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Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways

High-fat diet (HFD)-induced obesity has been involved in the development of diabetic nephropathy (DN). Tenovin-1, a potent selective SIRT1/2 inhibitor, regulates various target proteins. The present study evaluated the protective effect of Tenovin-1 against renal fibrosis in HFD-induced Zucker diabe...

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Autores principales: Kundu, Amit, Gali, Sreevarsha, Sharma, Swati, Park, Jae Hyeon, Kyung, So Young, Kacew, Sam, Kim, In Su, Lee, Kwang Youl, Kim, Hyung Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495519/
https://www.ncbi.nlm.nih.gov/pubmed/36139886
http://dx.doi.org/10.3390/antiox11091812
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author Kundu, Amit
Gali, Sreevarsha
Sharma, Swati
Park, Jae Hyeon
Kyung, So Young
Kacew, Sam
Kim, In Su
Lee, Kwang Youl
Kim, Hyung Sik
author_facet Kundu, Amit
Gali, Sreevarsha
Sharma, Swati
Park, Jae Hyeon
Kyung, So Young
Kacew, Sam
Kim, In Su
Lee, Kwang Youl
Kim, Hyung Sik
author_sort Kundu, Amit
collection PubMed
description High-fat diet (HFD)-induced obesity has been involved in the development of diabetic nephropathy (DN). Tenovin-1, a potent selective SIRT1/2 inhibitor, regulates various target proteins. The present study evaluated the protective effect of Tenovin-1 against renal fibrosis in HFD-induced Zucker diabetic fatty (ZDF) rats. Rats were fed a normal chow diet or HFD. Tenovin-1 (45 mg/kg) administered to HFD-fed rats decreased inflammatory cytokine expression in the serum of the rats. The antioxidant status and oxidative damage to lipids or DNA were significantly restored by Tenovin-1. Additionally, Tenovin-1 reduced the levels of blood urea nitrogen (BUN), serum creatinine (sCr), microalbumin, and urinary protein-based biomarkers in the urine of HFD-fed rats. The abnormal architecture of the kidney and pancreas was restored by Tenovin-1 administration. Tenovin-1 also reduced apoptosis in the kidneys of the HFD-fed rats and HG-treated NRK-52E cells. It significantly lowered the levels of ECM proteins in the kidneys of HFD-fed rats and HG-treated NRK-52E cells. Additionally, Tenovin-1 markedly reduced claudin-1, SIRT1, and SIRT2, but increased SIRT3 and SIRT4 in HFD-fed rats and NRK-52E cells treated with HG. Furthermore, Tenovin-1 altered epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-β (PDGFR-β), and signal transducer and activator of transcription 3 (STAT3) levels in the kidneys of HFD-fed rats. Conclusively, this study shows that Tenovin-1 can be a potential candidate drug for the treatment of HFD-induced renal fibrosis, in vivo and in vitro models.
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spelling pubmed-94955192022-09-23 Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways Kundu, Amit Gali, Sreevarsha Sharma, Swati Park, Jae Hyeon Kyung, So Young Kacew, Sam Kim, In Su Lee, Kwang Youl Kim, Hyung Sik Antioxidants (Basel) Article High-fat diet (HFD)-induced obesity has been involved in the development of diabetic nephropathy (DN). Tenovin-1, a potent selective SIRT1/2 inhibitor, regulates various target proteins. The present study evaluated the protective effect of Tenovin-1 against renal fibrosis in HFD-induced Zucker diabetic fatty (ZDF) rats. Rats were fed a normal chow diet or HFD. Tenovin-1 (45 mg/kg) administered to HFD-fed rats decreased inflammatory cytokine expression in the serum of the rats. The antioxidant status and oxidative damage to lipids or DNA were significantly restored by Tenovin-1. Additionally, Tenovin-1 reduced the levels of blood urea nitrogen (BUN), serum creatinine (sCr), microalbumin, and urinary protein-based biomarkers in the urine of HFD-fed rats. The abnormal architecture of the kidney and pancreas was restored by Tenovin-1 administration. Tenovin-1 also reduced apoptosis in the kidneys of the HFD-fed rats and HG-treated NRK-52E cells. It significantly lowered the levels of ECM proteins in the kidneys of HFD-fed rats and HG-treated NRK-52E cells. Additionally, Tenovin-1 markedly reduced claudin-1, SIRT1, and SIRT2, but increased SIRT3 and SIRT4 in HFD-fed rats and NRK-52E cells treated with HG. Furthermore, Tenovin-1 altered epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-β (PDGFR-β), and signal transducer and activator of transcription 3 (STAT3) levels in the kidneys of HFD-fed rats. Conclusively, this study shows that Tenovin-1 can be a potential candidate drug for the treatment of HFD-induced renal fibrosis, in vivo and in vitro models. MDPI 2022-09-14 /pmc/articles/PMC9495519/ /pubmed/36139886 http://dx.doi.org/10.3390/antiox11091812 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kundu, Amit
Gali, Sreevarsha
Sharma, Swati
Park, Jae Hyeon
Kyung, So Young
Kacew, Sam
Kim, In Su
Lee, Kwang Youl
Kim, Hyung Sik
Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways
title Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways
title_full Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways
title_fullStr Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways
title_full_unstemmed Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways
title_short Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways
title_sort tenovin-1 ameliorates renal fibrosis in high-fat-diet-induced diabetic nephropathy via antioxidant and anti-inflammatory pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495519/
https://www.ncbi.nlm.nih.gov/pubmed/36139886
http://dx.doi.org/10.3390/antiox11091812
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