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Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.
- Source :
-
BMC pharmacology & toxicology [BMC Pharmacol Toxicol] 2023 Dec 21; Vol. 24 (1), pp. 82. Date of Electronic Publication: 2023 Dec 21. - Publication Year :
- 2023
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Abstract
- Background: Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.<br />Materials and Methods: Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.<br />Results: Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.<br />Conclusion: These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.<br /> (© 2023. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2050-6511
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC pharmacology & toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 38129888
- Full Text :
- https://doi.org/10.1186/s40360-023-00722-6