Lacidipine attenuates apoptosis via a caspase-3 dependent pathway in human kidney cells

Acute kidney injury (AKI) is common in hospitalised patients and has a poor prognosis. Therefore, new therapeutic strategies are anticipated. Lacidipine, a novel third-generation dihydropyridine calcium channel blocker, has been demonstrated effective for hypertension. However, its potential effect on renal injury remains unknown. In the present study, an in vitro model of renal ischemia reperfusion (I/R) injury was used to investigate the protective effect and underlying mechanisms of lacidipine on human kidney cell (HKC) apoptosis.

HKCs were subjected to adenosine triphosphate (ATP) depletion and recovery (0.01 µM AA, depletion for 2 h and recovery for 30 min), with or without lacidipine (1 µM and 10 µM, 24 h), then cell viability and apoptosis were determined using the cell counting kit-8 (CCK-8) assay and Annexin V flow cytometry. The expression of Bcl-2, Bax, and cytochrome c (cyt c) was examined by western blot.

Antimycin A (AA) was found to induce apoptosis of HKCs. The proportion of early apoptosis and activity of caspase-3 peaked at 30 min after ATP depletion and recovery and were attenuated by lacidipine. The expression of cyt c and Bax was decreased, while that of Bcl-2 was increased significantly in lacidipine treated group.

We conclude that lacidipine protects HKCs against apoptosis induced by ATP depletion and recovery by regulating the caspase-3 pathway.