Combination of nicotinamide mononucleotide and troxerutin induces full protection against doxorubicin-induced cardiotoxicity by modulating mitochondrial biogenesis and inflammatory response.
Cardiotoxicity
Doxorubicin
Mitochondrial biogenesis
Mitochondrial function
Nicotinamide mononucleotide
Troxerutin.
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
22
12
2021
accepted:
16
03
2022
revised:
05
03
2022
pubmed:
18
7
2022
medline:
14
9
2022
entrez:
17
7
2022
Statut:
ppublish
Résumé
Clinical application of doxorubicin (DOX) is restricted due to its cardiotoxicity, reinforcing the significance of exploring new strategies to counteract DOX-induced cardiotoxicity. The present work aimed to investigate the ameliorative impact of combination therapy with nicotinamide mononucleotide (NMN) and troxerutin (TXR) on DOX-induced cardiotoxicity, with mitochondrial function/biogenesis and inflammatory response approach. Male Wistar rats (n = 30, 250-300 g) were divided into groups with/without DOX and/or NMN and TXR, alone or in combination. Rats underwent 6 consecutive intraperitoneal injections of DOX (cumulative dose: 12 mg/kg). NMN (100 mg/kg/day; intraperitoneally) and/or TXR (150 mg/kg/day; orally) were administered for 28 days before DOX challenge. Seven days following the last injection of DOX, evaluation of cardiac histopathological changes, BNP and LDH levels, mitochondrial function (membrane potential, ROS generation, and ATP levels), expression of proteins involved in mitochondrial biogenesis (PGC-1α, NRF1, and TFAM), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) was performed. Combination of NMN and TXR significantly decreased the severity of histopathological damages, and BNP and LDH levels (P < 0.01 to P < 0.001). It also restored mitochondrial functional endpoints, and expression of proteins involved in mitochondrial biogenesis (P < 0.05 to P < 0.001), and decreased inflammatory cytokines (P < 0.01 to P < 0.001). The positive impacts of this combination therapy were more potent as compared to monotherapies. These findings shed new light on the understanding of additive properties of NMN/TXR combination therapy in protecting against DOX-induced cardiotoxicity. The cardioprotective effect of this combination therapy may be mediated in part through the restoration of mitochondrial function/biogenesis associated with the PGC-1α/NRF1/TFAM pathway, and suppression of inflammatory response.
Sections du résumé
BACKGROUND
BACKGROUND
Clinical application of doxorubicin (DOX) is restricted due to its cardiotoxicity, reinforcing the significance of exploring new strategies to counteract DOX-induced cardiotoxicity. The present work aimed to investigate the ameliorative impact of combination therapy with nicotinamide mononucleotide (NMN) and troxerutin (TXR) on DOX-induced cardiotoxicity, with mitochondrial function/biogenesis and inflammatory response approach.
METHODS
METHODS
Male Wistar rats (n = 30, 250-300 g) were divided into groups with/without DOX and/or NMN and TXR, alone or in combination. Rats underwent 6 consecutive intraperitoneal injections of DOX (cumulative dose: 12 mg/kg). NMN (100 mg/kg/day; intraperitoneally) and/or TXR (150 mg/kg/day; orally) were administered for 28 days before DOX challenge. Seven days following the last injection of DOX, evaluation of cardiac histopathological changes, BNP and LDH levels, mitochondrial function (membrane potential, ROS generation, and ATP levels), expression of proteins involved in mitochondrial biogenesis (PGC-1α, NRF1, and TFAM), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) was performed.
RESULTS
RESULTS
Combination of NMN and TXR significantly decreased the severity of histopathological damages, and BNP and LDH levels (P < 0.01 to P < 0.001). It also restored mitochondrial functional endpoints, and expression of proteins involved in mitochondrial biogenesis (P < 0.05 to P < 0.001), and decreased inflammatory cytokines (P < 0.01 to P < 0.001). The positive impacts of this combination therapy were more potent as compared to monotherapies.
CONCLUSIONS
CONCLUSIONS
These findings shed new light on the understanding of additive properties of NMN/TXR combination therapy in protecting against DOX-induced cardiotoxicity. The cardioprotective effect of this combination therapy may be mediated in part through the restoration of mitochondrial function/biogenesis associated with the PGC-1α/NRF1/TFAM pathway, and suppression of inflammatory response.
Identifiants
pubmed: 35842854
doi: 10.1007/s11033-022-07390-5
pii: 10.1007/s11033-022-07390-5
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Cytokines
0
Hydroxyethylrutoside
0
Nicotinamide Mononucleotide
1094-61-7
troxerutin
7Y4N11PXO8
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8209-8218Subventions
Organisme : Tabriz University of Medical Sciences
ID : Tabriz University of Medical Sciences
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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