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Sisplatin-indüklenmiş sıçan epididimis dokusunda rapamisin ve 3-metiladeninin etkilerinin histolojik olarak değerlendirilmesi

Yıl 2021, Cilt: 46 Sayı: 3, 1184 - 1190, 30.09.2021
https://doi.org/10.17826/cumj.924352

Öz

Amaç: Bu çalışmada sisplatin (Cis) doku üzerinde neden olduğu hasar üzerinde otofaji aktivatörü ve inhibitörü etkilerinin belirlenmesi amaçlanmıştır.
Gereç ve Yöntem: Çalışmada her grupta 6 hayvan olacak şekilde 24 adet Wistar albino cinsi erkek sıçan kullanıldı. Gruplar; Kontrol grubu, Sisplatin grubu (Cis) (8 mg/kg), Rapamisin (Rapa) grubu (2 mg/kg), 3-metiladenin grubu (3-MA) (15 mg/kg). Rapa ve 3-MA intraperitoneal 15 gün boyunca, Cis tek doz deneyin 7. Günü uygulandı. Deney sonunda epididimisler alındı. Histolojik teknikler sonrası alınan kesitlere Hematoksilen-Eozin ve Heat-shock-protein70 (HSP70) immunohistokimyası uygulandı.
Bulgular: Cis kesitlerinde tübül bazal membranında dağılma, tübül içinde vakuolizasyon gözlendi. Ayrıca bazı epitel hücrelerinin daha eozinofilik olduğu gözlendi. Rapa ve 3-MA ait doku kesitleri epitelizasyon, tübül bazal membranı olarak daha düzenli bir görünüme sahipti. HSP70 immunreaktivitesi tüm grupların tübüler arası bağ dokusunda gözlendi.
Sonuç: Semen kalitesi ve spermatozoanın potansiyelliğinin korunması için organın Cis gibi ajanlardan etkilendiği sonucuna varılmıştır. Rapa, Cis toksisitesine karşı epididimis üzerinde 3-MA’den daha etkili olabilir.

Destekleyen Kurum

Erciyes Üniversitesi

Proje Numarası

TSA-2019-8792

Teşekkür

Çalışmada yer alan tüm yazarlara ve destekleyen kuruma teşekkür ederim.

Kaynakça

  • Wang H, Kumar TR. Segment- and cell-specific expression of D-type cyclins in the postnatal mouse epididymis. Gene Expr Patterns2012 Mar-Apr;12(3-4):136-44.
  • Bezerra MS, Martins ABM, Trajano FMG, Pontes THA, Gomes L, Gavioli EC, et al. Fluoxetine and sertraline effects on rat distal cauda epididymis contraction, sperm count and sperm transit time trough epididymis. Eur J Pharmacol2019 Dec 15;865:172774.
  • Reddy KP, Madhu P, Reddy PS. Protective effects of resveratrol against cisplatin-induced testicular and epididymal toxicity in rats. Food Chem Toxicol2016 May;91:65-72.
  • Jahan S, Munawar A, Razak S, Anam S, Ain QU, Ullah H, et al. Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats. BMC Urol2018 Nov 21;18(1):107.
  • Soni KK, Kim HK, Choi BR, Karna KK, You JH, Cha JS, et al. Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress. Drug Des Devel Ther2016;10:3959-68.
  • Krawczyk Z, Gogler-Pigłowska A, Sojka DR, Scieglinska D. The Role of Heat Shock Proteins in Cisplatin Resistance. Anticancer Agents Med Chem2018;18(15):2093-109.
  • Shevtsov M, Huile G, Multhoff G. Membrane heat shock protein 70: a theranostic target for cancer therapy. Philos Trans R Soc Lond B Biol Sci2018 Jan 19;373(1738).
  • Rabinowitz JD, White E. Autophagy and metabolism. Science2010 Dec 3;330(6009):1344-8.
  • Ghasemnejad-Berenji M, Ghazi-Khansari M, Yazdani I, Saravi SSS, Nobakht M, Abdollahi A, et al. Rapamycin protects testes against germ cell apoptosis and oxidative stress induced by testicular ischemia-reperfusion. Iran J Basic Med Sci2017 Aug;20(8):905-11.
  • Liu S, Huang L, Geng Y, He J, Chen X, Xu H, et al. Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats. Mol Med Rep2017 Oct;16(4):4029-37.
  • Wang X, Zhou G, Liu C, Wei R, Zhu S, Xu Y, et al. Acanthopanax versus 3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats. Mediators Inflamm2016;2016:8369704.
  • Ceylan T, Kaymak E, Cantürk Tan F, Yakan B. Research on the protective effect of caffeic acid phenethyl ester on testicular damage caused by cisplatin. Turk J Med Sci2020 Dec 17;50(8):2032-9.
  • Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol2016 May;16(5):310-5.
  • Whirledge SD, Garcia JM, Smith RG, Lamb DJ. Ghrelin partially protects against cisplatin-induced male murine gonadal toxicity in a GHSR-1a-dependent manner. Biol Reprod2015 Mar;92(3):76.
  • Erdemli EA, Ergeneci D, Atahan Ş, IŞIKAY L. Cisplatinin siçan böbrek ve testisleri üzerine etkileri. 1999.
  • Liu J, Liu Y, Habeebu SS, Klaassen CD. Metallothionein (MT)-null mice are sensitive to cisplatin-induced hepatotoxicity. Toxicol Appl Pharmacol1998 Mar;149(1):24-31.
  • Zicca A, Cafaggi S, Mariggiò MA, Vannozzi MO, Ottone M, Bocchini V, et al. Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats. Eur J Pharmacol2002 May 10;442(3):265-72.
  • Sadzuka Y, Shoji T, Takino Y. Change of lipid peroxide levels in rat tissues after cisplatin administration. Toxicol Lett1991 Jul;57(2):159-66.
  • Sainath S, Sowbhagyamma T, Madhu P, Reddy KP, Girish B, Reddy PS. Protective effect of speman on cisplatin-induced testicular and epididymal toxicity in mice. International Journal of Green Pharmacy (IJGP)2011;5(4).
  • Vernet P, Aitken R, Drevet J. Antioxidant strategies in the epididymis. Molecular and cellular endocrinology2004;216(1-2):31-9.
  • Sadeghi N, Erfani-Majd N, Tavalaee M, Tabandeh MR, Drevet JR, Nasr-Esfahani MH. Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele. Oxid Med Cell Longev2020;2020:5140383.
  • Fang B, Xiao H. Rapamycin alleviates cisplatin-induced ototoxicity in vivo. Biochem Biophys Res Commun2014 Jun 13;448(4):443-7.
  • Wang B, Jia H, Zhang B, Wang J, Ji C, Zhu X, et al. Pre-incubation with hucMSC-exosomes prevents cisplatin-induced nephrotoxicity by activating autophagy. Stem Cell Res Ther2017 Apr 8;8(1):75.
  • Bustos-Obregón E, Esponda P. Ageing induces apoptosis and increases HSP70 Stress Protein in the epididymis of Octodon degus. 2004.

Histological evaluation of the effects of rapamycin and 3-methyladenine on cisplatin-induced epididymal injury in rats

Yıl 2021, Cilt: 46 Sayı: 3, 1184 - 1190, 30.09.2021
https://doi.org/10.17826/cumj.924352

Öz

Purpose: In this study, we aimed to determine the effects of autophagy inhibitor and activator on Cisplatin (Cis)-induced tissue damage.
Materials and Methods: A total of 24 male Wistar albino rats were divided into 4 groups including 6 rats per group in this study. Groups are as follows; Control, Cisplatin (Cis) (8 mg/kg), Rapamycin (Rapa) (2 mg/kg), 3-methyladenine (3-MA) (15 mg/kg). Rapa and 3-MA were given intraperitoneally for 15 days. Cis was administered as a single dose on the 7th day of the experimental period. At the end of the experimental procedure, epididymis tissues were extracted. Hematoxylin and eosin staining and Heat shock protein-70 (HSP70) immunohistochemistry were applied to the sections taken after histological techniques.
Results: Dispersion in the tubule basement membrane and vacuolization in the tubule was observed in the Cis group. It was also observed that some epithelial cells were more eosinophilic in the Cis group. Tissue sections of Rapa and 3-MA had a more regular appearance in terms of epithelization and tubule basement membrane. HSP70 immunoreactivity was observed in the intertubuler connective tissue of all groups.
Conclusion: The epididymis was affected by agents such as Cis in terms of the protection of semen quality and potency of spermatozoa. Rapa may be more effective than 3-MA in the epididymis against Cis toxicity.

Proje Numarası

TSA-2019-8792

Kaynakça

  • Wang H, Kumar TR. Segment- and cell-specific expression of D-type cyclins in the postnatal mouse epididymis. Gene Expr Patterns2012 Mar-Apr;12(3-4):136-44.
  • Bezerra MS, Martins ABM, Trajano FMG, Pontes THA, Gomes L, Gavioli EC, et al. Fluoxetine and sertraline effects on rat distal cauda epididymis contraction, sperm count and sperm transit time trough epididymis. Eur J Pharmacol2019 Dec 15;865:172774.
  • Reddy KP, Madhu P, Reddy PS. Protective effects of resveratrol against cisplatin-induced testicular and epididymal toxicity in rats. Food Chem Toxicol2016 May;91:65-72.
  • Jahan S, Munawar A, Razak S, Anam S, Ain QU, Ullah H, et al. Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats. BMC Urol2018 Nov 21;18(1):107.
  • Soni KK, Kim HK, Choi BR, Karna KK, You JH, Cha JS, et al. Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress. Drug Des Devel Ther2016;10:3959-68.
  • Krawczyk Z, Gogler-Pigłowska A, Sojka DR, Scieglinska D. The Role of Heat Shock Proteins in Cisplatin Resistance. Anticancer Agents Med Chem2018;18(15):2093-109.
  • Shevtsov M, Huile G, Multhoff G. Membrane heat shock protein 70: a theranostic target for cancer therapy. Philos Trans R Soc Lond B Biol Sci2018 Jan 19;373(1738).
  • Rabinowitz JD, White E. Autophagy and metabolism. Science2010 Dec 3;330(6009):1344-8.
  • Ghasemnejad-Berenji M, Ghazi-Khansari M, Yazdani I, Saravi SSS, Nobakht M, Abdollahi A, et al. Rapamycin protects testes against germ cell apoptosis and oxidative stress induced by testicular ischemia-reperfusion. Iran J Basic Med Sci2017 Aug;20(8):905-11.
  • Liu S, Huang L, Geng Y, He J, Chen X, Xu H, et al. Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats. Mol Med Rep2017 Oct;16(4):4029-37.
  • Wang X, Zhou G, Liu C, Wei R, Zhu S, Xu Y, et al. Acanthopanax versus 3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats. Mediators Inflamm2016;2016:8369704.
  • Ceylan T, Kaymak E, Cantürk Tan F, Yakan B. Research on the protective effect of caffeic acid phenethyl ester on testicular damage caused by cisplatin. Turk J Med Sci2020 Dec 17;50(8):2032-9.
  • Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol2016 May;16(5):310-5.
  • Whirledge SD, Garcia JM, Smith RG, Lamb DJ. Ghrelin partially protects against cisplatin-induced male murine gonadal toxicity in a GHSR-1a-dependent manner. Biol Reprod2015 Mar;92(3):76.
  • Erdemli EA, Ergeneci D, Atahan Ş, IŞIKAY L. Cisplatinin siçan böbrek ve testisleri üzerine etkileri. 1999.
  • Liu J, Liu Y, Habeebu SS, Klaassen CD. Metallothionein (MT)-null mice are sensitive to cisplatin-induced hepatotoxicity. Toxicol Appl Pharmacol1998 Mar;149(1):24-31.
  • Zicca A, Cafaggi S, Mariggiò MA, Vannozzi MO, Ottone M, Bocchini V, et al. Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats. Eur J Pharmacol2002 May 10;442(3):265-72.
  • Sadzuka Y, Shoji T, Takino Y. Change of lipid peroxide levels in rat tissues after cisplatin administration. Toxicol Lett1991 Jul;57(2):159-66.
  • Sainath S, Sowbhagyamma T, Madhu P, Reddy KP, Girish B, Reddy PS. Protective effect of speman on cisplatin-induced testicular and epididymal toxicity in mice. International Journal of Green Pharmacy (IJGP)2011;5(4).
  • Vernet P, Aitken R, Drevet J. Antioxidant strategies in the epididymis. Molecular and cellular endocrinology2004;216(1-2):31-9.
  • Sadeghi N, Erfani-Majd N, Tavalaee M, Tabandeh MR, Drevet JR, Nasr-Esfahani MH. Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele. Oxid Med Cell Longev2020;2020:5140383.
  • Fang B, Xiao H. Rapamycin alleviates cisplatin-induced ototoxicity in vivo. Biochem Biophys Res Commun2014 Jun 13;448(4):443-7.
  • Wang B, Jia H, Zhang B, Wang J, Ji C, Zhu X, et al. Pre-incubation with hucMSC-exosomes prevents cisplatin-induced nephrotoxicity by activating autophagy. Stem Cell Res Ther2017 Apr 8;8(1):75.
  • Bustos-Obregón E, Esponda P. Ageing induces apoptosis and increases HSP70 Stress Protein in the epididymis of Octodon degus. 2004.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma
Yazarlar

Tayfun Ceylan 0000-0002-0917-0378

Derya Karabulut 0000-0003-2067-6174

Emel Öztürk 0000-0003-0756-0329

Ali Tuğrul Akin 0000-0002-1408-8571

Emin Kaymak 0000-0002-3818-2693

Birkan Yakan 0000-0002-5456-4579

Proje Numarası TSA-2019-8792
Yayımlanma Tarihi 30 Eylül 2021
Kabul Tarihi 25 Haziran 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 46 Sayı: 3

Kaynak Göster

MLA Ceylan, Tayfun vd. “Histological Evaluation of the Effects of Rapamycin and 3-Methyladenine on Cisplatin-Induced Epididymal Injury in Rats”. Cukurova Medical Journal, c. 46, sy. 3, 2021, ss. 1184-90, doi:10.17826/cumj.924352.