Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences

Jakutiene, Eitautė; Grikinienė, Jurgita; Vaitkevičius, Arūnas; Tschaika, Marina; Didžiapetrienė, Janina; Stakišaitis, Donatas

doi:10.1186/1471-2210-7-9

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…The new VPA effect was observed: The VPA diuretic effect and its relation to Na + , K + , Cl − and Mg 2+ 24-hour urinary excretion; the total 24-hour diuresis and the 24-hour diuresis per 100 g of body weight were found to be significantly higher in VPA-treated rats of both genders than in the control groups with gender-related differences. 21 –23 These data support the possible NKCC2 inhibition by VPA, as the increased diuresis and increased saluretic effect accompanied by an increase in divalent ions in the urine is characteristic of the NKCC2 inhibition in kidneys. 24,37 A gender difference in the NKCC2 in rat kidneys is known: The lower abundance of NKCC2 was observed in females compared with males.…”

Section: Discussionsupporting

confidence: 65%

“…The experimental data indicate that VPA has aquaretic and saluretic effects in rats: Alongside its diuretic effect, VPA enhances Na þ , Cl À , and K þ excretion with 24-hour urine. 21,22 Also, VPA significantly increases the urinary excretion of magnesium ions. 23 The abovedescribed saluretic effects of VPA on urinary ion excretion could be characteristic for the Na-K-2Cl (NKCC2) inhibition in rat kidney because NKCC2 inhibitors increase urinary monovalent as well as divalent cation excretion.…”

Section: Introductionmentioning

confidence: 96%

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Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

et al. 2019

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Objective: The NKCC1 is a recognized tumorigenesis marker as it is important for tumor cell proliferation, differentiation, apoptosis, and tumor progression. The study aim was to investigate the effect of sodium valproate (VPA) on thymus NKCC1 RNA expression. Material and Methods: Wistar rats, age 4 to 5 weeks, were investigated in the control and VPA-treated male and female gonad-intact and castrated groups. The treatment duration with VPA 300 mg/kg/d was 4 weeks. Rat thymus was weighted; its lobe was taken for the expression of NKCC1 RNA determined by the real-time polymerase chain reaction method. Results: The RNA expression of the Slc12a2 gene was found to be significantly higher in the gonad-intact male control compared with the gonad-intact female control ( P = .04). There was a gender-related VPA treatment effect on NKCC1 RNA expression in thymus: The Slc12a2 gene RNA expression level was found to be decreased in VPA-treated gonad-intact males ( P = .015), and no significant VPA effects were found in the castrated males and in the gonad-intact and castrated females compared with the respective controls ( P > .05). Conclusions: The study showed a gender-related difference in the NKCC1 RNA expression in rat thymus. The VPA decreases the NKCC1 expression in the thymus only in gonad-intact male rats. The NKCC1 RNA expression downregulation by VPA could be important for further VPA pharmacological studies in oncology.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 96%

Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

et al. 2019

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“…The loss of efficacy may be explained by pharmacokinetic tolerance, since VPA plasma levels declined during treatment. This is likely to be due to the fact that the rats gradually excrete more VPA via the urine during treatment, a phenomenon that has been described before (Jakutiene et al., 2007). However, mean VPA plasma levels in the rat were 124 μg/ml at day 3 and 67 μg/ml at day 7, which is still within or above the tentative target range (Patsalos et al., 2008).…”

Section: Discussionmentioning

confidence: 70%

Improved seizure control by alternating therapy of levetiracetam and valproate in epileptic rats

Vliet¹,

Edelbroek²,

Gorter³

2010

Epilepsia

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SUMMARYPurpose: Tolerance to drug treatment is a serious problem in the treatment of epilepsy. We previously showed that tolerance to levetiracetam (LEV) developed within 4 days after the start of the treatment in a rat model for spontaneous seizures after electrically induced status epilepticus.In the current study we tested whether the development of tolerance to LEV could be prevented by alternating between LEV and valproate (VPA) treatment. Methods: Before starting the alternating therapy with LEV and VPA (3 day LEV-3 day VPA, two cycles), we assessed the efficacy of VPA monotherapy by administering VPA to chronic epileptic rats via osmotic minipumps during 7 days. The anticonvulsive effects were determined by continuous video-EEG (electroencephalography) monitoring, and the concentration of VPA and LEV was measured in plasma using gas chromatography.Results: VPA significantly suppressed spontaneous seizures in chronic epileptic rats for 5 days. Hereafter, seizure frequency increased to pretreatment values despite adequate VPA blood levels. Seizure duration was reduced for 6 days during treatment. Seizure severity was reduced throughout the 7-day treatment period. Alternating treatment of LEV and VPA did not prevent development of tolerance; however, seizures were suppressed significantly longer compared to VPA and LEV monotherapy. Conclusions: Because alternating treatment with LEV and VPA led to a prolonged effective seizure control in the animal model, it would be worthwhile to explore the possibilities of using an alternating treatment protocol in pharmacoresistant patients in whom an effective treatment is hampered by tolerance to antiepileptic drugs.

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“…Reduction of thymus weight was induced after prenatal exposure to VPA in male but not in female rat offsprings (Schneider et al, 2008). VPA was shown to enhance the urinary excretion of sodium and chloride ions in Wistar rats of both genders, but the 24-h chloriduretic response was found to be gender-related (Grikiniene et al, 2005;Jakutiene et al, 2007): in male rats the rate of excretion was higher than in female. The intracellular chloride concentration would be one of the critical messengers in cell growth/proliferation and differentiation processes (Hiraoka et al, 2010;Ohsawa et al, 2010;Shiozaki et al, 2006).…”

Section: Discussionmentioning

confidence: 90%

Sodium valproate effect on the structure of rat glandule thymus: Gender-related differences

Valančiūtė

Mozūraitė

Balnytė

et al. 2015

Experimental and Toxicologic Pathology

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Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences

Cited by 10 publications

References 34 publications

Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

Improved seizure control by alternating therapy of levetiracetam and valproate in epileptic rats

Sodium valproate effect on the structure of rat glandule thymus: Gender-related differences

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