We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Sacubitril/valsartan cardioprotective effect against cisplatin-induced cardiotoxicity via modulation of VEGF/eNOS and TLR4/TNFα/IL6 signalling pathways.
- Authors
Mahmoud Refaie, Marwa Monier; Ahmed Rifaai, Rehab; Bayoumi, Asmaa M A; Shehata, Sayed
- Abstract
Objectives: Drug-induced cardiac injury is a potentially preventable cause of heart failure. Cisplatin (CIS) is a widely used chemotherapeutic agent complicated with cardiotoxicity that limits its clinical application so we aimed to evaluate the suspected cardioprotective effect of sacubitril/valsartan (Sac/Val) against CIS cardiotoxic injury. Methods: Forty male rats of Wistar albino species were divided into four groups. group I received the vehicle; group II was given the vehicle plus CIS (10 mg/kg) single i.p. on fifth day; group III was given Sac/Val (30 mg/kg/d) orally for 7 days plus CIS (10 mg/kg) single i.p. on fif5th day; group IV was given the same as group III plus nitro-ω-L-arginine (L-NNA) (25 mg/kg/d) orally for 7 days. Key findings: CIS-induced cardiotoxicity and L-NNA co-administered group showed significant increases in cardiac enzymes, toxic histopathological features, elevated heart weights, angiotensin II (Ang II), neprilysin, malondialdehyde (MDA), inflammatory mediators, blood pressure (BP) and caspase 3 expressions, but there are significant decreases in the antioxidant parameters, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). However, the co-administration of Sac/Val could ameliorate these changes of CIS. Conclusion: Sac/Val has an important cardioprotective effect against CIS cardiotoxicity with the involvement of eNOS. Graphical Abstract
- Subjects
DOXORUBICIN; CELLULAR signal transduction; CARDIOTOXICITY; VASCULAR endothelial growth factors; NITRIC-oxide synthases; ENTRESTO; NEPRILYSIN
- Publication
Journal of Pharmacy & Pharmacology, 2023, Vol 75, Issue 9, p1237
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1093/jpp/rgad049