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Biomedical subjects

A W Hayes

Publications and source records attributed to A W Hayes.

At least 55 records · Page 3Linked to original sources
PubMed1982

Embryocidal, teratogenic and fetotoxic effects of citrinin in rats.

Citrinin, a fungal metabolite produced by several species of Penicillium and Aspergillus, has been found to contaminate foods used by animals and man. Citrinin is nephrotoxic and has been implicated in disease outbreaks in animals and humans. In this study the teratogenicity, embryotoxicity, and fetotoxicity of citrinin was determined in Sprague-Dawley rats after subcutaneous administration of a single dose of 35 mg/kg on gestation day 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. Dams so treated lost weight for 2 days following administration. Subsequently, weight gain for treated animals was similar to that for controls. Relatively high maternal mortalities also were associated with this pretreatment regimen. Treatment with 35 mg/kg on certain days of gestation resulted in deaths of one half or more of the pregnant dams. No significant effects of citrinin were observed on the number of implants. Resorption of implants, however, was higher in treated animals than controls when dams were treated on days 6, 7, 8, 10, 11 or 12 of gestation. Fetuses from dams given citrinin were significantly smaller than those from controls by about 22% on average. No major gross or skeletal malformations were found in fetuses born to mothers which received citrinin. Major internal soft tissue malformations seen were enlarged kidneys, internal hydrocephalus and cleft palate.

Animals↗
PubMed1982

Disposition and metabolism of [14C]citrinin in pregnant rats.

Citrinin is a product of fungal metabolism capable of producing nephrotoxicity. Distribution, excretion and metabolism of [14C]citrinin was studied in pregnant female rats after subcutaneous administration of 35 mg/kg on the 12th day of gestation. Elimination of [14C]citrinin-derived radioactivity from plasma was biphasic. The half-lives for the rapid (alpha) and slower (beta) phases of elimination were 1.95 h and 39.7 h, respectively. Approximately 74% of the radioactivity appeared in the urine in the first 24 h, with only 1.7% and 1.4% in the urine at 48 h and 72 h, respectively. Fecal elimination accounted for 9.5%, 4.1% and 7.3% of the total radioactivity at each of these times. At least one metabolite of citrinin was demonstrable with high performance liquid chromatography (HPLC) of plasma extracts. Retention times for the parent compound and metabolite were 270 s and 175 s, respectively. The metabolite was more polar than the parent compound. At least 2 metabolites of citrinin were found in urine of the same rats. Retention times for two metabolites were 140 s and 180 s, with both metabolites more polar than the parent compound. Chromatograms of bile samples suggested at least one metabolite was present with a retention time of 140 s. Chromatograms of uterus extracts indicated the presence of one metabolite with a retention time of 180 s. Chromatograms of fetus extracts indicated that no metabolites of citrinin were present.

Animals↗
PubMed1982

Embryocidal, fetotoxic and teratogenic effects of ochratoxin A in rats.

Teratogenic effects of a single subcutaneous dose of ochratoxin A (1.75 mg/kg) on one of gestation days 4-10 has been studied in rats. Treatment on days 4, 5, 6 or 7 resulted in increased fetal resorptions, and decreased fetal weights. Fetal weights also were depressed after treatment on day 8. The highest number of resorptions, greatest depression of fetal weights and largest number of malformations occurred when ochratoxin A was injected on days 5, 6 or 7. External hydrocephaly, omphalocele, and anophthalmia were the major gross anomalies. Internal hydrocephaly and shift in position of esophagus were the main internal soft tissue defects. Major skeletal defects involved sternebrae, vertebrae and ribs. Subcutaneous injection of 1.75 mg/kg ochratoxin A seemed to be the minimum effective, single teratogenic dose. Lower doses (0.5 or 1.0 mg/kg) failed to produce any embryotoxicity or malformations and higher doses (e.g. 5.0 mg/kg) caused all fetuses to be resorbed.

Animals↗
PubMed1982

Teratogenicity of secalonic acid D in rats.

Teratogenic effects of secalonic acid D (SAD), a toxic fungal metabolite, produced by P. oxalicum has been studied in rats. Crystalline SAD was injected as a single subcutaneous dose (25 mg/kg) on one of the gestation day 6-10, 12 or 14. Pregnant rats were treated with 15 mg/kg SAD on gestation day 10. Both doses produced teratogenic and fetotoxic effects, although the effects produced with the lower dose were less marked. Treatment on days 9 and 10 resulted in increased fetal resorptions and decreased fetal body weights. The highest number of resorptions, greatest depression of fetal body weights and largest number of malformations occurred when SAD was injected on day 10. Anophthalmia (days 9 and 10), exencephaly (day 9) and defects in limbs, digits and tail (day 10) were the major gross malformations. The main internal soft tissue defects were hydronephrosis (days 9 and 10) and tracheo-esophageal fistula and renal agenesis (day 10). Major skeletal defects involved the vertebrae and ribs. For all of the abnormalities observed, administration of SAD on day 10 of gestation produced the most marked effects in rats.

Abnormalities, Drug-Induced↗
PubMed1982

In vitro metabolism of penicillic acid with mouse-liver homogenate fractions.

The metabolism of penicillic acid (PA), a carcinogenic mycotoxin, was studied in vitro using subcellular fractions of mouse-liver homogenates. PA reacted with glutathione (GSH) both enzymatically and non-enzymatically. Each reaction was of equal importance. The in vitro metabolism of PA using different hepatic subcellular fractions was essentially non-enzymatic when GSH was absent, but metabolism was strikingly increased when GSH was available. In the microsomal preparation in the presence of GSH 75% of the added PA was biotransformed within 30 min to metabolite(s) that were not extractable with organic solvents. HPLC analysis indicated that the metabolite(s) were more polar than the parent compound.

Animals↗
PubMed1982

Vanadium-induced inhibition of renal Na+, K+-adenosinetriphosphatase in the chicken after chronic dietary exposure.

Recent work has shown that V accumulates in the kidney and is a potent inhibitor of Na+, K+-adenosinetriphosphatase (ATPase) in vitro. Thus, as a nutritionally required element, V may regulate cation transport. The effect of chronic intake of the metal on Na+, K+-ATPase in vivo has not been reported. In this study laying strain chickens were fed calcium orthovanadate for 15 mo from d 1 of age at levels of 0, 25, 50, and 100 ppm in the diet. Whole tissue homogenates and 13,000 X g fractions were analyzed for ATPase activities. Concentrations of V producing 50% inhibition of Na+, K+-ATPase activity ranged from 1.0 X 10(-5) M in liver to 1.8 X 10(-6) M in kidney, which was the most sensitive tissue tested in vitro. Mg2+ -ATPase was more resistant to V than Na+, K+-ATPase. Studies in vivo suggested a V-dependent inhibition of renal Na+, K+-ATPase. Correlation of enzyme specific activity and levels of V in kidneys suggested V-ATPase mediated alteration in renal function.

Adenosine Triphosphatases↗
PubMed1982

High pressure liquid chromatographic determination of aflatoxins by using radial compression separation.

A rapid method for the determination of aflatoxins was developed using high pressure liquid chromatography and a radial compression separation system. A standard solution of aflatoxins B1, B2, G1, G2, and M1 was analyzed solution of aflatoxins B1, B2, G1, G2, and M1 was analyzed at flow rates of 2.0 and 6.0 mL/min. Retention times, peak heights, and peak areas were reproducible over a 3-day period. Coefficients of variation for aflatoxin B1 at 2.0 and 6.0 mL/min were, respectively, 1.04 and 0.87% (retention time); 2.9 and 4.7% (peak height); and 8.2 and 4.7% (peak area). At 6.0 mL/min there was an approximate 25% loss in sensitivity but a greater than 50% reduction in retention time. Separation of all the aflatoxins was excellent using a dual flow rate of 2.0 mL/min with a change to 8.0 mL/min at 15 min post-injection. The applicability of the radial compression separation system for the rapid determination of aflatoxins in human tissues was also tested. Spiked samples of liver, serum, and urine-showed good resolution of all aflatoxin peaks at the higher flow rates.

Aflatoxins↗
PubMed1981

High-performance liquid chromatographic analysis of the mycotoxin secalonic acid D and its application to biological fluids.

Secalonic acid D (SAD) is an acutely toxic, teratogenic and possibly mutagenic fungal metabolite produced in corn by Penicillium oxalicum. Using ultraviolet absorbance at 340 nm as a means of detection, SAD was resolved as a sharp peak by reversed-phase high-performance liquid chromatography (HPLC) on a small particle (10 mu m) mu Bondapak C18 column in 4 min by an acetonitrile--water--glacial acetic acid-tetrahydrofuran (5:3:0.5:0.5 for solvent system A and 4:3:0.5:0.5 for solvent system B) elution solvent system. The flow-rates for the two solvent systems (A and B) were 1.5 and 1.7 ml/min; column operating pressures of 1500 and 1800 p.s.i., respectively, resulted. The relationship between peak height or peak area and the quantity of SAD injected was linear over a range of 1--50 ng. Detection was very sensitive with lower limits of detection of 0.6 and 0.7 ng of SAD in solvent systems A and B, respectively. Retention times, peak heights and peak areas were highly reproducible in both solvent systems. Detection of SAD in spiked (0.2--10 mu g/ml) urine and bile samples injected without cleanup onto the HPLC column and quantitative extraction of SAD by ethyl acetate from spiked, acidified plasma samples (0.1--5 mu g/ml) followed by HPLC analysis were obtained. Solvent system B gave better resolution of SAD from the interfering substances in bile and urine than solvent system A. However, sensitivity was slightly greater in solvent system A.

Bile↗
PubMed1981

Evaluation of renal function in saccharin treated rats.

Renal function and transport have been examined in male and female rats at various times during a 6-month exposure to sodium saccharin. The animals were maintained on special diets containing 0%, 1%, 5% or 7.5% sodium saccharin. Developmental patterns for renal transport and renal function in the control animals were normal. The 5% and 7.5% concentrations of saccharin caused a reduction in the renal slice steady-stable accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) which became significant after the animals were 30 days of age or older. Enhanced sodium excretion was observed in every age group of animals tested when these animals consumed sodium saccharin concentrations greater than or equal to 1% in the diet. At 60 days of age, increased urine volume, a decrease in urine osmolality, and increased potassium excretion were also found. All effects of saccharin on renal function and transport were promptly and completely reversible when the animals were removed from the saccharin diet for as little as 24 h. The effects of saccharin on PAH transport apparently were attributable to competitive inhibition. Although effects on TEA transport and other renal function parameters were not defined as to mechanism, the effects were as readily reversible as those on PAH when saccharin was removed from the diet.

Animals↗
PubMed1981

Effect of penicillic acid on biliary excretion of indocyanine green in the mouse and rat.

Penicillic acid (PA), a mycotoxin, is hepatotoxic. A study was undertaken to investigate its effects on hepatobiliary excretory function, using the anionic compounds indocyanine green (ICG), in mice and rats. Pretreatment with a single dose of PA (90 mg/kg, ip, an LD50 dose in both species) resulted in depression of ICG excretion in both species. This depression was dose- and time-dependent. Decreases of 42 and 57% in biliary excretion of ICG were observed in rats and mice 48 and 72 h after PA pretreatment, respectively. Although bile flow was depressed significantly when expressed in terms of body weight, it was not altered in mice when expressed in terms of liver weight. Bile flow was not affected in rats. While the serum ICG concentration was increased after PA treatment in both species, the liver ICG concentration was not affected. The liver-to-serum, bile-to-serum, and bile-to-liver ICG concentration ratios decreased in PA-treated animals. These data suggest that the PA-induced hepatobiliary excretory dysfunction may result from depression of both uptake of ICG into the liver and bile canlicular transport of ICG.

Animals↗
PubMed1981

High pressure liquid chromatographic determination of penicillic acid in chicken tissues.

Penicillic acid (PA) is a mycotoxin with reported cytotoxic, cardiotoxic, and carcinogenic activity and it can occur in high concentration in corn. The occurrence of PA in contaminated poultry feed represents a potential public health hazard. A reverse phase high pressure liquid chromatographic (HPLC) method is proposed for determining PA residues in chicken tissues. Optimization of chromatography was achieved for PA using a mobile phase consisting of acetonitrile: H2O. PA was detected by ultraviolet absorption at 254 nm, identified by retention time, and quantitated by peak area integration. Blood, parenchymal tissues, muscle, and alimentary tract contents were homogenized, sonicated, and acid treated followed by extraction with ethyl acetate and analysis by HPLC. Acute oral dosing of chickens with PA over a range of 50 to 550 mg/kg body weight resulted in detectable levels of the mycotoxin (confirmed by gas liquid chromatography) in gizzard muscle and contents, liver, kidney, heart, and intestinal contents. This method should prove useful both for the rapid and sensitive detection of PA residues in poultry and in further studies on the distribution and metabolism of this mycotoxin.

Animals↗
PubMed1980

High-performance liquid chromatographic analysis of the mycotoxin penicillic acid and its application to biological fluids.

Penicillic acid (PA) is a carcinogenic food contaminant produced by several food-borne fungi. PA was resolved as a sharp peak by reversed-phase high-performance liquid chromatography on a small-particle (10 micrometer) column in 3-4 min by an elution system composed of acetonitrile (AN), water and glacial acetic acid (AC) with detection by ultraviolet (UV) absorbance at 254 nm. Peak height and peak area were related linearly to the amount of PA injected over a range of 5-500 ng. Reproducibility of retention time, peak height and peak area was demonstrated. The lower detection limit was 5 ng in two elution systems [AN-H2O-AC(45:55:2), flow-rate (F) 1 ml/min; AN-H2O-AC(40:60:2), F = 1.2 ml/min] and 10 ng in a third system [AN-H2O-AC(25:75:2), F = 1.6 ml/min]. Based on the sensitivity and separation of PA from (40:60:2), F = 12 ml/min; urine, AN-H2O-AC (25:75:2), F = 1.6 ml/min. Good recovery (89-98%) over a range of 1-50 microgram/ml of PA was obtained from PA-spiked plasma samples treated first with 25% HPO3 followed by extraction with chloroform. A single peak detected either by UV absorbance or by radioactivity was obtained when plasma samples spiked with [14C]PA were extracted. Good recovery (92-105%) of PA also was obtained from spiked urine and bile samples.

Caproates↗