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A Anadon

Publications and source records attributed to A Anadon.

4 recordsLinked to original sources

Toxicokinetics and oral bioavailability of fumonisin B1.

The kinetics of fumonisin B1 (FB1) after single doses of 10 mg FB1/kg (po) or 2 mg FB1/kg (i.v.) were studied in male Wistar rats. Serial blood samples were obtained after p.o and i.v. administration. Liver and kidney tissue samples were also obtained after p.o administration. Plasma, liver and kidney concentrations of FB1 were determined by a reversed-phase high-performance liquid chromatographic assay using precolumn 0-phthaldialdehyde derivatisation with fluorescence detection. The FB1 plasma profile could be adequately described by a 2-compartment open model. For FB1, the elimination half-life from plasma was 1.03 h after i.v. and 3.15 h after p.o administration. The apparent volume of distribution and volume of distribution at steady state for FB1 were 0.11 and 0.072 L, respectively, after i.v. administration. The total plasma clearance of FB1 was the same for both the p.o and i.v. routes, 0.072 L/h. After the single p.o dose, FB1 was rapidly absorbed with a Tmax of 1.02 h. The maximum plasma concentration of FB1 was 0.18 microgram/mL. The p.o bioavailability of FB1 was 3.5%. The tissue concentration time data for FB1 fit a 1-compartment open model. Considerable concentrations of FB1 were found in the liver and kidney tissues. The elimination half-lives for FB1 were longer for liver (4.07 h) and kidney (7.07 h) than for plasma (3.15 h). Tissue accumulation of FB1 was evidenced by the tissue/plasma area under the concentration-time curve (AUC) ratios; the AUCtissue/AUCplasma for FB1 was 2.03 in liver and 29.89 in kidney.

Administration, Oral↗

Effects of menadione on the cardiovascular system.

Cardiotoxic mechanisms induced by anthracyclines are not clearly determined. A possible hypothesis is free radical formation and cell damage due to the quinone part of the molecule. We have studied the effect of menadione on myocardial structure and function. The effect on the red blood cells has been also determined. Groups of rats were treated orally with increasing doses (5 mg/kg/d, increased to 20 mg/kg/d and 40 mg/kg/d in the 3rd and 5th w, respectively). Duration of treatment was 6 w. ECG and blood pressure changes and blood cell count, including Heinz-Ehrlich bodies and reticulocytes, hemoglobin and hematocrit, were determined before and after treatment weekly and every 2 w, respectively. At the end of the experiment, the hearts of 2 rats/group were processed for electron microscopy. Heart, spleen and liver weights were determined. Heart, spleen, liver and kidney were subjected to histopathological examinations. Menadione treatment did not affect growth. No significant ECG changes were obtained; only significant changes of wave amplitude were observed. Menadione caused no relevant hematological changes but there were some blood pressure alterations. Morphological changes in myocardial tissue were observed including a small disorganization of myofibrils and mitochondria crystolisis. Z-lines appear forming zigzags. There were differences in organ weights. This study showed the damage induced by menadione was less than injury induced by anthracyclines.

Animals↗

Microsomal enzyme induction by permethrin in rats.

The synthetic pyrethroid, permethrin, was evaluated for its ability to alter hepatic microsomal drug-metabolizing function. The influence of permethrin (25:75 cis-trans) on plasma antipyrine kinetics and gamma-glutamyl transpeptidase (gamma-GTP) activity were studied in rats. After 3 days of administration of 90 mg permethrin/kg/day, there was no significant change in the antipyrine half-life and the area under the curve, while the apparent volume of distribution and clearance were significantly increased. Treatment with 190 mg permethrin/kg/day for 3 days decreased antipyrine half-life and the area under the curve, and increased the apparent volume of distribution and the clearance significantly. The gamma-GTP activity was significantly increased within 21 days and 14 days after the start of permethrin administration, at doses of 90 and 190 mg permethrin/kg/day, respectively. The antipyrine kinetics results indicate that permethrin is capable of producing a dose-dependent marked enzyme-inducing effect.

Animals↗