Characterization of tolvaptan response and its impact on the outcome for patients with heart failure

Hitomi, Yasuhiro; Nagatomo, Yuji; Yukino, Midori; Yumita, Yusuke; Kagami, Kazuki; Yasuda, Risako; Toya, Takumi; Namba, Takayuki; Masaki, Nobuyuki; Yada, Hirotaka; Adachi, Takeshi

doi:10.1016/j.jjcc.2021.04.014

Cited by 3 publications

(3 citation statements)

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“…COS cell line was used in this study because we have been functionally analyzed and showed res-cue potential of mutant V2 receptors via PCs in our previous and ongoing studies and therefore it was aimed to show cytotoxic effects of tolvaptan on COS-1 cells. In addition to PC studies, many of the other studies showed that tolvaptan is successful to increase serum sodium levels in patients with hyponatremia related with heart failure, cirrhosis and SIADH [27,28]. On the contrary, in the present time, tolvaptan are not recommended for routine use in patients with PKD.…”

Section: Early Onlinementioning

confidence: 85%

“…MTT is a reagent that is commonly used to define cell viability in cell culture studies. Formation of MTT formazan crystals is used to determine viable cells in this colorimetric method [28]. To measure the viability of the cells, after the incubation with tolvaptan and antioxidants of the cells, medium was removed and freshly prepared 100 μl 0.5 mg/ml MTT was added to the well and plates were incubated for 4 hours in 37°C in dark.…”

Section: Mtt Assaymentioning

confidence: 99%

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Can tolvaptan usage cause cytotoxicity? An in vitro study

Tuncdemir

2023

The European Research Journal

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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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Section: Early Onlinementioning

confidence: 85%

Section: Mtt Assaymentioning

confidence: 99%

Can tolvaptan usage cause cytotoxicity? An in vitro study

Tuncdemir

2023

The European Research Journal

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“…A recent study showed that the delayed start of tolvaptan administration was an independent predictor of diuretic resistance. 3) The treatment delay due to under dosing of tolvaptan may further enhance diuretic resistance. We found higher in-hospital mortality and longer hospital stays in patients in the dose escalation group compared to those without dose escalation.…”

mentioning

confidence: 99%