Effect of Cinacalcet on the Redox Status of Albumin in Secondary Hyperparathyroidism Patients Receiving Hemodialysis
Effect of Cinacalcet on the Redox Status of Albumin in Secondary Hyperparathyroidism Patients Receiving Hemodialysis
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DOI：
10.1248/bpb.b20-00472
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发表时间：
2020-10-01
影响因子：
2
通讯作者：
Maruyama, Toru
中科院分区：
文献类型：
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作者：
Imafuku, Tadashi;Tanaka, Motoko;Maruyama, Toru
慢性肾病（CKD）患者继发性甲状旁腺功能亢进（SHPT）的心血管疾病（CVD）的风险增加。西那卡塞是一种拟钙剂，可通过抑制SHPT患者的甲状旁腺激素（PTH）产生来恢复受损的内皮功能。然而，其作用的潜在机制仍然未知。本研究旨在检查西那卡塞对人血清白蛋白（HSA）氧化还原状态的影响，HSA是评估接受血液透析的SHPT患者内皮氧化损伤的可靠标志物。西那卡塞给予6名SHPT患者8周。治疗4周后，西那卡塞通过增加还原型HSA显著降低氧化白蛋白比率，氧化白蛋白比率是还原型和氧化型HSA的比率。西那卡塞还能增强SHPT患者血清中HSA的自由基清除能力，提示其可恢复受损的血管抗氧化能力。有趣的是，SHPT患者的氧化白蛋白比率显著高于血液透析患者。此外，全段PTH水平的变化与氧化白蛋白比值显著相关。因此，PTH可能会诱导SHPT患者的氧化应激。事实上，PTH的活性类似物增加了人内皮细胞中活性氧的产生。因此，西那卡塞通过其药理作用表现出抗氧化活性。此外，西那卡塞本身显示出自由基清除活性。总之，西那卡塞通过抑制PTH产生和部分通过其自由基清除作用改善HSA的氧化还原状态。
Chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT) have an increased risk of cardiovascular disease (CVD). Cinacalcet is a calcimimetic that permits impaired endothelial functions to be recovered via inhibiting parathyroid hormone (PTH) production in SHPT patients. However, the underlying mechanism for its action remains unknown. The purpose of this study was to examine the effect of cinacalcet on the redox state of human serum albumin (HSA), a reliable marker for assessing endothelial oxidative damage in SHPT patients who were receiving hemodialysis. Cinacalcet was administered to six SHPT patients for a period of 8 weeks. After 4 weeks of treatment, cinacalcet significantly decreased the oxidized albumin ratio which is a ratio of reduced and oxidized forms of HSA via increasing reduced form of HSA. Moreover, the radical scavenging abilities of HSA that was isolated from SHPT patients were increased by cinacalcet, suggesting the recovery of the impaired vascular anti-oxidant ability. Interestingly, the oxidized albumin ratio in SHPT patients was significantly higher than that in hemodialysis patients. In addition, the changes of intact PTH levels were significantly correlated with the oxidized albumin ratio. It therefore appears that PTH may induce oxidative stress in SHPT patients. In fact, an active analogue of PTH increased the production of reactive oxygen species in human endothelial cells. Thus, cinacalcet exhibits antioxidative activity through its pharmacological action. Additionally, cinacalcet itself showed radical scavenging activity. In conclusion, cinacalcet improves the redox status of HSA by inhibiting PTH production and partially by its radical scavenging action.