Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis

• Published in: Free radical biology & medicine 2024-11, Vol.224, p.554-563
• Main Authors: Zhu, Li, Wang, Lu-yu, Zhang, Ting, Wang, Qi-wen, Zhang, Chun-sheng, Zhou, Zhi-hua, Qian, Jia-long, Liang, Yan, Zhou, Chuan, Bu, Ren, Su, Chang-hai, Dong, Li-sen, Wang, Yong, Du, Xiao-li, Cao, Xiao-dong, Gao, Jie, Liu, Yang, Li, Bing, Li, Gang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Caspase 3 - genetics; Caspase 3 - metabolism; Cell Line; Disease Models, Animal; Durapatite; Humans; Intravenous injection; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Lanthanum - pharmacology; Lanthanum chloride; Male; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mitophagy; Mitophagy - drug effects; nHAp; Oxidative Stress - drug effects; Rats; Rats, Wistar; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2024.09.007

To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. 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. 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. 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. [Display omitted] •Lanthanum chloride has a protective effect against kidney injury in CKD.•Nano-hydroxyapatite was found in both in vitro and in vivo CKD models, and it plays a major role in alleviating CKD.•Lanthanum chloride may change nano-hydroxyapatite morphology, inhibiting mitophagy and apoptosis, improving CKD renal injury.