Lacidipine Attenuates Apoptosis via a Caspase-3 Dependent Pathway in Human Kidney Cells

Abstract

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

Glycyrrhizin protects mice against renal ischemia-reperfusion injury through inhibition of apoptosis and inflammation by downregulating p38 mitogen-activated protein kinase signaling

“…Among the apoptotic mediators, activated caspase-3 acts as a final executor, as it regulates the extrinsic and intrinsic pathways of apoptosis (18,19). Furthermore, caspase-3-mediated cell apoptosis has been demonstrated to be essential in I/R-induced organ damage (20); thus, the effect of glycyrrhizin on I/R-induced renal cell apoptosis was investigated in the present study.…”

Computationally Assisted (Solid-State Density Functional Theory) Structural (X-ray) and Vibrational Spectroscopy (FT-IR, FT-RS, TDs-THz) Characterization of the Cardiovascular Drug Lacidipine

“…4 In addition, it was suggested that LCDP can protect the patients' kidney cells from apoptosis induced by adenosine triphosphate (ATP) depletion and their recovery by regulating the caspase-3 pathway. 5 Furthermore, LCDP was found to protect stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation, evoked by a salt-rich diet, which may contribute to its beneficial effect against end-organ damage and stroke. 6 Finally, recent studies have confirmed its significance as an antibacterial and antitoxic compound.…”

“…Therefore, LCDP is an attractive therapy agent for the long-term management of essential hypertension. , As with other members of its class, it has shown potentially beneficial anti-atherosclerotic properties by affecting cellular cholesterol metabolism . In addition, it was suggested that LCDP can protect the patients’ kidney cells from apoptosis induced by adenosine triphosphate (ATP) depletion and their recovery by regulating the caspase-3 pathway . Furthermore, LCDP was found to protect stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation, evoked by a salt-rich diet, which may contribute to its beneficial effect against end-organ damage and stroke .…”

Protective Effect of Peptide Calcium Channel Blocker Omega-Hexatoxin-Hv1a on Epithelial Cell during Ischemia–Reperfusion Injury

“…Studies show that benidipine reduces apoptosis and necrosis when modeling conditions of ischemia–reperfusion in experiments in vivo [ 31 , 32 ]. A similar effect is manifested by the action of lacidipine, a blocker of slow calcium channels from the group of dihydropyridine derivatives, when ATP is depleted in the epithelial cells of the renal tubules [ 33 ], and also when adding verapamil to ischemic intestinal epithelial cells. In the latter case, the activation of the mechanisms of cell death is associated with a change in the distribution of integrins and depolymerization of F-actin [ 34 ].…”