High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats
We investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/3038 |
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| author | Agata Wrońska Jacek Kieżun Zbigniew Kmieć |
| author_facet | Agata Wrońska Jacek Kieżun Zbigniew Kmieć |
| author_sort | Agata Wrońska |
| collection | DOAJ |
| description | We investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced the thickening of basement membranes, but 0.5% fenofibrate exacerbated interstitial fibrosis. The PCR array for stress and toxicity-related targets showed that 0.1% fenofibrate mildly downregulated, whereas 0.5% upregulated multiple genes. In young rats, 0.1% fenofibrate increased some antioxidant genes’ expression and decreased the immunoreactivity of oxidative stress marker 4-HNE. However, the activation of cellular antioxidant defenses was impaired in old rats. Fenofibrate modulated the expression of factors involved in hypoxia and osmotic stress signaling similarly in both age groups. Inflammatory response genes were variably modulated in the young rats, whereas old animals presented elevated expression of proinflammatory genes and TNFα immunoreactivity after 0.5% fenofibrate. In old rats, 0.1% fenofibrate more prominently than in young animals induced phospho-AMPK and PGC1α levels, and upregulated fatty acid oxidation genes. Our results show divergent effects of fenofibrate in young and old rat kidneys. The activation of multiple stress-associated effectors by high-dose fenofibrate in the aged kidney warrants caution when applying fenofibrate therapy to the elderly. |
| first_indexed | 2024-04-25T00:27:19Z |
| format | Article |
| id | doaj.art-07b42b4cd2e343b9942feb2b05947cd9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:27:19Z |
| publishDate | 2024-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-07b42b4cd2e343b9942feb2b05947cd92024-03-12T16:47:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01255303810.3390/ijms25053038High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old RatsAgata Wrońska0Jacek Kieżun1Zbigniew Kmieć2Department of Histology, Faculty of Medicine, Medical University of Gdańsk, 80-210 Gdańsk, PolandDepartment of Human Histology and Embryology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, PolandDepartment of Histology, Faculty of Medicine, Medical University of Gdańsk, 80-210 Gdańsk, PolandWe investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced the thickening of basement membranes, but 0.5% fenofibrate exacerbated interstitial fibrosis. The PCR array for stress and toxicity-related targets showed that 0.1% fenofibrate mildly downregulated, whereas 0.5% upregulated multiple genes. In young rats, 0.1% fenofibrate increased some antioxidant genes’ expression and decreased the immunoreactivity of oxidative stress marker 4-HNE. However, the activation of cellular antioxidant defenses was impaired in old rats. Fenofibrate modulated the expression of factors involved in hypoxia and osmotic stress signaling similarly in both age groups. Inflammatory response genes were variably modulated in the young rats, whereas old animals presented elevated expression of proinflammatory genes and TNFα immunoreactivity after 0.5% fenofibrate. In old rats, 0.1% fenofibrate more prominently than in young animals induced phospho-AMPK and PGC1α levels, and upregulated fatty acid oxidation genes. Our results show divergent effects of fenofibrate in young and old rat kidneys. The activation of multiple stress-associated effectors by high-dose fenofibrate in the aged kidney warrants caution when applying fenofibrate therapy to the elderly.https://www.mdpi.com/1422-0067/25/5/3038agingkidneyfenofibratecellular stress |
| spellingShingle | Agata Wrońska Jacek Kieżun Zbigniew Kmieć High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats International Journal of Molecular Sciences aging kidney fenofibrate cellular stress |
| title | High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats |
| title_full | High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats |
| title_fullStr | High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats |
| title_full_unstemmed | High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats |
| title_short | High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats |
| title_sort | high dose fenofibrate stimulates multiple cellular stress pathways in the kidney of old rats |
| topic | aging kidney fenofibrate cellular stress |
| url | https://www.mdpi.com/1422-0067/25/5/3038 |
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