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Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats.
Mohamad, Hoda E; Asker, Mervat E; Shaheen, Mohamed A; Baraka, Nourhan M; Fantoukh, Omer I; Alqahtani, Abdulaziz; Salama, Alaa E; Mahmoud, Yasmin K.
Afiliação
  • Mohamad HE; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
  • Asker ME; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
  • Shaheen MA; Department of Histology & Cell Biology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
  • Baraka NM; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
  • Fantoukh OI; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Alqahtani A; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Salama AE; Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
  • Mahmoud YK; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Life (Basel) ; 13(2)2023 Jan 22.
Article em En | MEDLINE | ID: mdl-36836664
ABSTRACT
Sunitinib has been associated with several cardiotoxic effects such as cardiac fibrosis. The present study was designed to explore the role of interleukin (IL)-17 in sunitinib-induced myocardial fibrosis (MF) in rats and whether its neutralization and/or administration of black garlic (BG), a form of fermented raw garlic (Allium sativum L.), could extenuate this adverse effect. Male Wistar albino rats received sunitinib (25 mg/kg three times a week, orally) and were co-treated with secukinumab (3 mg/kg, subcutaneously, three times total) and/or BG (300 mg/kg/day, orally) for four weeks. Administration of sunitinib induced significant increase in cardiac index, cardiac inflammatory markers, and cardiac dysfunction that were ameliorated by both secukinumab and BG, and to a preferable extent, with the combined treatment. Histological examination revealed disruption in the myocardial architecture and interstitial fibrosis in cardiac sections of the sunitinib group, which were reversed by both secukinumab and BG treatments. Both drugs and their co-administration restored normal cardiac functions, downregulated cardiac inflammatory cytokines, mainly IL-17 and NF-κB, along with increasing the MMP1/TIMP1 ratio. Additionally, they attenuated sunitinib-induced upregulation of the OPG/RANK/RANKL axis. These findings highlight another new mechanism through which sunitinib can induce interstitial MF. The current results propose that neutralizing IL-17 by secukinumab and/or supplementation with BG can be a promising therapeutic approach for ameliorating sunitinib-induced MF.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Life (Basel) Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Life (Basel) Ano de publicação: 2023 Tipo de documento: Article