoxicity in mice. J Biochem Mol Toxicol. 2014;28(8):337-46.
CR  - Sahu BD, Rentam KK, Putcha UK, Kuncha M, Vegi GM, Sistla R. Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity. Food Chem Toxicol. 2011;49(12):3090-7.
CR  - Ibrahim MA, Albahlol IA, Wani FA, Abd-Eltawab Tammam A, Kelleni MT, Sayeed MU, et al. Resveratrol protects against cisplatin-induced ovarian and uterine toxicity in female rats by attenuating oxidative stress, inflammation and apoptosis. Chem Biol Interact. 2021;338:109402.
CR  - Johnson L, Petty CS, Neaves WB. The relationship of biopsy evaluation and testicular measurement to over-all daily sperm production in human testes. Fertil Steril 1980;34(1):36-40.
CR  - Alqahtani MJ, Negm WA, Saad HM, Salem EA, Hussein IA, Ibrahim HA. Fenofibrate and Diosmetin in a rat model of testicular toxicity: New insight on their protective mechanism through PPAR-α/NRF-2/HO-1 signaling pathway. Biomed Pharmacother. 2023;165:115095.
CR  - Dinc K, Ozyurt R, Coban TA, Yazici GN, Suleyman Z, Yavuzer B, et al. The effect of carvacrol on the proinflammatory cytokines, histology, and fertility outcome of cisplatin-related ovarian change in a rat model. Taiwan J Obstet Gynecol. 2023;62(2):256-63.
CR  - Ayazoglu Demir E, Mentese A, Livaoglu A, Turkmen Alemdar N, Demir S. Ameliorative effect of gallic acid on cisplatin-induced ovarian toxicity in rats. Drug Chem Toxicol. 2023;46(1):97-103.
CR  - Al-Shahat A, Hulail MAE, Soliman NMM, Khamis T, Fericean LM, Arisha AH, et al. Melatonin mitigates cisplatin-induced ovarian dysfunction via altering steroidogenesis, inflammation, apoptosis, oxidative stress, and PTEN/PI3K/Akt/mTOR/AMPK signaling pathway in female rats. Pharmaceutics. 2022;14(12):2769.
CR  - Othman EM, Habib HA, Zahran ME, Amin A, Heeba GH. Mechanistic protective effect of cilostazol in cisplatin-induced testicular damage via regulation of oxidative stress and TNF-α/NF-κB/caspase-3 pathways. Int J Mol Sci. 2023;24(16):12651.
CR  - Ashtari A, Niazvand F, Chamkouri N, Mohammadi A, Karami AB. The ameliorative effects of Alpinia officinarum rhizome hydroalcoholic extract on cisplatin-induced testicular toxicity in rats. JBRA Assist Reprod. 2023;27(1):41-8.
CR  - Hokmabadi A, Ranjbar E, Alipour F, Ebrahimzadeh-Bideskan A, Afshari JT, Rezaei MM, et al. Protective effect of dental pulp stem cells' conditioned medium against cisplatin-induced testicular damage in rats. Toxicology. 2024;504:153788.
CR  - Demir EA. Syringic acid alleviates cisplatin-induced ovarian injury through modulating endoplasmic reticulum stress, inflammation and Nrf2 pathway. J Trace Elem Med Biol. 2024;82:127356.
CR  - Chtourou Y, Aouey B, Kebieche M, Fetoui H. Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways. Chem Biol Interact. 2015;239:76-86.
CR  - Jarosz M, Olbert M, Wyszogrodzka G, Młyniec K, Librowski T. Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology. 2017;25(1):11-24.
CR  - Song J, Hong H, Ko JI, Park EJ, Park SM, Son SY, et al. Structure and nuclear transport mechanism of Hsp70 nuclear transporter, Hikeshi. BioDesign. 2015;3(3):117-22.
CR  - Kandil B, Kurtdede N, Bayraktaroglu AG. Immunohistochemical localization and expression of heat shock proteins (HSP27, HSP60, HSP70, and HSP90) during the oestrous cycle, pregnancy, and lactation in rat ovaries. Acta Histochem. 2024;126(3):152157.
CR  - Dokladny K, Lobb R, Wharton W, Ma TY, Moseley PL. LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-kappaB. Cell Stress Chaperones. 2010;15(2):153-63.
CR  - Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod. 2001;65(1):229-39.
CR  - Park SH, Park K, Park YI. Effects of temperature change on heat shock protein 70 expression in rat testes. Korean J Urol. 2003;44(2):186-91.
CR  - Mobaraki F, Seghatoleslam M, Fazel A, Ebrahimzadeh-Bideskan A. Effects of MDMA (ecstasy) on apoptosis and heat shock protein (HSP70) expression in adult rat testis. Toxicol Mech Methods. 2018;28(3):219-29.
CR  - Narayansingh RM, Senchyna M, Vijayan MM, Carlson JC. Expression of prostaglandin G/H synthase (PGHS) and heat shock protein-70 (HSP-70) in the corpus luteum (CL) of prostaglandin F2 alpha-treated immature superovulated rats. Can J Physiol Pharmacol. 2004;82(6):363-71.
CR  - Wu G, Hu X, Ding J, Yang J. Abnormal expression of HSP70 may contribute to PCOS pathology. J Ovarian Res. 2019;12(1):74.
UR  - https://doi.org/10.18678/dtfd.1597470
L1  - https://dergipark.org.tr/en/download/article-file/4421984
ER  -