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.
Highlights
Sodium dehydroacetate (Na-DHA) is used as a preservative in food, animal feeds and cosmetics
Warfarin has the structure of coumarin (4-hydroxy-2-pyrone), and it has been reported that some derivatives of 4-hydroxy-2-pyrone have anticoagulant activity in rats[17]
We investigated the effect of repeated administration of Na-DHA to Wistar rats on changes in body weight, food consumption, parameters of blood coagulation, prothrombin time (PT) and activated partial
Summary
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. Na-DHA can induce coagulation aberration in Wistar rats, with higher sensitivity seen in females than males. Na-DHA is classified as ‘toxic’ or ‘harmful’ only for products for use around the mouth/lips by the European Union (EU)[4], and is designated as ‘safe’ for general or specific, limited use in food or cosmetics by the EU and US Food and Drug Administration[4,5,6]. Sakaguchi et al.[14] reported that repeated oral administration of Na-DHA in male Sprague–Dawley (SD) rats induced severe haemorrhage in multiple organs and prolongation of blood coagulation factors (BCFs). We investigated the effect of repeated administration of Na-DHA to Wistar rats on changes in body weight, food consumption, parameters of blood coagulation, prothrombin time (PT) and activated partial www.nature.com/scientificreports/
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