For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
26
views
33
references
 Top references
cited by
11
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      257
      similar
       All similar

      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before December 31, 2024

      About Blood Purification: 2.2 Impact Factor I 5.8 CiteScore I 0.782 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Nicotinamide Supplementation Attenuates Renal Interstitial Fibrosis via Boosting the Activity of Sirtuins

      research-article

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Progressive tubulointerstitial fibrosis (TIF) is the final common pathway leading to ESRD. There is an urgent need to develop effective approaches slowing the progression of TIF. Previous studies showed that systemic supplementation of nicotinamide (NAM) increases renal NAD<sup>+</sup> and reverses ischemic-reperfusion induced acute renal injury. However, the role and mechanism of NAM in TIF has been unclear. Methods: In vivo, we injected NAM (0.25 mg/g) 3 days before unilateral ureter obstruction (UUO) till day 7 post-operation. In vitro, mouse primary proximal tubular epithelial cells (PTCs), rat renal NRK-49F cells, and human renal proximal tubular epithelial cell (HK-2) were pretreated with the indicated concentration of NAM 1 h before incubation with transform growth factor-β1 (TGF-β1) or aristolochic acid (AA) for 24 or 48 h. To evaluate the role of sirtuins (SIRTs), PTCs were pretreated with EX527 or resveratrol 30 min before incubation with NAM and TGF-β1. Results: In the present study, we demonstrated that NAM supplementation prevented UUO-induced TIF, and AA-induced renal injury. NAM also decreased the expression of pro-fibrotic proteins and pro-inflammatory cytokines (IL-6 and TNF-α) and attenuated interstitial inflammation. In vitro experiment showed that, NAM inhibited AA-induced G2/M arrest of HK-2 cells by downregulating the expression of cyclin G1, a target gene of p53. In addition, NAM inhibited TGF-β1-induced fibroblast proliferation and activation shown as downregulated expression of collagen I, fibronectin, PCNA, cyclin D1, IL-6, and TNF-α. NAM decreased the acetylation of Smad3 and p53. EX527, an inhibitor of SIRT1, reversed the effect of NAM on TGF-β1-induced matrix protein production. However, resveratrol, a SIRT1 activator, did not further boost the protective effect of NAM on reducing matrix protein production. Conclusions: Taken together, these data indicate that NAM supplementation could inhibit TIF at least partially by boosting the activity of sirtuins.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          NAD+ and sirtuins in aging and disease.

          Shin-ichiro Imai, Leonard Guarente (2014)
          Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide. Copyright © 2014 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 312 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            PGC1α-dependent NAD biosynthesis links oxidative metabolism to renal protection

            Mei T. Tran, Zsuzsanna K. Zsengeller, Anders Berg … (2016)
            The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischemia. Indeed, acute kidney injury (AKI) affects 3% of all hospitalized patients. 1,2 Here we show that the mitochondrial biogenesis regulator, PGC1α, 3,4 is a pivotal determinant of renal recovery from injury by regulating NAD biosynthesis. Following renal ischemia, PGC1α−/− mice developed local deficiency of the NAD precursor niacinamide (Nam), marked fat accumulation, and failure to re-establish normal function. Remarkably, exogenous Nam improved local NAD levels, fat accumulation, and renal function in post-ischemic PGC1α−/− mice. Inducible tubular transgenic mice (iNephPGC1α) recapitulated the effects of Nam supplementation, including more local NAD and less fat accumulation with better renal function after ischemia. PGC1α coordinately upregulated the enzymes that synthesize NAD de novo from amino acids whereas PGC1α deficiency or AKI attenuated the de novo pathway. Nam enhanced NAD via the enzyme NAMPT and augmented production of the fat breakdown product beta-hydroxybutyrate (β-OHB), leading to increased prostaglandin PGE2, a secreted autocoid that maintains renal function. 5 Nam treatment reversed established ischemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of β-OHB signaling or prostaglandins similarly abolished PGC1α-dependent renoprotection. Given the importance of mitochondrial health in aging and the function of metabolically active organs, the results implicate Nam and NAD as key effectors for achieving PGC1α-dependent stress resistance.
            Article 0 comments Cited 215 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Safety of high-dose nicotinamide: a review.

              Jonathan Gale, P Bingley, R. Moore … (2000)
              Nicotinamide, the amide derivative of nicotinic acid, has over the past forty years been given at high doses for a variety of therapeutic applications. It is currently in trial as a potential means of preventing the onset of Type I (insulin-dependent) diabetes mellitus in high-risk, first-degree relatives. Nicotinamide is for regulatory purposes classed as a food additive rather than a drug and has not therefore required the formal safety evaluation normally expected of a new therapy. Because the safety of treatment with megadoses of vitamins cannot be assumed, a full literature review has been undertaken. The therapeutic index of nicotinamide is wide but at very high doses reversible hepatotoxicity has been reported in animals and humans. Minor abnormalities of liver enzymes can infrequently occur at the doses used for diabetes prevention. There is no evidence of teratogenicity from animal studies and nicotinamide is not in itself oncogenic; at very high doses it does however potentiate islet tumour formation in rats treated with streptozotocin or alloxan. There is no evidence of oncogenicity in man. Growth inhibition can occur in rats but growth in children is unaffected. Studies of its effects on glucose kinetics and insulin sensitivity are inconsistent but minor degrees of insulin resistance have been reported. The drug is well tolerated, especially in recent studies which have used relatively pure preparations of the vitamin. Experience to date therefore suggests that the ratio of risk to benefit of long-term nicotinamide treatment would be highly favourable, should the drug prove efficacious in diabetes prevention. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 gm/day and unsupervised use should be discouraged.
              Article 0 comments Cited 62 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (publisher-id): KDD
                Journal ID (pmc): KDD
                Journal ID (doi): 10.1159/issn.2296-9357
                Title: Kidney Diseases
                Publisher: S. Karger AG
                ISSN (Print): 2296-9381
                ISSN (Electronic): 2296-9357
                Publication date Subscription-year: 2021
                Publication date (Print): May 2021
                Publication date (Electronic): 11 January 2021
                Volume: 7
                Issue: 3
                Pages: 186-199
                Affiliations
                State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of Education), Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
                Author notes
                *Jing Nie, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Key Laboratory of Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, North Guangshou Avenue 1838, Guangzhou 510515 (China), niejing@smu.edu.cn
                Article
                Publisher ID: 510943 Other ID: Kidney Dis 2021;7:186–199
                DOI: 10.1159/000510943
                PubMed ID: 34179114
                SO-VID: 30f3a952-fe48-4f09-ab87-13c4ded04b30
                Copyright © © 2021 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 28 November 2019
                Date accepted : 18 August 2020
                Page count
                Figures: 8, Pages: 14
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Nicotinamide,Renal interstitial fibrosis,Sirtuins,G2/M arrest,Inflammation
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Nicotinamide, Renal interstitial fibrosis, Sirtuins, G2/M arrest, Inflammation

                Comments

                Comment on this article

                scite_

                Similar content257

                See all similar

                Cited by11

                See all cited by

                Most referenced authors210

                See all reference authors