Influence of Sodium Valproate on Sodium and Chloride Urinary Excretion in Rats, Gender Differences

Abstract

Evidence exists indicating that sodium valproate (VPA) increases diuresis in rats. The chloriuretic and natriuretic effect of VPA has not previously been investigated, so the aim of the present study was to define the peculiarities of 24-hour urinary sodium (Na) and chloride (Cl) excretion in young adult Wistar rats of both genders, and to evaluate the effects of VPA. 24-Hour urinary Na, Cl, creatinine and pH levels were measured in 28 control intact Wistar rats and 26 Wistar rats after a single intragastric administration of 300 mg/kg VPA. After VPA administration, 24-hour diuresis and 24-hour diuresis per 100 g of body weight were significantly higher in VPA rats of both genders. 24-Hour urine Na and Cl excretion were significantly higher in VPA male and VPA female rats than in gender-matched controls. The 24-hour urinary Cl excretion was found to be significantly higher in VPA male than in VPA female rats. The study data show that VPA, alongside the diuretic effect, enhances Na and Cl excretion with urine. The 24-hour chloriuretic response to VPA in male rats was significantly higher than in female rats. The mechanism of such a gender-related effect is not yet clear.

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

“…The specificity of valproate for GABA suggests that this interaction may be an important mechanism through which sodium valproate (NaVPA) exerts its pharmacological effects [2]. Recently NaVPA has shown to enhance the urinary excretion of sodium (Na + ) and chloride (Cl - ) ions in both genders, but the 24-h chloriduretic response in male rats to NaVPA was significantly higher than in female rats [3]. The effect of NaVPA on potassium ion (K + ) excretion was not yet studied.…”

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

“…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).…”

“…0231; 09-07-2012). The VPA dose was chosen according to literature data on preclinical pharmacodynamic studies of VPA and our own data (Ahmad et al, 2005;Grikiniene et al, 2005;Haley et al, 2005).…”

“…To exclude the influence of gonadal hormones on thymus involution, castrated male and female rats were studied also. Our hypothesis was based on the previous investigation in which VPA has been 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). Chloride plays an important role in cell proliferation: 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).…”

Gender difference in valproic acid-induced neuroprotective effects on APP/PS1 double transgenic mice modeling Alzheimer's disease

“…Our previous results suggested that VPA can decrease APP metabolism in Aβ generation, inhibit SP formation, improve spatial learning, and reduce memory defects in male AD mice [24][25][26]. Evidence indicates that there are genderrelated effects of VPA on sodium and chloride urinary excretion in rats [27] or magnesium urinary excretion in adolescents [28]. The mechanisms of such gender-related differences are not yet clear.…”