{"title":"Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis","authors":"","doi":"10.1016/j.freeradbiomed.2024.09.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism.</p></div><div><h3>Methods</h3><p>1. Patients with CKD stage 2–5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected.</p></div><div><h3>Results</h3><p>1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride.</p></div><div><h3>Conclusion</h3><p>Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.</p></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Free Radical Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891584924006543","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism.
Methods
1. Patients with CKD stage 2–5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected.
Results
1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride.
Conclusion
Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.
期刊介绍:
Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.