Related Experiment Video
Updated: Jul 7, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway
Hadi Shirzad1, Seyed Amin Mousavinezhad1, Mohammad Panji1
1Research Center for Life, Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarters, Tehran, Iran.
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.
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.
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.
Conclusion:
These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.
