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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.


Histopathology of paraffin sections by H&E staining.Tissues were collected 15 days after the first administration of 200 mg/kg Na-DHA, after blood had been taken from the abdominal aorta of rats anesthetised using 2% pentobarbital sodium. (A) Normal control (200×); (B) (200×) and (400×), 200 mg/kg Na-DHA group; a, liver; b, kidney; c, lung; d, heart; e, stomach; f, intestine; g, spleen.
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f6: Histopathology of paraffin sections by H&E staining.Tissues were collected 15 days after the first administration of 200 mg/kg Na-DHA, after blood had been taken from the abdominal aorta of rats anesthetised using 2% pentobarbital sodium. (A) Normal control (200×); (B) (200×) and (400×), 200 mg/kg Na-DHA group; a, liver; b, kidney; c, lung; d, heart; e, stomach; f, intestine; g, spleen.

Mentions: Occasionally, haemorrhage could be observed by the naked eye in subcutaneous tissue and the liver surface. H&E staining of the tissues of rats treated with 200 mg/kg Na-DHA are shown in Fig. 6, congestion or haemorrhage in tissues was observed. H&E staining also revealed: congestion in hepatic sinusoids, renal tubules and spleen; slight haemorrhage in lung alveoli and intestinal mucosa; considerable haemorrhage in the gastric mucosa and cardiac muscle cells. There was not clear difference between males and females with respect to congestion or haemorrhage of these tissues. Severe haemorrhage was not observed in these organs. Similar congestion or haemorrhage of these tissues was observed upon administration of 50–150 mg/kg of Na-DHA.


Serum pharmacokinetics and coagulation aberration induced by sodium dehydroacetate in male and female Wistar rats
Histopathology of paraffin sections by H&E staining.Tissues were collected 15 days after the first administration of 200 mg/kg Na-DHA, after blood had been taken from the abdominal aorta of rats anesthetised using 2% pentobarbital sodium. (A) Normal control (200×); (B) (200×) and (400×), 200 mg/kg Na-DHA group; a, liver; b, kidney; c, lung; d, heart; e, stomach; f, intestine; g, spleen.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Histopathology of paraffin sections by H&E staining.Tissues were collected 15 days after the first administration of 200 mg/kg Na-DHA, after blood had been taken from the abdominal aorta of rats anesthetised using 2% pentobarbital sodium. (A) Normal control (200×); (B) (200×) and (400×), 200 mg/kg Na-DHA group; a, liver; b, kidney; c, lung; d, heart; e, stomach; f, intestine; g, spleen.
Mentions: Occasionally, haemorrhage could be observed by the naked eye in subcutaneous tissue and the liver surface. H&E staining of the tissues of rats treated with 200 mg/kg Na-DHA are shown in Fig. 6, congestion or haemorrhage in tissues was observed. H&E staining also revealed: congestion in hepatic sinusoids, renal tubules and spleen; slight haemorrhage in lung alveoli and intestinal mucosa; considerable haemorrhage in the gastric mucosa and cardiac muscle cells. There was not clear difference between males and females with respect to congestion or haemorrhage of these tissues. Severe haemorrhage was not observed in these organs. Similar congestion or haemorrhage of these tissues was observed upon administration of 50–150 mg/kg of Na-DHA.

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–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.