Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats

Abstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized grou...

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Main Authors: Rasha Mohamed Sabry Mohamed Mohamed, Shimaa Mostafa Elshazly, Nevertyty Mohamed Mahmoud
Format: Article
Language:English
Published: Universidade de São Paulo 2023-01-01
Series:Brazilian Journal of Pharmaceutical Sciences
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502022000100845&tlng=en
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author Rasha Mohamed Sabry Mohamed Mohamed
Shimaa Mostafa Elshazly
Nevertyty Mohamed Mahmoud
author_facet Rasha Mohamed Sabry Mohamed Mohamed
Shimaa Mostafa Elshazly
Nevertyty Mohamed Mahmoud
author_sort Rasha Mohamed Sabry Mohamed Mohamed
collection DOAJ
description Abstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized group. Amlexanox (25 mg/kg/day, i.p.) administration was started just after surgery and continued for 10 weeks. After treatment, kidney function (serum creatinine and urea) and blood pressure (systolic and diastolic) were measured. Heart weight (normalized to tibial length) and fibrosis area percentage were measured. Serum brain natriuretic peptide (BNP, heart failure marker) and cardiac levels of β1-adrenergic receptor (β1AR), β-arrestin-2, phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol (DAG), pS473 Akt (a survival marker), and caspase-3 activity (an apoptosis marker) were also measured. The 5/6 nephrectomy caused renal impairment, cardiac fibrosis, apoptosis, and heart failure indicated by down- regulation of cardiac β1AR down-stream signals compared with those in the sham group. Interestingly, amlexanox significantly reduced all cardiopathological changes induced after 10 weeks of 5/6 nephrectomy. Amlexanox showed potent cardiac antifibrotic and antiapoptotic effects in 5/6 nephrectomized rats, which were associated with reduced heart failure. To our knowledge, this is the first study that addresses the potent in vivo cardioprotective effects of amlexanox.
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spelling doaj.art-2398d402c8264e559c6b6338a269f0f42023-01-10T07:34:31ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902023-01-015810.1590/s2175-97902022e20978Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized RatsRasha Mohamed Sabry Mohamed Mohamedhttps://orcid.org/0000-0002-4173-4399Shimaa Mostafa ElshazlyNevertyty Mohamed MahmoudAbstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized group. Amlexanox (25 mg/kg/day, i.p.) administration was started just after surgery and continued for 10 weeks. After treatment, kidney function (serum creatinine and urea) and blood pressure (systolic and diastolic) were measured. Heart weight (normalized to tibial length) and fibrosis area percentage were measured. Serum brain natriuretic peptide (BNP, heart failure marker) and cardiac levels of β1-adrenergic receptor (β1AR), β-arrestin-2, phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol (DAG), pS473 Akt (a survival marker), and caspase-3 activity (an apoptosis marker) were also measured. The 5/6 nephrectomy caused renal impairment, cardiac fibrosis, apoptosis, and heart failure indicated by down- regulation of cardiac β1AR down-stream signals compared with those in the sham group. Interestingly, amlexanox significantly reduced all cardiopathological changes induced after 10 weeks of 5/6 nephrectomy. Amlexanox showed potent cardiac antifibrotic and antiapoptotic effects in 5/6 nephrectomized rats, which were associated with reduced heart failure. To our knowledge, this is the first study that addresses the potent in vivo cardioprotective effects of amlexanox.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502022000100845&tlng=enAmlexanoxCardiorenal syndromeβ-Arrestin-2
spellingShingle Rasha Mohamed Sabry Mohamed Mohamed
Shimaa Mostafa Elshazly
Nevertyty Mohamed Mahmoud
Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats
Brazilian Journal of Pharmaceutical Sciences
Amlexanox
Cardiorenal syndrome
β-Arrestin-2
title Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats
title_full Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats
title_fullStr Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats
title_full_unstemmed Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats
title_short Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats
title_sort amlexanox exhibits cardioprotective effects in 5 6 nephrectomized rats
topic Amlexanox
Cardiorenal syndrome
β-Arrestin-2
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502022000100845&tlng=en
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AT shimaamostafaelshazly amlexanoxexhibitscardioprotectiveeffectsin56nephrectomizedrats
AT nevertytymohamedmahmoud amlexanoxexhibitscardioprotectiveeffectsin56nephrectomizedrats