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

Background: The diuretic effect of valproates and its relation to urinary potassium (K+) and chloride (Cl-) excretion have not yet been investigated, so the aim of this study was to evaluate the influence of a single dose of sodium valproate (NaVPA) on 24-h urinary K+ and Cl- excretion in young adult Wistar rats of both genders. For measurement of K+ in urine, the same animals and samples as in our earlier publication were used (Pharmacology 2005 Nov, 75:111–115). The authors propose a new approach to the pathophysiological mechanisms of NaVPA effect on K+ and Cl- metabolism. Twenty six Wistar rats were examined after a single intragastric administration of 300 mg/kg NaVPA (13 NaVPA-male and 13 NaVPA-female), 28 control intact Wistar rats (14 males and 14 females) were studied as a control group. The 24-h urinary K+, Cl-, creatinine and pH levels were measured. Results: Total 24-h diuresis and 24-h diuresis per 100 g of body weight were found to be significantly higher in NaVPA-rats of both genders than in rats of the control group (p 0.05). 24-h urinary K+ excretion per 100 g of body weight in NaVPA-male rats was significantly higher than in control males (p = 0.025). NaVPA enhanced Cl- urinary excretion: 24-h Cl- urinary excretion, 24-h urinary Cl- excretion per 100 g of body weight and the Cl-/creatinine ratio were significantly higher in NaVPA-male and NaVPA-female rats than in gendermatched controls (p < 0.05). 24-h chloriduretic response to NaVPA in male rats was significantly higher than in female rats (p < 0.05). Conclusion: NaVPA causes kaliuretic and chloriduretic effects with gender-related differences in rats. Further investigations are necessary to elucidate the mechanism of such pharmacological effects of NaVPA

Investigation of Vitamin D-Binding Protein Polymorphism Impact on Coronary Artery Disease and Relationship with Longevity: Own Data and a Review

The aim of the study was to assess the effect of vitamin D-binding protein (DBP) polymorphism on coronary artery disease (CAD). DBP phenotypes were identified in the groups: control ( = 306), men suffering from CAD ( = 154), and long-lived individuals ( = 108). Isoelectric focusing of DBP phenotypes in serum was performed on polyacrylamide gel. Distribution of DBP phenotypes in the study groups was found to be in Hardy-Weinberg equilibrium. Gc1s-1s phenotype and Gc1s allele frequency in CAD groups were significantly higher than in control, and Gc1s allele frequency was found significantly more often in CAD compared with longlived group ( &lt; 0.05). The Gc2 allele frequency in control was higher as compared with Gc2 frequency in CAD group ( &lt; 0.05). The Gc2-2 phenotype was more frequent in long-lived survivors than in the CAD group ( &lt; 0.05). It was found that the Gc1s allele significantly increased the risk of CAD with the odds ratio (OR) equal to 1.45 ( &lt; 0.02) and showed Gc2 to be related with a decreased risk of CAD (OR = 0.69; &lt; 0.03). Authors review the role of DBP in resistance to atherosclerosis and cancer as the main longevity determinants

Sodium Valproate Enhances the Urethane-Induced Lung Adenomas and Suppresses Malignization of Adenomas in Ovariectomized Female Mice

In the present study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in female mice has been evaluated. BALB/c mice (n=60; 4–6 weeks old, females) were used in the following groups: (1) urethane-treated; (2) urethane-NaVP-treated; (3) only NaVP-treated; (4) control. In the same groups, ovariectomized female mice (n=60) were investigated. Urethane was given intraperitoneally, with a total dose of 50 mg/mouse. In NaVP-treated mice groups, 0.4% aqueous solution of NaVP was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in ovariectomized mice and in those treated with urethane and NaVP was significantly higher than in mice treated with urethane only (8.29±0.58 versus 6.0±0.63, p<0.02). No significant difference in the number of tumors per mouse was revealed while comparing the nonovariectomized urethane- and urethane-NaVP-treated groups (p=0.13). A significant decrease of adenocarcinoma number in ovariectomized mice treated with a urethane-NaVP as compared with ovariectomized mice treated with urethane only was found (p=0.031). NaVP together with low estrogen may have a protective effect on the malignization of adenomas in ovariectomized mice

The importance of gender-related anticancer research on mitochondrial regulator sodium dichloroacetate in preclinical studies in vivo

Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+–K+–2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed

Correlation between 24-h diuresis and Kexcretion in NaVPA male and female rats

<p><b>Copyright information:</b></p><p>Taken from "Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences"</p><p>http://www.biomedcentral.com/1471-2210/7/9</p><p>BMC Pharmacology 2007;7():9-9.</p><p>Published online 6 Aug 2007</p><p>PMCID:PMC1959196.</p><p></p> * – Statistically significant correlation

The importance of gender-related anticancer research on mitochondrial regulator sodium dichloroacetate in preclinical studies in vivo

Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+–K+–2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed

Correlation between 24-h diuresis and Clexcretion in NaVPA male and female rats

<p><b>Copyright information:</b></p><p>Taken from "Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences"</p><p>http://www.biomedcentral.com/1471-2210/7/9</p><p>BMC Pharmacology 2007;7():9-9.</p><p>Published online 6 Aug 2007</p><p>PMCID:PMC1959196.</p><p></p> * – Statistically significant correlation

Correlation between urine pH and Clexcretion in NaVPA male and female rats

<p><b>Copyright information:</b></p><p>Taken from "Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences"</p><p>http://www.biomedcentral.com/1471-2210/7/9</p><p>BMC Pharmacology 2007;7():9-9.</p><p>Published online 6 Aug 2007</p><p>PMCID:PMC1959196.</p><p></p> * – Statistically significant correlation