CoChat
Sign Up
Cited by 27Chronic Kidney Disease and DiabetesSirtuins and Resveratrol in MedicineRenal Diseases and Glomerulopathies

Protective effect of EX-527 against high-fat diet-induced diabetic nephropathy in Zucker rats

Kundu, Amit, Richa, Sachan, Dey, Prasanta, Kim, Kyeong Seok, Son, Ji Yeon, Kim, Hae Ri, Lee, Seok-Yong, Lee, Byung-Hoon +4 more·2020·Toxicology and Applied Pharmacology
DOI 10.1016/j.taap.2020.114899
Open this paper in CoChat — free account

Abstract

High-fat diet (HFD)-induced obesity is implicated in diabetic nephropathy (DN). EX-527, a selective Sirtuin 1 (SIRT1) inhibitor, has multiple biological functions; however, its protective effect against DN is yet to be properly understood. This study was aimed to explore the protective effect of EX-527 against DN in HFD-induced diabetic Zucker (ZDF) rats. After 21 weeks of continually feeding HFD to the rats, the apparent characteristics of progressive DN were observed, which included an increase in kidney weight (~160%), hyperglycemia, oxidative stress, and inflammatory cytokines, and subsequent renal cell damage. However, the administration of EX-527 for 10 weeks significantly reduced the blood glucose concentration and kidney weight (~59%). Furthermore, EX-527 significantly reduced the serum concentration of transforming growth factor-β1 (49%), interleukin (IL)-1β (52%), and IL-6 in the HFD-fed rats. Overall, the antioxidant activities significantly increased, and oxidative damage to lipids or DNA was suppressed. Particularly, EX-527 significantly reduced blood urea nitrogen (81%), serum creatinine (71%), microalbumin (43%), and urinary excretion of protein-based biomarkers. Histopathological examination revealed expansion of the extracellular mesangial matrix and suppression of glomerulosclerosis following EX-527 administration. EX-527 downregulated the expression of α-SMA (~64%), TGF-β (25%), vimentin, α-tubulin, fibronectin, and collagen-1 in the kidneys of the HFD-fed rats. Additionally, EX-527 substantially reduced claudin-1 and SIRT1 expression, but increased the expression of SIRT3 in the kidneys of the HFD-fed rats. EX-527 also inhibited the growth factor receptors, including EGFR, PDGFR-β, and STAT3, which are responsible for the anti-fibrotic effect of SIRT-1. Therefore, the administration of EX-527 protects against HFD-induced DN.

Integrity signals

Registry

Crossref · 10.1016/j.taap.2020.114899

Cites

105 of 105 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Ex-527 protects the organism against kidney damage caused by diabetes (diabetic nephropathy) by reduction of glucose levels and an increase in SIRT1 activities accompanied by simultaneous increase in SIRT3 activity in the kidneys.

    “Ex-527 has also been reported to protect the organism against kidney damage caused by diabetes (diabetic nephropathy). This effect is achieved by the reduction of glucose levels and an increase in SIRT1 activities accompanied by the simultaneous increase in SIRT3 activity in the kidneys (Kundu et al. 2020).”

    From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Kundu et al. 2020

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kundu, A., Richa, S., Dey, P., Kim, K. S., Son, J. Y., Kim, H. R., Lee, S.-Y., Lee, B.-H., Lee, K. Y., Kacew, S., Lee, B. M., & Kim, H. S.
Affiliations
  • Sungkyunkwan University (KR)
  • Seoul National University (KR)
  • Chonnam National University (KR)
  • University of Ottawa (CA)
Corresponding author
Kim, Hyung Sik
ORCID
Venue
Toxicology and Applied Pharmacology
Publisher
Elsevier BV
Published
2020-03
Volume
390
Pages
114899
ISSN
0041-008X (ISSN-L)
DOI
10.1016/j.taap.2020.114899
OpenAlex
W3003027056
Cited by
27
References
105
Citations by year
2025: 4 · 2024: 6 · 2023: 2 · 2022: 10 · 2021: 2 · 2020: 3
FWCI
2.67
Type
journal article
Language
en
Update notices
erratum (2020-09-01)
Open access
closed
Licence
Locations
  • Toxicology and Applied Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Research Foundation of Korea (NRF-2016R1A2B2011071, NRF-2017R1D1A1B03036571)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Keywords
EX527, SIRT1 inhibitors, diabetic nephropathy, high-fat diet, obesity, Zucker diabetic fatty rats, renal fibrosis, glomerulosclerosis, oxidative stress, inflammatory cytokines, TGF-β1, SIRT3, claudin-1, EGFR, PDGFRβ, STAT3
MeSH terms
Animals, Blood Glucose, Carbazoles, Diabetic Nephropathies, Gene Expression Regulation, Kidney, Male, Organ Size, Pancreas, Rats, Zucker, Biomarkers, Cytokines, Glycation End Products, Advanced, Oxidative Stress, Rats, Diet, High-Fat

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review