sdü tıp fak derg

Medical Journal of Süleyman Demirel University

2602-2109

Süleyman Demirel Üniversitesi

10.17343/sdutfd.1198304

Clinical Sciences

Klinik Tıp Bilimleri

INVESTIGATION OF ANTIOXIDANT AND ANTIAPOPTOTIC EFFECTS OF LERCANIDIPINE IN DOXORUBICIN-INDUCED KIDNEY DAMAGE VIA BCL-2/BAX/SIT C/CAS-3 SIGNALING PATHWAY

DOKSORUBİSİN İLE OLUŞTURULAN BÖBREK HASARINDA LERKANİDİPİNİN ANTİOKSİDAN VE ANTİAPOPTOTİK ETKİLERİNİN BCL-2/BAX/SİT C/ CAS-3 YOLAĞI ÜZERİNDEN ARAŞTIRILMASI

https://orcid.org/0000-0003-3739-9580

İlhan

İlter

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0002-1545-035X

Aşcı

Halil

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0003-3875-9365

Sevük

Mehmer Abdulkadir

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0002-3850-0137

İmeci

Orhan Berk

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0002-3614-7798

Milletsever

Adem

MEHMET AKİF ERSOY ÜNİVERSİTESİ

https://orcid.org/0000-0001-7935-5004

Sancer

Okan

SÜLEYMAN DEMİREL ÜNİVERSİTESİ

12 27 2022

29 4 671 679 11 02 2022 12 06 2022

1994

Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

ObjectiveDoxorubicin (Dox) is an antineoplastic drug used inchemotherapy. Nephrotoxicity is one of the importantside effects that limit the use of Dox. It is known thatlercanidipine (Ler), a calcium channel blocker, has antioxidantand antiapoptotic properties. In our study, weaimed to evaluate the effects of Lercanidipine (Ler) onoxidative stress and apoptosis in Dox-induced kidneydamage in rats.Material and MethodTwenty-four adult male rats were divided into 3 equalgroups: control, Dox (20 mg/kg Dox intraperitoneallyonce on day 8) and Dox+Ler (20 mg/kg Dox intraperitoneallyonce on day 8, 2 mg/kg Ler by oral gavageevery day for 10 days). At the end of the study, bloodurea nitrogen (BUN) and creatinine levels were measuredfrom the serum of rats. Also, total oxidant status(TOS), total antioxidant status (TAS) and superoxidedismutase (SOD) enzyme activity determinedfrom kidney tissues. In addition, Bcl-2-associated Xprotein (Bax), B-cell-lymphoma-2 (Bcl-2) cytochromec (sit c) and caspase-3 (Cas-3) mRNA expression levelsin kidney tissue were analyzed by quantitativereal time polymerase chain reaction method. Also,histopathological changes were examined by hematoxylin-eosin staining.ResultsIn our study, Dox administration elevated BUN, creatinine,TOS and oxidative stress index, while decreasingSOD activity and TAS levels. In addition, whilethe expression of proapoptotic markers (Bax, sit c andCas-3) increased in the Dox group, the expression ofBcl-2, an antiapoptotic factor, decreased. In histologicalexaminations, findings indicating kidney damagedue to Dox exposure were observed. But, the Ler administrationshowed protective effects by limiting allthe changes related to Dox in the kidney.ConclusionOur study shows that Ler may be a potential candidatedrug for preventing Dox-induced kidney damageby showing antioxidant and antiapoptotic properties.

AmaçDoksorubisin (Dox) kemoterapide kullanılan antineoplastikbir ilaçtır. Nefrotoksisite, Dox’un kullanımınıkısıtlayan önemli yan etkilerden biridir. Bir kalsiyumkanal blokeri olan lerkanidipinin (Ler) antioksidan veantiapoptotik özellik gösterdiği bilinmektedir. Çalışmamızda,sıçanlarda oluşturulan Dox uygulaması iletetiklenen böbrek hasarında Ler’in oksidatif stres veapoptoz üzerine etkilerini değerlendirmeyi amaçladık.Gereç ve YöntemYirmi dört adet erişkin erkek sıçan; kontrol, Dox (8.günde bir kez intraperitoneal 20 mg/kg) ve Dox+Ler(8. günde bir kez intraperitoneal 20 mg/kg Dox, hergün oral gavaj ile 2 mg/kg Ler 10 gün boyunca) şeklinde3 eşit gruba ayrılmıştır. Çalışma sonunda sakrifiyeedilen sıçanların kanlarından kan üre azotu (BUN) vekreatinin ile alınan böbrek dokusundan total oksidanseviyesi (TOS), total antioksidan seviyesi (TAS) vesüperoksid dismutaz (SOD) enzim aktivitesi ölçülmüştür.Ayrıca, böbrek dokusunda Bcl-2-ilişkili X proteini(Bax), B hücreli lenfoma-2 (Bcl-2), sitokrom c (sitc) ve kaspaz-3 (Cas-3) mRNA ekspresyon düzeylerikantitatif gerçek zamanlı polimeraz zincir reaksiyonuyöntemiyle ölçülmüştür. Ek olarak hematoksilen-eozinboyama ile böbrekteki histopatolojik değişimlerincelenmiştir.BulgularÇalışmamızda, Dox uygulaması BUN, kreatinin, TOSve oksidatif stres indeks seviyelerini yükseltirken,SOD aktivitesi ve TAS seviyelerini azaltmıştır. AyrıcaDox grubunda proapoptotik belirteçlerin (Bax, sit c veCas-3) ekspresyonu artarken antiapoptotik bir faktörolan Bcl-2’nin ekspresyonu azalmıştır. Histolojik incelemelerdeise Dox’a bağlı böbrek hasarını gösterenbulgular gözlenmiştir. Ler uygulaması, böbrekteDox’a bağlı tüm değişiklikleri sınırlayarak koruyucuetkiler göstermiştir.SonuçÇalışmamız Ler’in antioksidan ve antiapoptotik özelliklergöstererek Dox’un neden olduğu böbrek hasarınıönlemede potansiyel bir aday olabileceğini göstermektedir.

Apoptoz Doksorubisin Lerkanidipin Oksidatif stres

Apoptosis Doxorubicin Lercanidipine Oxidative stress

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