Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways

Özbal, Seda; Koçak, Ayşe; ERSAN, Sibel; arslan, sevki; DUBOVA, Aslı; TATLI, Merve; ural, cemre; ÇAVDAR, Caner; Cavdar, Zahide

doi:10.1515/tjb-2018-0155

Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways

Zahide ÇAVDAR, (Department of Molecular Medicine, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey)

Cemre URAL, (Department of Molecular Medicine, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey,)

Ayşe KOÇAK, (Department of Molecular Medicine, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey,)

Şevki ARSLAN, (Department of Biology, Faculty of Science, Pamukkale University, Denizli, Turkey)

Sibel ERSAN, (Izmir Tepecik Research and Training Hospital, Department of Nephrology, Izmir, Turkey)

Seda ÖZBAL, (Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey)

Merve TATLI, (Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey)

Aslı DUBOVA, (Department of Laboratory Animal Science, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey)

Caner ÇAVDAR (Department of Nephrology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey)

Türk Biyokimya Dergisi

5 1

Yıl: 2019 Cilt: 44 Sayı: 4 Sayfa Aralığı: 452 - 461 Metin Dili: İngilizce DOI: 10.1515/tjb-2018-0155 İndeks Tarihi: 05-06-2020

Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways

Öz:

Objective: This study aimed to investigate the renoprotec- tive effects of paricalcitol, a synhetic vitamin D analog, through its possible roles on p38 MAPK and PI3K/Akt signaling pathways to prevent oxidative stress, inflamma- tion and apoptosis during renal I/R.Materials and methods: Total 20 kidney tissues of sham (n  6), subjected to renal I/R bilaterally for 45 min ischemia followed by 24 h reperfusion (n  7) and parical- citol (0.3 g/kg, ip) pretreated Wistar albino rats (n  7) were used in this study. Interstitial inflammation and active caspase-3 expression were evaluated histologically. TNF-, IL-1, kidney injury molecule-1 (KIM-1), MDA and SOD activity in kidneys were analysed biochemically. Fur- thermore, activation of p38 MAPK, PI3K/Akt signaling pathways and NFB p65 were evaluated by western blot. Results: Paricalcitol pretreatment significantly reduced interstitial inflammation during renal I/R, which was consistent with decreased tumor TNF-, IL-1, active caspase-3 and KIM-1 expression. Paricalcitol also reduced MDA level and attenuated the reduction of SOD activity in the kidney during I/R. Moreover, paricalcitol could suppress the p38 MAPK and NFB p65, and also activate PI3K/Akt signaling pathway during renal I/R. Conclusion: All these findings indicate that paricalcitol may be an effective practical strategy to prevent renal I/R injury.

Anahtar Kelime:

Parikalsitol renal iskemi/reperfüzyon hasarını p38 MAPK aktivasyonunu inhibe ederek ve PI3K/Akt’ı aktive ederek azaltır

Öz:

Amaç: Bu çalışmanın amacı vitamin D’nin bir sentetik analoğu olan parikalsitol’ün renal iskemi/reperfüzyon (I/R) süresince oksidatif stres, inflamasyon ve apoptozise karşı renoprotektif etkisini p38 MAPK ve PI3K/Akt sinyal ileti yolakları üzerine olası rolleri ile araştırmaktır. Gereç ve yöntem: Sham (n  6) grubu, bilateral renal iskemi/reperfüzyon (I/R) (45 dak iskemi, 24 saat reperfüz- yon) (n  7) ve renal I/R’den önce parikalsitol (0.3 g/kg, i.p) (n  7) uygulanan Wistar albino sıçanlardan alınan toplam 20 böbrek dokusu kullanıldı. İnterstisyel inflamasyon ve aktif kaspaz-3 histolojik analizler ile değerlendirildi. Böbrek dokusunda TNF-, IL-1, böbrek hasar molekülü-1 (KIM-1), MDA ve SOD biyokimyasal olarak analiz edildi. p38 MAPK, PI3K/Akt sinyal yolaklarının aktivasyonu ve NFB p65 Western blot ile değerlendirildi. Bulgular: Parikalsitol, renal I/R süresince oluşan interstis- yel inflamasyonu anlamlı olarak azalttı. Bununla ilişkili olarak renal I/R süresince artan TNF-, IL-1, aktif kaspaz-3 ve KIM-1 parikalsitol ile anlamlı olarak azaldı. Parikalsitol ile aynı zamanda renal I/R süresince böbrek dokusunda artan MDA seviyesi anlamlı olarak azalırken, SOD aktivite düzeyi ise anlamlı olarak arttı. Ayrıca parikalsitolün renal I/R süresince artan p38 MAPK aktivasyonunu ve NFB p65 protein ifadesini baskılayabildiği ve PI3K/Akt sinyal ileti yolağını da aktive edebildiği saptandı. Sonuç: Tüm bu bulgular parikalsitol’ün renal I/R hasarına karşı geliştirilen stratejilerde aday olabileceğine işaret etmektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Cavdar Z, ural c, Koçak A, arslan s, ERSAN S, Özbal S, TATLI M, DUBOVA A, ÇAVDAR C (2019). Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. , 452 - 461. 10.1515/tjb-2018-0155
Chicago	Cavdar Zahide,ural cemre,Koçak Ayşe,arslan sevki,ERSAN Sibel,Özbal Seda,TATLI Merve,DUBOVA Aslı,ÇAVDAR Caner Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. (2019): 452 - 461. 10.1515/tjb-2018-0155
MLA	Cavdar Zahide,ural cemre,Koçak Ayşe,arslan sevki,ERSAN Sibel,Özbal Seda,TATLI Merve,DUBOVA Aslı,ÇAVDAR Caner Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. , 2019, ss.452 - 461. 10.1515/tjb-2018-0155
AMA	Cavdar Z,ural c,Koçak A,arslan s,ERSAN S,Özbal S,TATLI M,DUBOVA A,ÇAVDAR C Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. . 2019; 452 - 461. 10.1515/tjb-2018-0155
Vancouver	Cavdar Z,ural c,Koçak A,arslan s,ERSAN S,Özbal S,TATLI M,DUBOVA A,ÇAVDAR C Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. . 2019; 452 - 461. 10.1515/tjb-2018-0155
IEEE	Cavdar Z,ural c,Koçak A,arslan s,ERSAN S,Özbal S,TATLI M,DUBOVA A,ÇAVDAR C "Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways." , ss.452 - 461, 2019. 10.1515/tjb-2018-0155
ISNAD	Cavdar, Zahide vd. "Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways". (2019), 452-461. https://doi.org/10.1515/tjb-2018-0155

APA	Cavdar Z, ural c, Koçak A, arslan s, ERSAN S, Özbal S, TATLI M, DUBOVA A, ÇAVDAR C (2019). Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. Türk Biyokimya Dergisi, 44(4), 452 - 461. 10.1515/tjb-2018-0155
Chicago	Cavdar Zahide,ural cemre,Koçak Ayşe,arslan sevki,ERSAN Sibel,Özbal Seda,TATLI Merve,DUBOVA Aslı,ÇAVDAR Caner Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. Türk Biyokimya Dergisi 44, no.4 (2019): 452 - 461. 10.1515/tjb-2018-0155
MLA	Cavdar Zahide,ural cemre,Koçak Ayşe,arslan sevki,ERSAN Sibel,Özbal Seda,TATLI Merve,DUBOVA Aslı,ÇAVDAR Caner Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. Türk Biyokimya Dergisi, vol.44, no.4, 2019, ss.452 - 461. 10.1515/tjb-2018-0155
AMA	Cavdar Z,ural c,Koçak A,arslan s,ERSAN S,Özbal S,TATLI M,DUBOVA A,ÇAVDAR C Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. Türk Biyokimya Dergisi. 2019; 44(4): 452 - 461. 10.1515/tjb-2018-0155
Vancouver	Cavdar Z,ural c,Koçak A,arslan s,ERSAN S,Özbal S,TATLI M,DUBOVA A,ÇAVDAR C Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways. Türk Biyokimya Dergisi. 2019; 44(4): 452 - 461. 10.1515/tjb-2018-0155
IEEE	Cavdar Z,ural c,Koçak A,arslan s,ERSAN S,Özbal S,TATLI M,DUBOVA A,ÇAVDAR C "Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways." Türk Biyokimya Dergisi, 44, ss.452 - 461, 2019. 10.1515/tjb-2018-0155
ISNAD	Cavdar, Zahide vd. "Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways". Türk Biyokimya Dergisi 44/4 (2019), 452-461. https://doi.org/10.1515/tjb-2018-0155