Effect of Cinacalcet on the Redox Status of Albumin in Secondary Hyperparathyroidism Patients Receiving Hemodialysis

  • Imafuku Tadashi
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Tanaka Motoko
    Department of Nephrology, Akebono Clinic
  • Tokunaga Koki
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Miyamura Shigeyuki
    Faculty of Pharmaceutical Sciences, Sojo University
  • Kato Hiromasa
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Tanaka Shoma
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Nakano Takehiro
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Hirata Kenshiro
    Faculty of Pharmaceutical Sciences, Sojo University
  • Kadowaki Daisuke
    Faculty of Pharmaceutical Sciences, Sojo University
  • Maeda Hitoshi
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Matsushita Kazutaka
    Department of Nephrology, Akebono Clinic
  • Otagiri Masaki
    Faculty of Pharmaceutical Sciences, Sojo University
  • Komaba Hirotaka
    Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine
  • Fukagawa Masafumi
    Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine
  • Watanabe Hiroshi
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Maruyama Toru
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

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<p>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 anti-oxidative 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.</p>

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