Nicotinamide Mononucleotide Administration Prevents Doxorubicin-Induced Cardiotoxicity and Loss in Physical Activity in Mice

Doxorubicin (Doxo) is a widely used antineoplastic drug with limited clinical application due to its deleterious dose-related side effects. We investigated whether nicotinamide mononucleotide (NMN) could protect against Doxo-induced cardiotoxicity and physical dysfunction in vivo. To assess the shor...

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Veröffentlicht in:Cells (Basel, Switzerland) Jg. 12; H. 1; S. 108
Hauptverfasser: Margier, Marielle, Kuehnemann, Chisaka, Hulo, Nicolas, Morales, Jazmin, Ashok Kumaar, Prasanna Vadhana, Cros, Cecile, Cannelle, Helene, Charmetant, Julie, Verdin, Eric, Canault, Matthias, Grozio, Alessia
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 27.12.2022
MDPI
Schlagworte:
Age
Aging
Animal cognition
Animals
Apoptosis
Cancer therapies
Cardiotoxicity
Cardiotoxicity - prevention & control
Causes of
Dosage and administration
Doxorubicin
Doxorubicin - toxicity
Drinking water
Drug dosages
Exercise
Health aspects
Heart
Heart diseases
Humidity
Ischemia
Metabolites
Mice
Mitochondria
Musculoskeletal system
NAD
Niacinamide
Nicotinamide
nicotinamide mononucleotide
Nicotinamide Mononucleotide - pharmacology
Oxidative stress
Physical activity
physical activity impairment
Prevention
Promyeloid leukemia
Senescence
Skeletal muscle
Toxicity
Transcriptomics
Tumors
France
United States > US
NAD
cardiotoxicity
inflammation
physical activity impairment
mitochondrial functions
doxorubicin
p53-mediated pathways
nicotinamide mononucleotide
oxidative stress
ISSN:2073-4409, 2073-4409
Online-Zugang:Volltext
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Zusammenfassung:Doxorubicin (Doxo) is a widely used antineoplastic drug with limited clinical application due to its deleterious dose-related side effects. We investigated whether nicotinamide mononucleotide (NMN) could protect against Doxo-induced cardiotoxicity and physical dysfunction in vivo. To assess the short- and long-term toxicity, two Doxo regimens were tested, acute and chronic. In the acute study, C57BL6/J (B6) mice were injected intraperitoneally (i.p.) once with Doxo (20 mg/kg) and NMN (180 mg/kg/day, i.p.) was administered daily for five days before and after the Doxo injection. In the chronic study, B6 mice received a cumulative dose of 20 mg/kg Doxo administered in fractionated doses for five days. NMN (500 mg/kg/day) was supplied in the mice’s drinking water beginning five days before the first injection of Doxo and continuing for 60 days after. We found that NMN significantly increased tissue levels of NAD+ and its metabolites and improved survival and bodyweight loss in both experimental models. In addition, NMN protected against Doxo-induced cardiotoxicity and loss of physical function in acute and chronic studies, respectively. In the heart, NMN prevented Doxo-induced transcriptomic changes related to mitochondrial function, apoptosis, oxidative stress, inflammation and p53, and promyelocytic leukemia nuclear body pathways. Overall, our results suggest that NMN could prevent Doxo-induced toxicity in heart and skeletal muscle.
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These authors contributed equally to this work.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells12010108