Abstract
Valproic acid (VPA) has been demonstrated to exhibit anti-diabetic effect and attenuate hypertensive responses in animal models but its safety evaluation on the kidney has not been reported. This study investigated the effect of VPA on selected kidney function indices of rats. Twenty healthy Wistar rats were randomly grouped into 4 of 5 rats each. Rats in group 1 (control) were administered clean water only, while rats in groups 2, 3 and 4 were administered 100, 300 and 600 mg/kg body weight (bw) of VPA, respectively for 3 weeks. Serum concentrations of creatinine, urea, sodium, potassium, phosphate and chloride ions as well as the activities of alkaline phosphatase (ALP), acid phosphatase (ACP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the kidney and serum of rats were determined. VPA at the 3 doses administered did not significantly affect (p>0.05) the kidney/body weight ratio, serum concentrations of creatinine, urea, sodium ion and phosphate ion when compared with control. VPA at 600 mg/kg bw alone and at both 300 and 600 mg/kg bw significantly increased (p<0.05) the serum levels of potassium and chloride ions, respectively. VPA did not significantly affect (p>0.05) the kidney ALP and ALT activities as well as the serum ALP, ACP, AST and ALT activities but significantly increased (p<0.05) the kidney ACP and AST activities at 300 mg/kg bw. These results imply that treatment with VPA at higher doses may adversely affect the reabsorption of chloride ion in the kidney which may alter the acid/base balance and impair nerve impulse transmission.
Highlights
Valproic acid (2-propylvaleric acid or 2propylpentanoic acid), a derivative of valeric acid, is a branched short-chain fatty acid forming a clear liquid at room temperature with half-life of 9 to 16 hours (Soori et al, 2015)
Valproic acid (VPA) at all the treatment doses (100, 300 and 600 mg/kg bw) administered did not significantly affect (p>0.05) the kidney/body weight ratio of rats when compared with control (Table 1)
VPA at the 3 doses administered did not significantly affect (p>0.05) serum concentrations of creatinine and urea when compared with control (Table 2)
Summary
Valproic acid (2-propylvaleric acid or 2propylpentanoic acid), a derivative of valeric acid, is a branched short-chain fatty acid forming a clear liquid at room temperature with half-life of 9 to 16 hours (Soori et al, 2015). Valproic acid (VPA) is quickly metabolized in the liver, and the various metabolites resulting from the metabolism are pharmacologically active. Valproic acid is generally used in clinics as an antiepileptic drug and for the treatment of bipolar disorders and migraine prophylaxis (Kostrouchova et al, 2007). It is extensively metabolized by microsomal glucuronide conjugation, mitochondrial beta-oxidation and cytochrome P450dependent omega (omega–1 and omega–2) oxidation (Perucca, 2002). The pharmacological effects of VPA involve increased gamma-
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