Absorption,metabolism and excretion of 3-acetyl don in pigs

The absorption, metabolism and excretion of 3-acetyldeoxynivalenol (3-aDON) in pigs were studied. Pigs with a faecal microflora known to be able to de-epoxidate trichothecenes were used in the experiment. The pigs were fed a commercial diet with 3-aDON added in a concentration of 2.5 mg/kg feed for 2.5 days. No traces of 3-aDON or its de-epoxide metabolite were found in plasma, urine or faeces. Deoxynivalenol (DON) was detected in plasma as soon as 20 min after start of the feeding. The maximum concentration of DON in plasma was reached after 3 h and decreased rapidly thereafter. Only low concentrations close to the detection limit were found in plasma 8 h after start of the feeding. A significant part of the DON in plasma was in a glucuronide-conjugated form (42 ± 7%). No accumulation of DON occurred in plasma during the 60 h of exposure. The excretion of DON was mainly in urine (45 ± 26% of the toxin ingested by the pigs) and only low amounts of metabolites of 3-aDON (2 ± 0.4%) were recovered in faeces. De-epoxide DON constituted 52 ± 15% of the total amount of 3-aDON-metabolites detected in faeces. The remaining part in faeces was DON. DON was still present in the urine and faeces at the end of the sampling period 48 h after the last exposure. The results show that no de-epoxides are found in plasma or urine in pigs after trichothecene exposure, even in pigs having a faecal microflora with a de-epoxidation activity. The acetylated form of the toxin is deacetylated in vivo. Furthermore, the experiment shows that the main part of DON is rapidly excreted and does not accumulate in plasma, but a minor part of the toxin is retained and slowly excreted from the pigs.     

Distribution, metabolism and excretion of [1-14C]dolichol injected intravenously into rats.

[1-14C]Dolichol mixed in vitro with rat serum and injected intravenously into rats was rapidly cleared from the circulation in a manner consistent with a two-compartment model. About 80% of the radioactivity recovered from animals killed after 1 day was in the liver, with smaller amounts being found in lung, carcass (internal organs removed), gastrointestinal tract and contents, and spleen. The kidneys, testes and heart contained little radioactivity, and the brain did not appear to take up any [1-14C]dolichol. The half-life for the turnover of radioactivity from [1-14C]dolichol in tissues varied considerably, being 2 days for the lung, 17 for liver and about 50 days for the carcass. After 1 day, and also after 4 and 21 days, most of the radioactivity in all tissues was as [1-14C]dolichol and as [1-14C]dolichyl fatty acyl ester, although a small amount of incorporation of [1-14C]dolichol radioactivity into phospholipids was also observed. Faeces collected over the first 4 days after injection contained 13% of the [1-14C]dolichol dose, but urine and expired air contained only small amounts of radioactivity. Radioactivity in faeces was nearly all as unchanged [1-14C]dolichol and as [1-14C]dolichyl fatty acyl ester. The [1-14C]dolichol remaining in liver after 21 days appeared to be in a pool (possibly lysosomes) where most of it was not subject to excretion.     

(14C)Ethylenethiourea: distribution, excretion, and metabolism in pregnant rats.

Following administration of single oral doses of [14C]ethylenethiourea (ETU) to pregnant rats maternal blood maintained peak radioactivity for 2 h, and the radioactivity was dispersed uniformly between the red blood cells and plasma. The level of radioactivity was distributed equally among several maternal tissues but was present in lower amounts in embryos. Twenty-four hours after treatment all tissues examined, except blood, were relatively clear of radioactivity and 72.8% of the total radioactivity given had been excreted in the urine. Elution patterns of metabolites from Sephadex separation suggested that ethylenethiourea was degraded very little. The teratological mechanism is discussed.     

Sulfur containing acyclovir derivatives: synthesis, cytotoxic activity, and cell phenotype studies

New 2-amino-6-oxo-8-thioxo-9-substituted purine derivatives were prepared and assayed for the in vitro cytotoxic activity. Some products exhibited moderate activity on HT-1080 cells and rather high activity on MG-22A cells.     

Steroid metabolism in the cat. Biliary and urinary excretion of metabolites of [4-14C]oestradiol

1. [4-¹⁴C]Oestradiol was administered to seven male, seven female and two castrated male cats as a single intravenous injection. Bile and urine were collected for 6h. 2. The radioactivity was excreted mainly in the bile of all animals (53–60%); only approx. 1% of the dose appeared in the urine. 3. Bile and urine samples were hydrolysed successively by β-glucuronidase, cold acid and hot acid. There were significant differences (P<0.005) between the percentage of the dose present in the bile fractions hydrolysed by β-glucuronidase (male, 9.0±1.7%; female, 18.6±1.45%) and by cold acid (male, 18.9±1.44%; female 12.1±1.02%). The excretion of radioactivity in these fractions by the castrated male cats was closer to that of female cats. 4. Approx. 20–27% of the dose could not be extracted from aqueous solution (pH10.5) by ethyl acetate–ether after hydrolysis.     

Steroid metabolism in the cat. Biliary and urinary excretion of metabolites of [4-14C]cortisone

1. [4-(14)C]Cortisone was administered to anaesthetized male cats as a single injection or as a 45-60min. infusion. 2. After the single dose a total of 69.6-89.6% of the radioactivity was excreted in bile, and 0.5-7.1% in urine. After infusion total recovery in bile was 73.4-92.1%, and 1.2-1.7% in urine. 3. When bile and urine samples were hydrolysed successively by beta-glucuronidase, cold acid and hot acid, most of the radioactivity was converted into substances not extractable from neutral aqueous solution by ethyl acetate-ether. 4. In bile, metabolites hydrolysable by beta-glucuronidase were found in only small proportions (3-4%) of the dose.     

Steroid metabolism in the cat. Biliary and urinary excretion of metabolites of [4-14C]testosterone

1. [4-(14)C]Testosterone was administered intravenously to anaesthetized male cats as a single injection or as a 45-60min. infusion. 2. Most of the administered radioactivity was excreted in the bile (70-80%); only 2.9-5.5% of the dose was excreted in the urine. 3. Bile and urine samples were hydrolysed successively to yield glucuronide, ;cold-acid-hydrolysed' and ;hot-acid-hydrolysed' fractions. 4. The proportion of glucuronides in bile decreased in successive samples, but cold-and hot-acid-hydrolysed metabolites showed no consistent change. 5. After hydrolysis most of the radioactivity in both bile and urine could not be extracted by ether from neutral aqueous solution.     

Steroid metabolism in the rabbit. Biliary and urinary excretion of metabolites of [4-14C]progesterone

1. [4-(14)C]Progesterone was administered intravenously to anaesthetized male and female New Zealand White rabbits as a single injection or as a 45-60min. infusion. 2. After a single dose about 60% of the radioactivity was recovered in 6hr., and twice as much radioactivity was present in bile as in urine. After infusion total recovery of radioactivity was only about 40% in 6hr., but the relative proportions of metabolites in bile and urine were about the same as after a single dose. 3. Bile and urine samples were hydrolysed successively by beta-glucuronidase, cold acid and hot acid. 4. In bile the major proportion of metabolites appeared in the glucuronide fraction; in urine beta-glucuronidase hydrolysis yielded the greatest amounts of ether-extractable radioactivity, but the greatest proportion of radioactivity could not be extracted by ether from an alkaline solution of the hydrolysed urine. 5. There was no apparent difference in the quantity or distribution of metabolites excreted by male and female animals.