Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease
Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney...
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MDPI AG
2021-01-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/1/50 |
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| author | Satoshi Kumakura Emiko Sato Akiyo Sekimoto Yamato Hashizume Shu Yamakage Mariko Miyazaki Sadayoshi Ito Hideo Harigae Nobuyuki Takahashi |
| author_facet | Satoshi Kumakura Emiko Sato Akiyo Sekimoto Yamato Hashizume Shu Yamakage Mariko Miyazaki Sadayoshi Ito Hideo Harigae Nobuyuki Takahashi |
| author_sort | Satoshi Kumakura |
| collection | DOAJ |
| description | Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD<sup>+</sup> in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD<sup>+</sup>, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD<sup>+</sup> supply, which accelerated NAD<sup>+</sup>-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention. |
| first_indexed | 2024-03-09T05:15:41Z |
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| id | doaj.art-1822a016ac1248849183965b705d7e0c |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T05:15:41Z |
| publishDate | 2021-01-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-1822a016ac1248849183965b705d7e0c2023-12-03T12:44:57ZengMDPI AGToxins2072-66512021-01-011315010.3390/toxins13010050Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney DiseaseSatoshi Kumakura0Emiko Sato1Akiyo Sekimoto2Yamato Hashizume3Shu Yamakage4Mariko Miyazaki5Sadayoshi Ito6Hideo Harigae7Nobuyuki Takahashi8Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai 980-8578, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanNicotinamide adenine dinucleotide (NAD<sup>+</sup>) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD<sup>+</sup> in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD<sup>+</sup>, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD<sup>+</sup> supply, which accelerated NAD<sup>+</sup>-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention.https://www.mdpi.com/2072-6651/13/1/50nicotinamideCKDNAD<sup>+</sup>adenine-induced CKD modelglycolysisKrebs cycle |
| spellingShingle | Satoshi Kumakura Emiko Sato Akiyo Sekimoto Yamato Hashizume Shu Yamakage Mariko Miyazaki Sadayoshi Ito Hideo Harigae Nobuyuki Takahashi Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease Toxins nicotinamide CKD NAD<sup>+</sup> adenine-induced CKD model glycolysis Krebs cycle |
| title | Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease |
| title_full | Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease |
| title_fullStr | Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease |
| title_full_unstemmed | Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease |
| title_short | Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease |
| title_sort | nicotinamide attenuates the progression of renal failure in a mouse model of adenine induced chronic kidney disease |
| topic | nicotinamide CKD NAD<sup>+</sup> adenine-induced CKD model glycolysis Krebs cycle |
| url | https://www.mdpi.com/2072-6651/13/1/50 |
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