Serum pharmacokinetics and coagulation aberration induced by sodium dehydroacetate in male and female Wistar rats

Abstract

Sodium dehydroacetate (Na-DHA) is used as a preservative in food, animal feeds and cosmetics. Severe haemorrhage in organs and prolongation of coagulation factors in Sprague-Dawley rats has been reported upon oral administration of Na-DHA. We investigated alterations in coagulation parameters and serum pharmacokinetics upon Na-DHA administration. Wistar rats were administered Na-DHA (50-200 mg/kg, p.o.). Weight gain, food consumption, prothrombin time (PT), activated partial thromboplastin time (APTT), serum levels of Vitamin K (Vk)1, and serum levels of Na-DHA were measured, and histopathology undertaken. Significant reductions in body weight, food consumption and serum levels of Vk1, as well as prolonged PT and APTT, were observed. Females were significantly different from males in terms of serum Na-DHA concentration. Congestion in hepatic sinusoids, renal tubules and spleen, as well as haemorrhage in lung alveoli, gastric mucosa, intestinal mucosa and cardiac muscle cells, were observed by histopathological analyses. Correlation of serum Na-DHA via PT and APTT, as well as serum Vk1 via PT and APTT, in females was better than that in males. Female rats are more sensitive than males to Na-DHA. Hence, Na-DHA can induce coagulation aberration in Wistar rats, with higher sensitivity seen in females than males.