Nicotinamide mononucleotide attenuates doxorubicin-induced cardiotoxicity by reducing oxidative stress, inflammation and apoptosis in rats

Wan, Yixuan; He, Bo; Zhu, Dongyong; Wang, Lei; Huang, Ruijue; Zhu, Jing; Wang, Chunhua

doi:10.1016/j.abb.2021.109050

Cited by 16 publications

(11 citation statements)

References 52 publications

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“…Overall, these results indicate promising cardioprotective effects of NMN against Doxo toxicity. These findings are consistent with previous work suggesting that NMN could protect cardiomyocytes from Doxo-induced toxicity and further support the cardioprotective potential of NMN already demonstrated in various cardiac conditions such as heart failure, cardiac fibrosis and cardiotoxicity [24,63,[66][67][68].…”

Section: Discussionsupporting

confidence: 92%

“…Despite a significant decline in heart rate, we did not detect any significant changes in EF or FS at 53 days (Figure 3E) as well as at 30 days post Doxo treatment (data not shown), suggesting that this regimen of Doxo could potentially induce more pronounced cardiac defects at a later time point or in different experimental models. Indeed, in Wistar rats, chronic injections of Doxo at cumulative doses of 12 and 15 mg/kg resulted in significant cardiac tissue damage that was significantly attenuated by NMN [68] and even totally prevented by the combination of NMN with troxerutin (vitamin P4) [24]. On the other hand, our data show that the physical capacity measured by the treadmill exhaustion and rotarod tests was significantly reduced by Doxo (Figure 5), indicating skeletal muscle weakness.…”

Section: Discussionmentioning

confidence: 69%

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

Margier¹,

Kuehnemann

Hulo³

et al. 2022

Cells

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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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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 69%

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

Margier¹,

Kuehnemann

Hulo³

et al. 2022

Cells

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“…NMN has been found to inhibit ROS production and oxidative stress in the heart and brain [ 21 , 22 , 40 ]. However, to the best of our knowledge, this is the first report to evaluate the antioxidant effect of NMN in tendons.…”

Section: Discussionmentioning

confidence: 99%

“…However, to the best of our knowledge, this is the first report to evaluate the antioxidant effect of NMN in tendons. The antioxidant function of NMN has been linked to maintenance of mitochondrial homeostasis and increased levels of antioxidants [ 22 , 40 , 41 ]. Furthermore, SIRT1, which is stimulated by NMN, has been associated with suppressing oxidative stress by downregulating NOX production [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant effect of nicotinamide mononucleotide in tendinopathy

Yamaura

Mifune

Inui

et al. 2022

BMC Musculoskelet Disord

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Background A link between tendinopathy and oxidative stress has been recently reported. Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide, which plays an important role in cell redox homeostasis. The aim of this study was to evaluate the antioxidant effect of NMN on tendinopathy in vitro and in vivo. Methods Tenocytes from healthy Sprague-Dawley rats were cultured in regular glucose (RG) and high-glucose (HG) conditions with or without NMN, and were divided into four groups: RG NMN(−), RG NMN(+), HG NMN(−), and HG NMN(+). Cell viability, reactive oxygen species (ROS) accumulation, apoptotic rate, and mRNA expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)1, NOX4, interleukin (IL)6, sirtuin (SIRT)1, and SIRT6 were investigated. In addition, rats with collagenase-induced tendinopathy were treated with or without NMN. Immunostaining of NOX1 and NOX4; mRNA expression of SIRT1, SIRT6, and IL6; and superoxide dismutase (SOD) activity measurements in the Achilles tendon were performed. Results NMN increased the expression of SIRT1 and SIRT6 in rat tenocytes, but decreased the levels of NOX1, NOX4, IL6, ROS, and apoptosis. In Achilles tendons with collagenase-induced tendinopathy, NMN increased the mRNA expression of SIRT1 and SIRT6, as well as SOD activity; while suppressing protein expression of NOX1 and NOX4, and mRNA expression of IL6. Conclusion The in vitro and in vivo results of this study show that NMN exerts an antioxidant effect on tendinopathy by promoting the expression of SIRT while inhibiting that of NOX.

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“…These decreases were thought to be due to tyrosol's antioxidant effect on heart tissue, which inhibits lipid peroxidation. Doxorubicin administration causes various histopathological changes, such as cardiomyocyte vacuolization in heart tissue, increased extracellular fibrosis, muscle fiber disorder, myofibril loss, enlarged and abnormally shaped mitochondria, inflammatory cell infiltration, increased cell death, cardiomyocyte apoptosis, edema of myocardial cells, myocardial tissue hemorrhage, blood vessel occlusion, pycnotic nuclei and necrosis (Kumrala et al 2015, Haybara et al 2019, Ma et al 2019, Öner et al 2019, Liao et al 2020, Sandamali et al 2020, Tiana et al 2020, Yuan et al 2020, Ahmed et al 2021, Wan et al 2021. When the heart tissue samples from the control and tyrosol groups were examined, the cardiac muscle cells were found to have normal histological features.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the efficacy of tyrosol on doxorubicin-induced acute cardiotoxicity in rats

Cellat¹,

Etyemez²

2023

EurasianJVetSci

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Amaç: Çalışmada, doksorubisin ile oluşturulan kardiyotoksisite üzerine tirozolün etkinliğinin araştırılması amaçlandı. Gereç ve Yöntem: Ratlar 4 gruba ayrıldı ve her grupta 8 rat yer aldı. Grup 1 ve grup 2’ye 1 ml serum fizyolojik, grup 3 ve grup 4’e ise 20 mg/kg dozda tirozol uygulaması yapıldı. Serum fizyolojik ve tirozol uygulamalarında oral gavaj yöntemi kullanıldı. Ayrıca grup 2 ve grup 4’e denemenin 12. günü 15 mg/kg dozda ve tek doz intraperitoneal doksorubisin uygulaması yapıldı. Denemenin 14. gününde anestezi altındaki ratlardan serum ve doku örnekleri alındı ve daha sonra ötanazi edildi. Serum kreatin kinaz MB ve kreatin kinaz aktiviteleri analiz edildi. Kalp dokuları çıkarıldı ve bu dokularda histopatolojik ve oksidatif stres parametrelerine yönelik analizler yapıldı. Kalp dokusu malondialdehit ve redükte glutatyon düzeyleri ile katalaz ve glutatyon peroksidaz enzim aktiviteleri spektrofotometrik olarak belirlendi. Bulgular: Tirozol ön tedavisinin doksorubisinin neden olduğu kalp dokusu malondialdehit düzeyindeki artışı (p<0.05), redükte glutatyon düzeyi ve glutatyon peroksidaz enzim aktivitesindeki azalmaları engellediği ve doksorubisinin kalp dokusunda meydana getirdiği oksidatif stresi baskıladığı görüldü. Kalp dokusu katalaz enzim aktiviteleri açısından gruplar arasında farklılık gözlenmedi. Kalpteki oksidatif hasarın azalmasına bağlı olarak serum kreatin kinaz MB ve kreatin kinaz aktivitelerinin önemli oranda azaldığı (p<0.05) tespit edildi. Ayrıca tirozol ön tedavisinin doksorubisinin kalp dokusunda meydana getirdiği histopatolojik lezyonları engellediği belirlendi. Öneri: Tirozol uygulamasının doksorubisinin neden olduğu kardiyotoksisiteyi azaltabileceği düşünülmektedir.

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Nicotinamide mononucleotide attenuates doxorubicin-induced cardiotoxicity by reducing oxidative stress, inflammation and apoptosis in rats

Cited by 16 publications

References 52 publications

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

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

Antioxidant effect of nicotinamide mononucleotide in tendinopathy

Investigation of the efficacy of tyrosol on doxorubicin-induced acute cardiotoxicity in rats

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