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Biomedical subjects

T D Phillips

Publications and source records attributed to T D Phillips.

At least 91 records · Page 5Linked to original sources

Effects of feeding mature White Leghorn hens diets that contain deoxynivalenol (vomitoxin).

Mature White Leghorn hens that had been fed a commercial laying diet were changed to a wheat-based diet over a period of 42 days. Two groups were formed based on equivalent egg production and body weights and randomly assigned to either a control (noncontaminated) wheat diet or a naturally contaminated deoxynivalenol (DON, vomitoxin) wheat diet (18 mg DON/kg). Hens were provided their respective diets and water ad libitum for 112 days along with 16 hr of light. The DON-contaminated diet did not significantly influence hen body weights, hen day egg production, egg weights, or efficiency of feed utilization. Internal egg quality, as measured by albumin height, was slightly, although significantly, improved by feeding the DON-contaminated wheat diet. Egg shell weight and percent egg shell were slightly, although significantly, decreased by feeding the DON-contaminated diet, whereas shell thickness was not altered. No deleterious effects were observed in fertility, hatchability, or chick weights at hatch. The results indicate that laying hens are affected only slightly when fed naturally contaminated wheat diets containing approximately 18 mg DON/kg for 112 days.

Animals↗

Determination of deoxynivalenol (vomitoxin) by high-performance liquid chromatography with electrochemical detection.

A rapid method for the analysis of deoxynivalenol (DON) was developed using high-performance liquid chromatography (HPLC) with reductive electrochemical detection (ED). Deoxynivalenol produced by Fusarium roseum growing on solid cornmeal and rice substrates and from naturally contaminated wheat was extracted and quantitated via ED. DON levels in wheat were verified by gas chromatography and structurally confirmed by mass spectrometry. DON was optimally resolved by HPLC employing a radially compressed octadecylsilane column and a mobile phase of deoxygenated methanol-40 mM borate buffer (35:65) at a flow-rate of 1.0 ml/min. Under these conditions DON exhibited an average retention time of 3.6 min. Reductive ED (-1.4 V) allowed a 12-fold increase in sensitivity and greater selectivity than classical UV absorption at 224 nm. A detection limit for DON of 25 pg/microliter was achieved under these conditions. The determination of DON in crude grain extracts was hindered by extractable interfering substances, whereas ED was more functional-group selective (i.e. reduction of the carbonyl moiety). ED permits a direct quantitation of DON from crude grain extracts and may facilitate the determination of this agent and associated metabolites in biological samples.

Chromatography, High Pressure Liquid↗

Individual and combined effects of aflatoxin and deoxynivalenol (DON, vomitoxin) in broiler chickens.

The individual and combined effects of aflatoxin and deoxynivalenol (DON) were evaluated in young broiler chickens (Hubbard X Hubbard). The experimental design was a 2 X 2 factorial with treatments of 0 and 2.5 micrograms of aflatoxin/g of feed (ppm) and 0 and 16 micrograms of DON/g of feed. The broilers were maintained on these dietary treatments from hatching to 3 weeks of age in electrically heated batteries with feed and water available ad libitum. The aflatoxin treatment significantly (P less than .05) decreased body weight; weight gain; increased the relative weight of the spleen, liver, and kidney; induced hepatic hyperlipemia; decreased activity of lactic dehydrogenase; and decreased serum levels of protein, albumin, and phosphorus. The toxicity of DON was expressed through reduced growth rate, increased feed conversion; increased relative weight of the gizzard, anemia, decreased activity of lactic dehydrogenase, and decreased serum triglycerides. The interaction between aflatoxin and DON was characterized by reduced growth rates; increased feed conversion, increased relative weight of the proventriculus, gizzard, spleen, liver, and kidney, anemia, hepatic hyperlipemia, decreased activity of alkaline phosphatase, glutamic oxalacetic transaminase, and lactic dehydrogenase, and decreased serum levels of protein, albumin, uric acid, cholesterol, triglycerides, and calcium. These data demonstrate that both aflatoxin and DON can limit broiler performance and adversely effect broiler health. The effects of the combination of aflatoxin and DON on broiler performance and health was more severe than the individual effects of these mycotoxins; however, the interaction was not severe enough to represent toxic synergy and can best be characterized as additive toxicity.

Aflatoxins↗

Influence of ochratoxin A and vanadium on various parameters in growing chicks.

The effects of ochratoxin A (OA) and vanadium (V) singly and in combinations, at levels that could be encountered under field conditions, were determined in male Leghorn chicks. The chicks were fed a control diet containing the following additives: none; 12.5 mg V/kg; 25.0 mg V/kg; 2.5 mg OA/kg; 2.5 mg OA plus 12.5 mg V/kg; and 2.5 mg OA plus 25.0 mg V/kg. These data show that V, singly at levels of 12.5 or 25.0 mg/kg of diet, did not adversely affect body weight gain at 1, 2, 3, or 4 weeks of age. Body weight gains of the chicks receiving the diets containing OA singly were significantly lower than the controls except during the 1- to 7-day period. Body weight gains of chicks receiving the OA in combination with either level of V were significantly lower than any of the other groups during the 1- to 7- and 22- to 28-day periods. The quantity of feed required per unit of gain was increased slightly by the addition of OA at 2.5 mg/kg and the addition of V at 12.5 or 25.0 mg/kg and, to a greater extent, by the OA-V combinations. The relative liver and kidney weights were higher in the groups receiving OA singly or in combination with V. When compared to the controls, relative gizzard weights were significantly higher in the two combination groups; whereas the relative proventriculus weights were significantly higher only in the group receiving the 2.5 mg OA plus 25.0 mg V/kg combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of deoxynivalenol in a wheat ration fed to growing lambs.

A wheat diet containing deoxynivalenol (vomitoxin) at 15.6 mg/kg was fed to crossbred lambs for 28 days. Feed consumption, weight gain, and feed efficiency of deoxynivalenol-treated lambs did not differ (P less than 0.05) from those values of controls. Group differences were not noted for hematologic or serum biochemical variables, and gross or microscopic lesions were not observed in treated lambs.

Animal Feed↗

Renal tubular secretion and reabsorption as factors in ochratoxicosis: effects of probenecid on nephrotoxicity.

Ochratoxin A (OA) is a food-borne fungal metabolite capable of producing nephrotoxicity. Renal clearance of [3H]OA and the effects of probenecid on clearance were compared in sham-operated and partially nephrectomized (surgical removal of 70% of the total renal mass), impaired renal function rats. Sham-operated and partially nephrectomized rats cleared OA at 0.109 and 0.078 ml/min, respectively. These values were significantly lower than glomerular filtration rate (GFR) determined by inulin clearance, indicating net tubular reabsorption. Clearance of a single dose of OA in both sham-operated and partially nephrectomized rats pretreated with probenecid was significantly diminished and provided evidence for the involvement of secretory processes in the elimination of OA. Probenecid (administered before OA or simultaneously with OA) failed to prevent nephrotoxicity in rats exposed to five daily doses of mycotoxin. On the contrary, enhanced nephrotoxicity was exhibited. Decreases in urine osmolality, Na+ and K+ concentrations, and body weight were prominent and, interestingly, renal levels of parent OA were increased (over OA treatment alone) in the presence of probenecid. These data suggest that renal tubular secretion and reabsorption are important factors in modulating the nephrotoxicity of OA and may facilitate the residual persistence of this mycotoxin in the kidneys (via renal recycling). Renal metabolism may contribute to the detoxification of OA.

Absorption↗

Metabolism of aflatoxin B1 by rat hepatic microsomes induced by polyhalogenated biphenyl congeners.

The metabolism of aflatoxin B1 to aflatoxins M1 and Q1 by rat liver microsomes from animals pretreated with polychlorinated or polybrominated biphenyl congeners depended on the structure of the halogenated biphenyl inducers. Microsomes from rats treated with phenobarbital (PB) or halogenated biphenyls that exhibit PB-type activity preferentially enhanced the conversion of aflatoxin B1 to aflatoxin Q1. In contrast, microsomes from rats treated with 3-methylcholanthrene (MC) or halogenated biphenyls that exhibit MC-type induction activity increased the metabolism of aflatoxin B1 to aflatoxin M1. The coadministration of PB and MC produced microsomes that exhibited both types of induction activity (mixed type) in catalyzing the oxidative metabolism of diverse xenobiotic agents. However, PB-plus-MC-induced hepatic microsomes from immature male Wistar rats preferentially increased the metabolism of aflatoxin B1 to aflatoxin M1 but did not enhance the conversion of aflatoxin B1 to aflatoxin Q1. Comparable results were observed with microsomes from rats pretreated with halogenated biphenyls classified as mixed-type inducers; moreover, in some cases there was a significant decrease in the conversion of aflatoxin B1 to aflatoxin Q1 (compared with that of controls treated with corn oil).

Aflatoxins↗

Toxicity of ochratoxin A and vanadium to growing chicks.

The effects of ochratoxin A (OA) and vanadium (V), singly and in combination, were determined in male Leghorn chicks from 1 to 28 days of age. The chicks were fed a control diet containing the following additives: A) none; B) 2.5 mg OA/kg; C) 50 mg V/kg; D) 2.5 mg OA plus 50 mg V/kg. These data show that body weight gains were significantly reduced by OA and V singly, and a toxicity-enhancing synergism exists between OA and V, which caused a further reduction in performance. The OA-V combination caused a significant increase in the relative weights of the liver, kidney, gizzard, and proventriculus and a significant decrease in the relative weights of the bursa of Fabricius. This decrease in bursal weight was due to atrophy of lymphoid follicles as indicated by the increase in the histologic lesion score. Uric acid in serum was increased, and albumin, calcium, and phosphorus were decreased in the OA-V combination group. There were also small but significant changes in the hematological parameters measured. Distribution of OA to the liver and kidney was not altered, nor was the distribution of V to the liver, kidney, or muscle tissue. Histologic lesions in kidneys were mild but were more prevalent in chicks in the OA-V combination group.

Animal Feed↗

Teratogenic effects of Ochratoxin A in rats with impaired renal function.

The teratogenic potential of Ochratoxin A (OA), was compared in impaired renal function (IRF) and sham-operated (SO) female rats. Surgical removal of approximately 70% of the total renal tissue was accomplished utilizing unilateral ligation/electrocoagulation procedures. Control animals were sham-operated. All animals were allowed a period of 27 days to recover post surgery. IRF rats exhibited normal mating tendencies and the pregnancy rate was 100%. A single, subcutaneous teratogenic dose of OA (1.75 mg/kg) on gestation day 7 resulted in significantly increased fetal resorptions, decreased fetal body weights and increased fetal malformations in both IRF and SO animals, although the incidence of gross malformations was greater in IRF rats. A subthreshold teratogenic dose (i.e. 1 mg/kg) did not produce any significant increase in embryotoxicity or fetal malformations in IRF animals compared to SO rats.

Abnormalities, Drug-Induced↗

Effect of simultaneous prenatal exposure to ochratoxin A and citrinin in the rat.

Ochratoxin A (OA) and citrinin (CT) are food-borne mycotoxins produced by several fungal species of the genera Aspergillus and Penicillium. Both are teratogenic in the rat. To determine the prenatal effects of simultaneous exposure to these toxins, pregnant Sprague-Dawley rats were injected either with a single individual subthreshold teratogenic dose of OA (1 mg/kg) or CT (30 mg/kg) or with both toxins. Toxins were dissolved in 5% sodium bicarbonate and administered subcutaneously on one of gestation d 5, 6, 7, 8, 10, 11, or 14. Maternal body weight gain of animals in the combination group was similar to other treatment groups and the control. Approximately 22-40% mortality in dams occurred on gestation d 5, 6, 7, and 14. Other than d 7, there was no significant effect on the number of implants. Treatment on d 5 or 7 resulted in increased fetal resorptions. Fetal body weights were not decreased significantly. OA and CT in combination resulted in a significant increase in gross malformations on d 6 and 7, visceral anomalies on d 5, 7, 8, and 10, and skeletal defects on d 5, 6, 7, 8, 10, and 14. When administered individually, OA and CT resulted in very few fetal resorptions. Fetal body weights were not significantly different except on d 8 of gestation following CT treatment. Individual toxin treatment resulted in minimal malformations on all gestation days. These results suggest that OA and CT, when administered concurrently, may interact to enhance prenatal toxicity and teratogenicity, and these results have focussed attention on the public health hazards of contamination of food with these mycotoxins.

Abnormalities, Drug-Induced↗

Effects of ochratoxin A in the partially nephrectomized rat.

The effects of ochratoxin A (OA), a nephrotoxic mycotoxin, were investigated in partially nephrectomized (PN) rats (approximately 70% reduction in renal mass) following compensatory hypertrophy of the renal remnant. Renal function stabilized 27 d after surgery. PN rats compensated for the initial loss of renal function except for glomerular filtration rate (GFR, inulin clearance); this remained significantly impaired. Sham-operated (SO) rats cleared inulin and p-aminohippurate (PAH) at rates of 3.84 and 7.49 ml/min, respectively, while compensated PN rats cleared inulin at 2.51 and PAH at 8.84 ml/min. Daily administration of low levels of OA produced decreased urine osmolality and body weight with a modest increase in urinary protein of PN versus SO rats. OA-treated rats cleared inulin, creatinine, and PAH at rates significantly lower than nontreated controls: 0.89 and 1.96 ml/min for inulin, 0.35 and 0.56 ml/min for creatinine, and 2.29 and 6.23 ml/min for PAH. Histopathological findings indicated a considerable increase in renal tubular necrosis and subcellular damage (i.e., loss of cytoplasmic ground substance, vacuolization, degeneration of mitochondria, and reorganization of endoplasmic reticulum) in PN animals versus controls, concurrent with alteration in renal function. These results verify that the nephrotoxic action of OA is elicited mainly in renal proximal tubules and is enhanced in the PN rat.

Animals↗

Ochratoxin A-induced teratogenesis in rats: partial protection by phenylalanine.

Ochratoxin A (OA), an important foodborne mycotoxin, is a potent teratogenic and nephrotoxic agent produced by several species of Aspergillus and Penicillium. OA is a known inhibitor of protein synthesis via competition with phenylalanine (Phe) in the phenylalanyl-tRNA synthetase-catalyzed reaction. It also has been reported that a variety of toxic effects of OA can be prevented by Phe. This study was designed to determine whether Phe could prevent or diminish the teratogenic effects of OA in rats. Pregnant Sprague-Dawley rats were injected with a single individual dose of OA (1.75 mg/kg) alone or in combination with a single dose of Phe (20 mg/kg) or in combination with either a single or daily dose of Phe (25 mg/kg). OA dissolved in 5% sodium bicarbonate and Phe dissolved in normal saline were administered subcutaneously on gestation day 7 to rats. The incidences of OA-induced fetal malformations (gross and skeletal) were significantly diminished in the presence of added Phe. These results indicate that coadministered Phe provides partial prenatal protection from the teratogenic effects of OA.

Abnormalities, Drug-Induced↗

Aflatoxin B1 metabolism in the rat: polyhalogenated biphenyl enhanced conversion to aflatoxin M1.

The effects of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) on the formation in vitro of aflatoxin Q1 and aflatoxin M1 from aflatoxin B1 by rat-liver microsomes were investigated. AFB1 metabolism by hepatic microsomes from PBB- and PCB-treated rats resulted in 16- and 30-fold increases, respectively, in levels of aflatoxin M1. The enhanced formation of aflatoxin M1 did not correlate with PBB and PCB stimulation of benzo[a]pyrene hydroxylase (AHH) activity. Studies in vivo clearly demonstrated enhanced secretion of aflatoxin M1 by female lactating rats with prior exposure to PCBs. PCB pretreatment enhanced the activity of mammary as well as hepatic tissue microsomal preparations in converting aflatoxin B1 to aflatoxin M1. Our findings indicate that PCB exposure increases the production of aflatoxin M1 in vitro and also increases the levels of aflatoxin M1 released into the milk.

Aflatoxin B1↗

A chick model for impaired renal function.

To evaluate some of the metabolic consequences of impaired renal function (IRF) in the chick, a surgical method to induce IRF was developed that involves the destruction of approximately 85% of the renal mass by ureteral ligation. It is relatively simple with minimal time and labor required, produces low mortality, requires little specialized postoperative care, and is readily reproducible. Three-week-old control, sham-operated, and IRF chicks were bled by cardiac puncture and biochemical measurements were made on serum samples. Serum uric acid concentration was the most sensitive indicator of IRF, with mean levels in the IRF chicks being increased above control and sham-operated chicks 3.3-, 2.7-, 2.0-, and 1.2-fold at 1, 3, 7, and 14 days, respectively. The gradual decline in uric acid levels is most likely related to the functional recovery and hypertrophy of the remaining renal mass. The IRF chick model will be useful to provide information on renal aspects of the toxicity, distribution, metabolism, and elimination of nephrotoxic agents.

Animals↗

Toxicity of vanadium in female Leghorn chickens.

A study was conducted to determine the influence of dietary vanadium, fed after the onset of production, on hen day egg production, body weight changes, and mortality in laying breed chickens. Calcium orthovanadate was fed to 29-week-old female laying breed chickens at calculated levels of 0, 12.5, 25, 50, and 100 ppm dietary vanadium for five consecutive 28-day laying periods. Hen-day egg production and hen body weights were not influenced by the addition of 12.5 or 25 ppm dietary vanadium. Overall hen body weights and the hen day egg production were decreased in hens fed diets to which 50 ppm vanadium was added with a severe reduction in both parameters at 100 ppm. There were no mortalities during the experiment in the groups fed the 0, 12.5, 25, or 50 ppm vanadium diets. Mortality in the group fed the 100 ppm vanadium diet was 11, 39, and 56% at the end of the 28-day Periods 3, 4, and 5, respectively. There were no significant differences in egg weights, although a trend existed for lower egg weights with increasing levels of dietary vanadium.

Animals↗