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Dergiler / The European Research Journal / 2023 / Cilt: 9 - Sayı: 3

Can tolvaptan usage cause cytotoxicity? An in vitro study

Beril ERDEM TUNÇDEMİR
Sayfa
454–460
Yayın Tarihi
2023-05-04
DOI
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Since low concentrations of tolvaptan for a short time treatment is enough for its PC role, it may not show any cytotoxic effect on cells which is coherent with our results.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Objectives: Tolvaptan is a nonpeptide V2 (vasopressin) receptor antagonist which is commonly used for treatment of hypernatremia.
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Temel Bulgular & Veri:Besides it is mostly used for rescue strategies of mutant V2 receptors which are responsible for congenital type of Nephrogenic Diabetes insipidus (NDI) as a pharmacological chaperone (PC) treatment.
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Sonuç & Katkı:Since low concentrations of tolvaptan for a short time treatment is enough for its PC role, it may not show any cytotoxic effect on cells which is coherent with our results.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Tolvaptan · cytotoxicity · cell culture

Abstract

Objectives: Tolvaptan is a nonpeptide V2 (vasopressin) receptor antagonist which is commonly used for treatment of hypernatremia. Besides it is mostly used for rescue strategies of mutant V2 receptors which are responsible for congenital type of Nephrogenic Diabetes insipidus (NDI) as a pharmacological chaperone (PC) treatment. Tolvaptan is metabolized by CYP3A4 and usage of tolvaptan may cause cytotoxicity which can be prevented by antioxidants. The aim of this study is investigating cytotoxic effect of tolvaptan on COS-1 cells and preventing it via antioxidants such as Vitamin C and N-acetyl cysteine (NAC). Methods: To measure cytotoxicity of tolvaptan, COS-1 cells were separated in three groups; tolvaptan, tolvaptan+Vitamin C and tolvaptan+NAC. 24 h after cells were seeded in 96-well plates, they were treated with different concentrations of tolvaptan, tolvaptan+Vitamin C and tolvaptan+NAC. After 24 h incubation, the (3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide) [MTT] analysis were performed and GraphPad Prism 5.01 for Windows was used for statistical analysis. Results: According to results of MTT assay, treatment with tolvaptan did not decrease cell viability except that treatment of 10-5 M tolvaptan showed significantly decrase on cell viability compared to control group. At the concentration of 10-9 M, there was significantly different cell viability between treated with tolvaptan and tolvaptan+Vitamin C. Conclusions: Tolvaptan may show its cytotoxic effects when it is used for the treatment of hyponatremia than its usage of as a PC. Since low concentrations of tolvaptan for a short time treatment is enough for its PC role, it may not show any cytotoxic effect on cells which is coherent with our results.

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Bu Makaleye Atıf Yap

TUNÇDEMİR, B. E. (2023). Can tolvaptan usage cause cytotoxicity? An in vitro study. The European Research Journal, Cilt: 9 - Sayı: 3, 454–460. https://ajindex.com/articles/888749

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Kaynakça (16)

  1. Ali F, Guglin M, Vaitkevicius P, Ghali JK. Therapeutic potential of vasopressin receptor antagonists. Drugs 2007;67:847-58
  2. Torres VE. Vasopressin receptor antagonists, heart failure, and polycystic kidney disease. Annu Rev Med 2015;66:195-210
  3. Yi JH, Shin HJ, Kim HJ. V2 receptor antagonist; tolvaptan. Electrolyte Blood Press 2011;9:50-4
  4. Bichet DG. What is the role of vaptans in routine clinical nephrology? Clin J Am Soc Nephrol 2012;7:700-3
  5. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, et al. Tolvaptan a selective oral vasopressin v2 receptor antagonist for hyponatremia. N Engl J Med 2006;355:2099-112
  6. Bhardwaj A. Neurological impact of vasopressin dysregulation and hyponatremia. Ann Neurol 2006;59:229-36
  7. De Luca L, Klein L, Udelson JE, Orlandi C, Sardella G, Fedele F, et al. Hyponatremia in patients with heart failure. Am J Cardiol 2005;96:19L-23L
  8. Goldberg A, Hammerman H, Petcherski S, Nassar M, Zdorovyak A, Yalonetsky S, et al. Hyponatremia and long-term mortality in survivors of acute ST-elevation myocardial infarction. Arch Intern Med 2006;166:781-6
  9. Wu Y, Beland FA, Chen S, Liu F, Guo L, Fang JL. Mechanisms of tolvaptan-induced toxicity in HepG2 cells. Biochem Pharmacol 2015;95:324-36
  10. Zmily HD, Daifallah S, Ghali JK. Tolvaptan, hyponatremia, and heart failure. Int J Nephrol Renovasc Dis 2011;4:57-71
  11. Rangarajan B, Binoy V, Hingmire SS, Noronha V. Tolvaptan. South Asian J Cancer 2014;3:182-4
  12. Gheorghiade M, Konstam MA, Burnett JC, Grinfeld L, Maggioni A, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA 2007;297:1332-43
  13. Gheorghiade M, Orlandi C, Burnett JC, Demets D, Grinfeld L, Maggioni A, et al. Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST). J Card Fail 2005;11:260-9
  14. Konstam MA, Gheorghiade M, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 2007;297:1319-31
  15. Erdem Tuncdemir B, Mergen H, Saglar Ozer E. Evaluation of pharmacochaperone mediated rescue of mutant V2 receptor proteins. Eur J Pharmacol 2019;865:172803
  16. Tao YX, Conn PM. Pharmacoperones as novel therapeutics for