Sodium valproate effect on chloride metabolism in rats: A new approach to its possible anticancer mechanism

Donatas Stakišaitis, Jurgita Grikinienė, Vaidas Meilius, Janina Didziapetriene, Paulius Matusevicius

    Research output: Contribution to journalArticle

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    Abstract

    Aim: Sodium valproate (NaVP) defines a novel class of histone deacetylases (HDAC) inhibitors inducing differentiation of transformed cells by their antitumor properties. Earlier we have showed that single doses of NaVP havse natriuretic, kaliuretic and chloriduretic effects in rats. The chloriduretic effect of repeated NaVP doses has not previously been investigated. The aim of the present study was to define the peculiarities of 24 h urinary chloride (Cl–) excretion in young adult Wistar rats and to evaluate the related effects of single and repeated NaVP doses in a 10-day treatment. Materials and methods: 24 h urinary Cl–, creatinine and pH levels were measured in 14 control intact Wistar male rats and 13 Wistar male rats after a single per os administration of 300 mg/kg NaVP (VP rats), 5 Wistar male rats after 10 days of the daily intragastric administration of 300 mg/kg NaVP (VP-10 rats) and 5 matched control male rats. 24 h urine was collected keeping a rat alone in a special diuresis cage (Tecniplast, Italy) for 24 h with free access to tap water, without food, in the same temperature and light conditions. 24 h urinary Cl–, Na+ levels were analyzed with an EML- 105 electrolyte analyzer (Radiometer, Denmark). Urinary pH levels were measured with a pH/mV/ion meter (ION Meter pH 340/ION, Germany). Results: After a single dose and after 10 days of NaVP administration, 24 h total diuresis and 24 h diuresis per 100 g of body weight were significantly higher in VP and VP- 10 rats as compared with the respective control. 24 h urine Cl– excretion was significantly higher in VP and VP-10 rats than in matched controls.
    The study data shows that repeated NaVP doses enhance Cl– excretion with urine. Authors discuss the possible new mechanism of NaVP anticancer effects related to intracellular Cl– level changes. Conclusion: The understanding of the hypothesized NaVP mechanism may lead to the recognition of Cl– as an important mediator in tumor development and as a novel therapeutic target for cancer.
    Original languageEnglish
    Pages (from-to)256-261
    JournalTrace Elements and Electrolytes
    Volume29
    Issue number4 (4th Quarter)
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    Valproic Acid
    Metabolism
    Rats
    Chlorides
    Wistar Rats
    Diuresis
    Urine
    Histone Deacetylases
    pH meters
    Denmark
    Rat control
    Italy
    Electrolytes
    Germany
    Cell Differentiation
    Young Adult
    Creatinine
    Neoplasms
    Radiometers
    Body Weight

    Keywords

    • Sodium valproate
    • Chloride
    • Cancer

    Cite this

    Sodium valproate effect on chloride metabolism in rats : A new approach to its possible anticancer mechanism. / Stakišaitis, Donatas ; Grikinienė, Jurgita; Meilius, Vaidas; Didziapetriene, Janina; Matusevicius, Paulius.

    In: Trace Elements and Electrolytes, Vol. 29, No. 4 (4th Quarter), 2012, p. 256-261.

    Research output: Contribution to journalArticle

    Stakišaitis, Donatas ; Grikinienė, Jurgita ; Meilius, Vaidas ; Didziapetriene, Janina ; Matusevicius, Paulius. / Sodium valproate effect on chloride metabolism in rats : A new approach to its possible anticancer mechanism. In: Trace Elements and Electrolytes. 2012 ; Vol. 29, No. 4 (4th Quarter). pp. 256-261.
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    AU - Stakišaitis, Donatas

    AU - Grikinienė, Jurgita

    AU - Meilius, Vaidas

    AU - Didziapetriene, Janina

    AU - Matusevicius, Paulius

    PY - 2012

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    AB - Aim: Sodium valproate (NaVP) defines a novel class of histone deacetylases (HDAC) inhibitors inducing differentiation of transformed cells by their antitumor properties. Earlier we have showed that single doses of NaVP havse natriuretic, kaliuretic and chloriduretic effects in rats. The chloriduretic effect of repeated NaVP doses has not previously been investigated. The aim of the present study was to define the peculiarities of 24 h urinary chloride (Cl–) excretion in young adult Wistar rats and to evaluate the related effects of single and repeated NaVP doses in a 10-day treatment. Materials and methods: 24 h urinary Cl–, creatinine and pH levels were measured in 14 control intact Wistar male rats and 13 Wistar male rats after a single per os administration of 300 mg/kg NaVP (VP rats), 5 Wistar male rats after 10 days of the daily intragastric administration of 300 mg/kg NaVP (VP-10 rats) and 5 matched control male rats. 24 h urine was collected keeping a rat alone in a special diuresis cage (Tecniplast, Italy) for 24 h with free access to tap water, without food, in the same temperature and light conditions. 24 h urinary Cl–, Na+ levels were analyzed with an EML- 105 electrolyte analyzer (Radiometer, Denmark). Urinary pH levels were measured with a pH/mV/ion meter (ION Meter pH 340/ION, Germany). Results: After a single dose and after 10 days of NaVP administration, 24 h total diuresis and 24 h diuresis per 100 g of body weight were significantly higher in VP and VP- 10 rats as compared with the respective control. 24 h urine Cl– excretion was significantly higher in VP and VP-10 rats than in matched controls. The study data shows that repeated NaVP doses enhance Cl– excretion with urine. Authors discuss the possible new mechanism of NaVP anticancer effects related to intracellular Cl– level changes. Conclusion: The understanding of the hypothesized NaVP mechanism may lead to the recognition of Cl– as an important mediator in tumor development and as a novel therapeutic target for cancer.

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    KW - Chloride

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