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

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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.

No MeSH data available.


Effect on APTT in rats treated with Na-DHA.Wistar rats were administered Na-DHA at different doses for 13 days by lavage. APTT values were measured at different times by an automated blood coagulation analyser. (A) Male; (B) female.  Control,  50 mg/kg;  100 mg/kg;  150 mg/kg;  200 mg/kg. ***p < 0.0 01, significantly different from controls.
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f2: Effect on APTT in rats treated with Na-DHA.Wistar rats were administered Na-DHA at different doses for 13 days by lavage. APTT values were measured at different times by an automated blood coagulation analyser. (A) Male; (B) female. Control, 50 mg/kg; 100 mg/kg; 150 mg/kg; 200 mg/kg. ***p < 0.0 01, significantly different from controls.

Mentions: Data for PT and APTT in rats treated with different doses of Na-DHA are shown in Figs 1 and 2. PT and APTT were prolonged significantly in each rat of 50, 100, 150 and 200 mg/kg groups at each time point post-administration (p < 0.001). There was no clear relationship in dose via PT or time via PT, and there was no clear difference in PT, between males and females.


Serum pharmacokinetics and coagulation aberration induced by sodium dehydroacetate in male and female Wistar rats
Effect on APTT in rats treated with Na-DHA.Wistar rats were administered Na-DHA at different doses for 13 days by lavage. APTT values were measured at different times by an automated blood coagulation analyser. (A) Male; (B) female.  Control,  50 mg/kg;  100 mg/kg;  150 mg/kg;  200 mg/kg. ***p < 0.0 01, significantly different from controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384240&req=5

f2: Effect on APTT in rats treated with Na-DHA.Wistar rats were administered Na-DHA at different doses for 13 days by lavage. APTT values were measured at different times by an automated blood coagulation analyser. (A) Male; (B) female. Control, 50 mg/kg; 100 mg/kg; 150 mg/kg; 200 mg/kg. ***p < 0.0 01, significantly different from controls.
Mentions: Data for PT and APTT in rats treated with different doses of Na-DHA are shown in Figs 1 and 2. PT and APTT were prolonged significantly in each rat of 50, 100, 150 and 200 mg/kg groups at each time point post-administration (p < 0.001). There was no clear relationship in dose via PT or time via PT, and there was no clear difference in PT, between males and females.

View Article: PubMed Central - PubMed

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&ndash;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&ndash;200&thinsp;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.

No MeSH data available.