Search PubMed⌕ Search

Biomedical subjects

G E Rottinghaus

Publications and source records attributed to G E Rottinghaus.

At least 91 records · Page 5Linked to original sources
PubMed1991

Cytotoxicity of trichothecene mycotoxins isolated from Fusarium sporotrichioides (MC-72083) and Fusarium sambucinum in baby hamster kidney (BHK-21) cells.

Twenty-six trichothecene mycotoxins produced by Fusarium sporotrichioides (MC-72083) and Fusarium sambucinum were screened for relative cytotoxicity in cultured baby hamster kidney (BHK-21) cells. The relative cytotoxicity was measured as LC100. The most cytotoxic trichothecenes were T-2 toxin (5 ng/ml) and the recently isolated 4-propanoyl HT-2 (5 ng/ml) and 3'-hydroxy T-2 toxin (5 ng/ml). T-2 tetraol (1 x 10(4) ng/ml), 8-beta-hydroxytrichothecene (1 x 10(4) ng/ml), sporotrichiol (2 x 10(4) ng/ml), 8-oxodiacetoxyscirpenol (6 x 10(4) ng/ml) and 8-acetyl T-2 tetraol (1 x 10(5) ng/ml) were the least toxic of the regular trichothecenes. None of the modified trichothecenes or the apotrichothecene were very cytotoxic: 8-beta-hydroxysambucoin (2 x 10(3) ng/ml), FS-1 (5 x 10(3) ng/ml), 8-alpha-hydroxysambucoin (8 x 10(4) ng/ml) and trichotriol (1 x 10(5) ng/ml). The modified trichothecenes, FS-2 and FS-3, were not toxic even at 1 x 10(5) ng/ml. The baby hamster kidney cell bioassay proved to be a very sensitive and reproducible means of screening new trichothecene mycotoxins for relative cytotoxicity.

Animals↗
PubMed1991

Cocontamination of swine diets by aflatoxin and diacetoxyscirpenol.

The effects of dietary aflatoxin (AF) and diacetoxyscirpenol (DAS), singly and in combination, were evaluated in growing crossbred barrows. The experimental design consisted of 4 treatments of 9 barrows each fed diets containing 1) 0 mg AF and 0 mg DAS/kg feed (control), 2) 2.5 mg AF/kg feed, 3) 2.0 mg DAS/kg feed, or 4) 2.5 mg AF + 2.0 mg DAS/kg feed for 28 days (10-14 weeks of age). Production performance, serum biochemical, hematologic, and pathologic measurements were made. Body weight and body weight gain were significantly decreased by each toxin but more so by the combination treatment. The effects were additive in nature. Liver and spleen weights, as percentages of body weight, were increased by the AF and AF + DAS treatments, and AF or AF + DAS treatments induced diffuse hepatocellular vacuolar change, early portal fibrosis, and early bile duct hyperplasia. Aflatoxin increased serum values of creatinine and gamma glutamyl transferase, cholinesterase, and alkaline phosphatase activities; increased packed cell volume and hemoglobin; and decreased urea nitrogen and total iron binding capacity. DAS reduced serum iron binding capacity. The AF + DAS treatment increased serum gamma glutamyl transferase and alkaline phosphatase activities, increased hemoglobin, and decreased serum iron binding capacity. Generally, the combination treatment could be described as additive or less than additive, with most of the effects attributable to AF. Under the conditions and parameters monitored in this study, AF and DAS had no synergistic toxic effects when incorporated into diets of growing barrows.

Aflatoxins↗
PubMed1991

pH-dependent cytotoxicity of contaminants of phenol red for MCF-7 breast cancer cells.

The pH indicator phenol red (phenolsulfonphthalein) is present in most tissue culture media. Contaminants of this indicator have shown substantial estrogenic activity for estrogen-dependent cells in culture, including the human breast cancer-derived MCF-7 cell line. In the course of other studies, we observed that brief (1- to 4-h) incubations of these cells at 37 C in serum-free medium (Hanks' or Earle's Balanced Salts Solution) could be toxic to MCF-7 cells when the pH was increased above 7.4, but only if phenol red (10 micrograms/ml) was present in the medium. Because damaged/killed cells detached from the substratum (greater than 98% of detached cells stained with trypan blue), we used DNA assay of the cells remaining after treatment and wash (98% of the remaining cells were dye excluding) to further assess cytotoxicity. The MCF-7 cells were more susceptible to the cytotoxicity at lower cell densities, so further characterization of phenol red cytotoxicity was performed at cell densities of 1-10 micrograms DNA/2-cm2 well, or approximately 40,000-400,000 cells/ml medium. In the pH range of 7.0-8.2, 50% cell death was observed in the presence of phenol red at pH as low as 7.6-7.7, with nearly 100% of the cells killed by pH 8.0. Little effect was seen in phenol red-free medium at any part of the tested pH range or in medium that contained phenol red at pH less than or equal to 7.4. In time-course studies of cytotoxicity at pH 8.0 (phenol red, 10 micrograms/ml), greater than 50% cell damage could be observed after less than 1 h, and little cell recovery was observed if the pH was restored to 7.4. For phenol red samples from two major commercial sources, the concentration for half-maximal cytotoxicity (TD50) in dose-responses after 4 h at pH 8.0 showed TD50 values of 2 and 6 micrograms/ml, while the estrogenic activities, as half-maximal stimulation of estrogen-dependent proliferation, were identical at 2 micrograms/ml. Both the cytotoxic and estrogenic activities could be removed from the phenol red by extraction with diethyl ether. A number of contaminants of the commercial phenol red were detected by reverse phase C18 HPLC. Cytotoxicity and estrogen bioassays of each of the HPLC fractions indicated that the pH-dependent cytotoxicity was separate from the estrogenic activity and confirmed that neither activity was associated with the phenol red itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1990

A sensitive bioassay for detection of dietary estrogens in animal feeds.

Estrogen-responsive proliferation in the MCF-7 cell line was used as a bioassay for detection of dietary estrogens. The bioassay procedure was adapted to screen for estrogenic activity in feedstuffs that have been associated with hyperestrogenism in livestock. Methanolic feed extracts were added to the cell culture medium at microliter/ml concentrations for 4 days, after which the cell proliferation response was measured as DNA content. The half-maximal response for estradiol occurred at 2 pM, or 0.54 pg/ml. For zearalenone, a weaker estrogen, the half-maximal response occurred at approximately 200 pM, or 64 pg/ml. The bioassay was calibrated against a number of known estrogens (estradiol, diethylstilbestrol, zearalenone, zearalanol [cattle implant], beta-zearalenol, zearalane), including the naturally occurring phytoestrogens (formononetin, genistein, daidzein, biochanin A, and coumestrol). The estrogenic activity of feed samples was expressed as equivalents of zearalenone (ppm zearalenone) that would have to be present to equally stimulate proliferation of the MCF-7 cells. The sensitivity of the bioassay was 0.05-0.1 ppm equivalents of zearalenone in feed, well below the threshold level associated with reproductive problems. The feed additive melengestrol acetate (MGA) showed no estrogenic activity in this assay. Estrogenic activity of feed extracts was confirmed by competitive inhibition with the antiestrogens tamoxifen or LY156758 (keoxifene) to show that stimulation of growth by feed extracts was through an estrogenic mechanism. Confirmation of known estrogens was by tandem mass spectroscopy. The assay is a sensitive and reliable screening procedure for detecting estrogenic activity in feedstuffs.

Animal Feed↗
PubMed1990

Efficacy of a hydrated sodium calcium aluminosilicate to reduce the toxicity of aflatoxin and T-2 toxin.

A hydrated sodium calcium aluminosilicate (HSCAS) was incorporated into diets (.5%) containing 3.5 mg of aflatoxin (AF) per kg and 8.0 mg of T-2 toxin (T-2) per kg, singly, and in combination. Male broiler chicks (n = 480) were provided with feed and water for ad libitum consumption from 1 to 21 days of age. Body weight gains were significantly depressed by AF and T-2, singly, and further decreased by the combination of the two toxins. Efficiency of feed utilization was not affected. The AF alone and the AF plus T-2 combination caused increases in relative liver, kidney, proventriculus, gizzard, spleen, and pancreas weights. Treatment-related changes in hematological and serum biochemical values and enzyme activities were observed. Oral lesions were observed only in chicks receiving the T-2 diets. The HSCAS fed singly did not alter any of the parameters measured but it did diminish the toxicity of AF for many parameters but did not appear to alter the toxicity of T-2. Addition of HSCAS to the AF plus T-2 combination diet diminished some of the effects of the toxin combination. These findings indicate that HSCAS can diminish many of the adverse effects of dietary AF in the chicken, but it has no effect on T-2 toxicity.

Aflatoxins↗
PubMed1990

Effects of treatment of growing swine with aflatoxin and T-2 toxin.

Effects of dietary aflatoxin (AF) and T-2 toxin, singly and in combination, were evaluated in growing crossbred (Yorkshire x Landrace x Hampshire) pigs. The experimental design consisted of 4 treatment groups of 6 barrows each fed diets containing 0 mg of AF and T-2/kg of feed (controls; group 1), 2.5 mg of AF/kg of feed (group 2), 10 mg of T-2/kg of feed (group 3), or 2.5 mg of AF plus 10 mg of T-2/kg of feed (AF + T-2; group 4) ad libitum for 28 days (7 to 11 weeks of age). Production performance, and serum biochemical, and hematologic evaluations were made weekly. Body weight and body weight gain were depressed by all toxin treatments, but the effect of AF and T-2 toxin in combination was less than additive. Liver and kidney weights, as a percentage of body weight, were increased by AF treatment, and heart weight, as a percentage of body weight, was increased by T-2 treatment. Treatment with T-2 toxin induced necrotizing contact dermatitis on the snout, buccal commissures, and prepuce. Consumption of AF resulted in increased serum activities of alkaline phosphatase, aspartate transaminase, cholinesterase, and gamma-glutamyltransferase, and decreased serum concentrations of urea nitrogen, cholesterol, albumin, total protein, calcium, potassium, magnesium, and phosphorus. Consumption of T-2 toxin resulted in increased serum triglyceride concentration and decreased serum iron concentration. Treatment with AF induced lower serum unsaturated iron-binding capacity and high RBC count, PCV, hemoglobin concentration, WBC count, and prothrombin time.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMed1989

Organochlorine insecticide problems in livestock.

1. Antidotal therapy for acute OC intoxications is symptomatic and supportive. Use sedatives to control convulsions and AC to adsorb any pesticide remaining in the gut, and wash topical exposures. 2. Published kinetics should be applied to field situations with caution. In general, residues decline relatively quickly immediately following the last exposure; thereafter, the rate slows considerably. The elimination-rate constant and, hence, the half-life of any given OC is dependent on many variables that usually are not known under field conditions. This fact may result in serious errors if literature values are relied on too heavily in predicting the outcome of "natural" contamination. As a rule of thumb, elimination data derived from animals experimentally fed to plateau concentrations may be regarded as fairly conservative for such purposes, if the contaminated animals are maintained in a normal fashion. Probably the least risky method of predicting return to marketability is using frequent samples, taken at regular intervals (for example, 1 to 2 weeks) during the first month after last exposure, to adjust literature values. 3. Residues from larger dosages and shorter exposures tend to be smaller in proportion to dose and are eliminated more quickly than those resulting from longer exposures and smaller doses. 4. Activated charcoal is of universal benefit only if given immediately after exposure. 5. Pharmaceutical modifiers of xenobiotic metabolism such as phenobarbital are of very limited value. The particular type and amount of residual OC and the potential economic benefit of therapy should be considered thoroughly before undertaking such therapy. In most cases, the expense won't be justified. 6. Mineral oil increases the fecal excretion of some OC. Fecal excretion, however, is so small in relation to total body burdens that even a several-fold increase may not be useful economically except when residue concentrations are low to start with. 7. Nutritional strategies have the advantage of being very cheap. Practitioners should remember, however, that tissue concentrations actually may increase as body fat decreases. The costs of maintaining animals for an extra 6 to 10 months should be considered before undertaking such an effort.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Individual and combined toxicity of deoxynivalenol and T-2 toxin in broiler chicks.

Effects of feeding diets containing deoxynivalenol (DON)-contaminated wheat (16 mg DON/kg) and purified T-2 toxin at 4 mg/kg singly and in combination were characterized in male broiler chicks from 1 day to 3 wk of age. Total body weight gains and final body weights were significantly reduced by the DON/T-2 toxin combination but were not significantly affected by the toxins singly. The efficiency of feed utilization was reduced in chicks fed either of the diets containing DON-contaminated wheat. The incidence and severity of oral lesions induced by T-2 toxin was increased in the DON/T-2 toxin combination. Several parameters not altered by DON or T-2 toxin singly were significantly affected by the combination, indicating that the combination may pose a potentially greater problem to the poultry industry than either of the mycotoxins individually.

Animal Feed↗
PubMed1989

Influence of ochratoxin A and T-2 toxin singly and in combination on broiler chickens.

Effects of feeding diets containing ochratoxin A (OA) at 2.0 mg/kg and T-2 toxin at 4.0 mg/kg singly and in combination were characterized in male broiler chicks from 1 day to 3 wk of age. Body weights were depressed by feeding OA singly, T-2 singly, and the OA/T-2 combination. The efficiency of feed utilization was reduced in the OA and OA/T-2 combination-fed groups. The T-2 toxin caused oral lesions, anemia, and changes in some serum biochemical values. Feeding OA resulted in increases in relative liver, kidney, gizzard, and pancreas weights, a microcytic hypochromic anemia, and changed serum chemistries. The OA/T-2 combination caused increases in relative liver, kidney, proventriculus, and gizzard weights and variable serum biochemistries. The effects of OA and T-2 were additive for reduced body weight gains, mean corpuscular volume, and for reduced serum levels of total protein, and for reduced lactate dehydrogenase activity. A significant interaction occurred between OA and T-2 causing elevated serum triglyceride levels and decreased gamma glutamyl transferase activity and calcium levels. Degenerative renal tubular changes were observed in some OA and OA/T-2 combination-fed chicks. These data indicate that OA and T-2 in combination may be more toxic for some parameters than the individual mycotoxins, and may pose a greater problem for the poultry industry than either of the mycotoxins individually.

Animal Feed↗
PubMed1988

Toxic synergism between aflatoxin and T-2 toxin in broiler chickens.

The individual and combined effects of aflatoxin and T-2 toxin were studied in male broiler chicks (Hubbard X Hubbard). The experimental design was a 2 X 2 factorial design with dietary treatments of 0 and 2.5 micrograms/g aflatoxin and 0 and 4.0 micrograms/g T-2 toxin. The broilers were obtained at 1 day of age and housed in electrically heated batteries with feed and water available ad libitum until they reached 3 wk of age. Aflatoxicosis in this study was characterized by a significant (P less than .05) reduction in body weight, changes in red blood cell counts and serum levels of protein, albumin, glucose, cholesterol, and calcium, and magnesium, activity of the serum enzymes lactic dehydrogenase and alkaline phosphatase, and a significant (P less than .05) increase in relative weights of the liver, kidney, spleen, pancreas, proventriculus, and heart. Dietary T-2 toxin alone caused oral lesions, a significant (P less than .05) decrease in serum protein, albumin, potassium, and magnesium levels, and a significant (P less than .05) decrease in the activity of the serum enzymes lactic dehydrogenase and alkaline phosphatase. In the combination treatment of aflatoxin and T-2 toxin, significant (P less than .05) interactive effects were seen through a decrease in body weights, increase in the relative weights of the kidney, gizzard, and heart, and decrease in mean corpuscular volume and serum levels of potassium. These data indicate that aflatoxin and T-2 toxin can interact to produce synergistic toxicity. This synergism is a threat to poultry production due to the prevalence of these mycotoxins and severity of the interactive toxicity of these mycotoxins.

Aflatoxins↗
PubMed1987

The effects of zearalenone on reproduction in swine. I. The relationship between ingested zearalenone dose and anestrus in non-pregnant, sexually mature gilts.

Ninety-nine sexually mature, non-pregnant gilts were checked for estrus daily with a mature boar and then allocated at estrus (D O) to receive 2 kg/d of a diet containing 0, 1, 5 or 10 ppm purified zearalenone between D 5 and 20 of the estrous cycle during two seasons of the year (winter and summer). None of the gilts exhibited any visual signs of "hyperestrogenism" and there was no effect of season on interestrous interval (P>0.05). A significant effect of zearalenone dose on inter-estrous interval was detected (P<0.001). Gilts receiving 0 or 1 ppm had similar inter-estrous intervals (21.0+/-0.3 and 21.5+/-0.8 d, respectively) whereas gilts receiving 5 and 10 ppm had extended cycles (29.2+/-2.9 and 32.7+/-3.3 d, respectively). Plasma progesterone concentrations at D 19 to 21 were higher in gilts with extended cycles (P<0.001) and corpora lutea (CL) were present at laparotomy. Some 86% of these retained CL underwent spontaneous regression resulting in the onset of estrus within the next 30 d. Fecal zearalenone concentrations rose during ingestion of contaminated diets and declined to pretreatment values within 2 d (1 ppm) to 8 d (10 ppm) of the cessation of treatment. These data show that feeding zearalenone at concentrations of 5 to 10 ppm from D 5 to 20 of the estrous cycle causes luteal maintenance and extended inter-estrous intervals. Spontaneous regression of these CL usually occurs within 30 d after zearalenone is removed from the diet. Fecal zearalenone analysis does not appear to be an effective method for determining prior exposure to zearalenone when carried out more than a few days following the last ingestion of zearalenone.

Journal Article↗
PubMed1984

Plasma pentachlorophenol concentrations in calves exposed to treated wood in the environment.

Six calves were fed grain and hay from a pentachlorophenol (PCP)-treated feeder twice daily. Samples of blood were collected twice a week. Plasma PCP concentrations increased rapidly to a maximum of 1,086 microgram/L within 10 days. After the 3rd week, calves were denied access to the treated feeder; PCP values returned rapidly to near base line (before calves were fed from the treated feeder). After base-line plasma PCP values were reached, 4 of the 6 calves were housed in a total confinement building and exposed (by inhalation) to lumber that was commercially treated with PCP. The building itself was free of structural PCP-treated lumber. The ratio of building volume to treated wood surface was approximately 49 to 1. During the 3 weeks the calves were confined, PCP values did not increase and were markedly lower than those associated with oral exposure to treated wood. Oral dosing of calves with PCP in capsules--0.05 and 0.5 mg/kg--resulted in maximal plasma PCP values of 1,449 and 9,555 micrograms/L, respectively. Oral exposures (feeding from contaminated feeder; capsule) appeared to be more important than inhalation in causing increased plasma PCP concentrations in cattle. Exposure from these sources may be estimated by comparison with experimental values from dose-response studies. Feeding from treated feeders resulted in lower plasma PCP values than did dosing with 0.05 mg/kg daily.

Administration, Oral↗
PubMed1981

Relationship of sulfamethazine in swine diets and resultant tissue concentrations, using Tishler and gas liquid chromatographic methods.

Sulfamethazine (110 mg/kg of feed) was fed to 4 groups of pigs for 10 days. Each group was then fed withdrawal rations containing 0, 1.1, 11.0, or 110.0 mg/kg of feed for 10 days before slaughter. A 5th group was fed a sulfamethazine-free diet only. Fat, kidney, liver, and muscle from each pig were analyzed by several laboratories, using the Tishler Bratton-Marshall (BM) and gas liquid chromatographic (GLC) methods. Mean background (BG) amounts of sulfamethazine, as measured in control tissues, were essentially negligible using GLC; however, BM BG values (mean +/- SD), expressed as milligrams of sulfamethazine per kilogram of edible animal tissue (ppm) were: fat 0.019 +/- 0.003, kidney 0.048 +/- 0.012, liver 0.053 +/- 0.034, and muscle 0.018 +/- 0.017. Regression of tissue sulfamethazine on feed sulfamethazine, as measured by GLC and BM adjusted for BM-BG values, yielded essentially linear plots. Values obtained by GLC and corrected BM were highly correlated, but the variability was higher, using GLC. The linear model predicted that the dietary sulfamethazine required to produce 0.1 ppm in liver as measured by the BM, BM-BG, and GLC were 1.6, 2.8, and 3.4 ppm, respectively. The concentrations necessary to produce 0.1 ppm in muscle were 5.3, 6.2, and 5.5 ppm. The thin-layer chromatographic method of screening swine plasma was a good predictor of tissue sulfamethazine values.

Animal Feed↗
PubMedDate not supplied

Developmental toxicity of purified fumonisin B1 in pregnant Syrian hamsters.

The purpose of this study was to characterize the developmental toxicity of fumonisin B1 (FB1), a mycotoxin produced by Fusarium moniliforme, on fetal Syrian hamsters. Fusarium moniliforme has been associated with a variety of diseases in animals and esophageal cancer in humans. Purified FB1 causes leukoencephalomalacia in horses and is hepatocarcinogenic in rats. Fumonisin B1 has been associated with fetal toxicity in rats and mice and has been suggested to be involved in reproductive failure in pregnant sows. Results from a preliminary developmental toxicity study using an aqueous extract of F. moniliforme corn-culture material in hamsters suggested that FB1 was a developmental toxicant. These results were verified using purified FB1. Six groups of ten time-mated female Syrian hamsters were dosed with 0.0-18 mg kg(-1) day(-1) of FB1 by gavage on days 8-12 of gestation and euthanized on day 15. Live fetuses were weighed and examined for gross external and internal abnormalities and skeletal anomalies. Purified fumonisin B1 was shown to cause dose-dependent fetal death and delayed fetal development without causing fetal abnormalities.

Abnormalities, Drug-Induced↗