Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling

This study examined if sirtuin-1 (SIRT1) signaling mediates the nephroprotective effect of kaempferol in doxorubicin (DOX)-treated rats. Rats were divided into control, kaempferol, DOX, kaempferol + DOX, and kaempferol + DOX + EX-527 (a SIRT1 inhibitor). Kaempferol preserved the kidney structure and...

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Main Authors: Reham I. Alagal, Nora A. AlFaris, Ghedeir M. Alshammari, Jozaa Z. ALTamimi, Lujain A. AlMousa, Mohammed Abdo Yahya
Format: Article
Language:English
Published: Elsevier 2022-02-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464621005673
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author Reham I. Alagal
Nora A. AlFaris
Ghedeir M. Alshammari
Jozaa Z. ALTamimi
Lujain A. AlMousa
Mohammed Abdo Yahya
author_facet Reham I. Alagal
Nora A. AlFaris
Ghedeir M. Alshammari
Jozaa Z. ALTamimi
Lujain A. AlMousa
Mohammed Abdo Yahya
author_sort Reham I. Alagal
collection DOAJ
description This study examined if sirtuin-1 (SIRT1) signaling mediates the nephroprotective effect of kaempferol in doxorubicin (DOX)-treated rats. Rats were divided into control, kaempferol, DOX, kaempferol + DOX, and kaempferol + DOX + EX-527 (a SIRT1 inhibitor). Kaempferol preserved the kidney structure and function in DOX-treated rats by attenuating the impairment in urine volume, albumin/creatinine excretion, and creatinine clearance. It also reduced the renal expression of Bax and cleaved caspase-3 and the generation of the reactive oxygen species, malondialdehyde, tumor necrosis factor-α, and interleukin-6 but stimulated levels of glutathione and superoxide dismutase and mRNA of Bcl2. Kaempferol also increased renal mRNA, protein levels, and nuclear activities of SIRT1 that was associated with increased acetylation of both the nuclear factor erythroid 2–related factor 2 (Nrf2) and the nuclear factor-kappa beta (NF-κB). These effects were prevented by co-treatment with EX-527. In conclusion, kaempferol alleviated DOX-induced nephropathy, at least by upregulating and activating SIRT1.
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spelling doaj.art-88fbfaa6a10a496cb6f5216f75497dfa2022-12-21T17:17:17ZengElsevierJournal of Functional Foods1756-46462022-02-0189104918Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signalingReham I. Alagal0Nora A. AlFaris1Ghedeir M. Alshammari2Jozaa Z. ALTamimi3Lujain A. AlMousa4Mohammed Abdo Yahya5Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaNutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaDepartment of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaNutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaNutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; Corresponding author at: Riyadh 11671, P.O. Box 84428, Saudi Arabia.Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaThis study examined if sirtuin-1 (SIRT1) signaling mediates the nephroprotective effect of kaempferol in doxorubicin (DOX)-treated rats. Rats were divided into control, kaempferol, DOX, kaempferol + DOX, and kaempferol + DOX + EX-527 (a SIRT1 inhibitor). Kaempferol preserved the kidney structure and function in DOX-treated rats by attenuating the impairment in urine volume, albumin/creatinine excretion, and creatinine clearance. It also reduced the renal expression of Bax and cleaved caspase-3 and the generation of the reactive oxygen species, malondialdehyde, tumor necrosis factor-α, and interleukin-6 but stimulated levels of glutathione and superoxide dismutase and mRNA of Bcl2. Kaempferol also increased renal mRNA, protein levels, and nuclear activities of SIRT1 that was associated with increased acetylation of both the nuclear factor erythroid 2–related factor 2 (Nrf2) and the nuclear factor-kappa beta (NF-κB). These effects were prevented by co-treatment with EX-527. In conclusion, kaempferol alleviated DOX-induced nephropathy, at least by upregulating and activating SIRT1.http://www.sciencedirect.com/science/article/pii/S1756464621005673KaempferolDoxorubicinSIRT1Nrf2NF-κBOxidative stress
spellingShingle Reham I. Alagal
Nora A. AlFaris
Ghedeir M. Alshammari
Jozaa Z. ALTamimi
Lujain A. AlMousa
Mohammed Abdo Yahya
Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling
Journal of Functional Foods
Kaempferol
Doxorubicin
SIRT1
Nrf2
NF-κB
Oxidative stress
title Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling
title_full Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling
title_fullStr Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling
title_full_unstemmed Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling
title_short Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling
title_sort kaempferol attenuates doxorubicin mediated nephropathy in rats by activating sirt1 signaling
topic Kaempferol
Doxorubicin
SIRT1
Nrf2
NF-κB
Oxidative stress
url http://www.sciencedirect.com/science/article/pii/S1756464621005673
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AT ghedeirmalshammari kaempferolattenuatesdoxorubicinmediatednephropathyinratsbyactivatingsirt1signaling
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