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

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. [...].