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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Elsevier
2022-02-01
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Series: | Journal of Functional Foods |
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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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format | Article |
id | doaj.art-88fbfaa6a10a496cb6f5216f75497dfa |
institution | Directory Open Access Journal |
issn | 1756-4646 |
language | English |
last_indexed | 2024-12-24T03:28:43Z |
publishDate | 2022-02-01 |
publisher | Elsevier |
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series | Journal of Functional Foods |
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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