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S W Kennedy

Publications and source records attributed to S W Kennedy.

At least 19 recordsLinked to original sources
PubMed1999

Relationships between environmental organochlorine contaminant residues, plasma corticosterone concentrations, and intermediary metabolic enzyme activities in Great Lakes herring gull embryos.

Experiments were conducted to survey and detect differences in plasma corticosterone concentrations and intermediary metabolic enzyme activities in herring gull (Larus argentatus) embryos environmentally exposed to organochlorine contaminants in ovo. Unincubated fertile herring gull eggs were collected from an Atlantic coast control site and various Great Lakes sites in 1997 and artificially incubated in the laboratory. Liver and/or kidney tissues from approximately half of the late-stage embryos were analyzed for the activities of various intermediary metabolic enzymes known to be regulated, at least in part, by corticosteroids. Basal plasma corticosterone concentrations were determined for the remaining embryos. Yolk sacs were collected from each embryo and a subset was analyzed for organochlorine contaminants. Regression analysis of individual yolk sac organochlorine residue concentrations, or 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs), with individual basal plasma corticosterone concentrations indicated statistically significant inverse relationships for polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs), total polychlorinated biphenyls (PCBs), non-ortho PCBs, and TEQs. Similarly, inverse relationships were observed for the activities of two intermediary metabolic enzymes (phosphoenolpyruvate carboxykinase and malic enzyme) when regressed against PCDDs/PCDFs. Overall, these data suggest that current levels of organochlorine contamination may be affecting the hypothalamo-pituitary-adrenal axis and associated intermediary metabolic pathways in environmentally exposed herring gull embryos in the Great Lakes.

Adrenal Cortex Diseases↗
PubMed1998

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Animals↗
PubMed1997

Subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl in rats.

The subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl (PCB 128) was investigated in rats following dietary exposure at 0, 0.05, 0.5, 5, or 50 ppm for 13 wk. The growth rate was not affected by treatment and no apparent clinical signs of toxicity were observed. There was a significant increase in liver weight in the 50 ppm females. The liver ethoxyresorufin deethylase (EROD) activity was increased by five- and fourfold in the highest dose males and females, respectively, while aminopyrine demethylase (ADPM) activity was significantly increased only in the highest dose females. Liver vitamin A was significantly reduced in the highest dose females. No other biochemical or hematological effects were observed. Treatment-related histopathological changes were seen in the thyroid and liver, and to a lesser extent in the bone marrow and thymus. Residue data showed a dose-dependent accumulation of PCB 128 in the following tissues: fat, liver, kidney, brain, spleen, and serum, with the highest concentration being found in fat followed by liver and kidney. Based on these data, the no-observable-adverse-effect level of PCB 128 was judged to be 0.5 ppm in diet or 42 micrograms/kg body weight.

Adipose Tissue↗
PubMed1997

Halogenated aromatic hydrocarbon-mediated porphyrin accumulation and induction of cytochrome P4501A in chicken embryo hepatocytes.

Concentration-dependent induction of cytochrome P4501A (CYP1A) and intracellular porphyrin accumulation were observed following treatment of chicken embryo hepatocyte (CEH) cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4'-tetrachlorobiphenyl (PCB 77, IUPAC nomenclature), 2,3',4,4',5-pentachlorobiphenyl (PCB 118), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169), and a commercial mixture of PCBs (Aroclor 1254). For these halogenated aromatic hydrocarbons (HAHs), or mixture, maximal CYP1A activity [measured as ethoxyresorufin-O-deethylase (EROD) activity] and immunodetectable protein were observed at concentrations just prior to, or coincident with, the concentrations at which porphyrin accumulation became evident. Both immunodetectable CYP1A protein and catalytic activity decreased at high concentrations of these compounds, but the rate and extent of decrease of immunodetectable CYP1A protein varied. Time-course studies with PCB 77 indicated a decrease in potency and an increase in maximal CYP1A induction between 24 and 48 hr of exposure which may indicate in vitro metabolism of this HAH. Intracellular accumulation of total porphyrins without CYP1A induction, was observed for 2,2',5,5'-tetrachlorobiphenyl (PCB 52), 2,2',6,6'-tetrachlorobiphenyl (PCB 54), 2,2',3,5',6-pentachlorobiphenyl (PCB 95), 2,2',4,5,5'-pentachlorobiphenyl (PCB 101), 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136), and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153). Overall, these results are consistent with a role for CYP1A induction and/or Ah receptor activation in porphyrin accumulation mediated by HAHs with a planar configuration, whereas those that are not planar may mediate porphyrin accumulation by a mechanism not involving induction of CYP1A.

Animals↗
PubMed1997

Ethoxyresorufin-O-deethylase (EROD) inducing potencies of planar chlorinated aromatic hydrocarbons in primary cultures of hepatocytes from different developmental stages of the chicken.

In vitro induction of ethoxyresorufin O-deethylase (EROD) activity in cell cultures is an extensively validated tool for measuring overall potencies of mixtures of halogenated aromatic hydrocarbons (HAHs) in samples from the abiotic or biotic environment. For risk assessment with special attention to effects in wild birds, an assay was developed that makes use of chicken embryo hepatocytes. However, it was questioned whether compound-specific responses are consistent at the various developmental stages. The results of our present study show that there are considerable differences between early and late embryonal and post-hatching stages. The induction of EROD was measured in primary chicken hepatocyte cultures. The cells were isolated at day 14 and day 19 of embryonal development and at day 1 post hatching. Hepatocytes were exposed in vitro to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126, IUPAC nomenclature) and 2,3',4,4',5-pentachlorobiphenyl (PCB 118). The respective compounds were chosen as representatives for dioxins, furans, non-ortho PCBs, and mono-ortho PCBs. These groups of chemicals have been identified as environmental contaminants with major dioxin-like effects that are mediated by a common receptor, the arylhydrocarbon (Ah) receptor. At all developmental stages, TCDF was more potent than TCDD. Relative potencies (RP = EC50TCDD/EC50HAH) decreased in the order TCDF < TCDD < PCB 126 < PCB 118. Depending on the developmental stage, TCDF was 1.2 to 3.4 times more potent than TCDD. PCB 126 was equipotent or less potent by a factor of 3 than TCDD. PCB 118 was 100 to 300 times less potent than TCDD. Both the mean effective concentration (EC50) and the maximum EROD activity (Ymax) of all compounds were lower in hepatocyte cultures from 14-day-old embryos than those from 19-day-old embryos or 1-day-old hatchlings. RPs were comparable in 19-day-old embryos and in hatchlings, but significantly different in 14-day-old embryos.

Animals↗
PubMed1997

Sensitivity of common tern (Sterna hirundo) embryo HepatocyteCultures to CYP1A induction and porphyrin accumulation by halogenated aromatic hydrocarbons and common tern egg extracts.

Experiments were conducted to compare the sensitivity ofprimary cultures of common tern (Sterna hirundo) and chicken(Gallus domesticus) embryo hepatocytes to cytochrome P4501A (CYP1A)induction and porphyrin accumulation after exposure to halogenated aromatichydrocarbons (HAHs) or tern egg extracts. The HAHs tested were2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD),2,3,7, 8-tetrachlorodibenzofuran (TCDF) 3,3',4,4'-tetrachlorobiphenyl (PCB 77;IUPAC nomenclature), 3,3',4,4',5-pentachlorobiphenyl (PCB 126),3, 3',4,4',5,5'-hexachlorobiphenyl (PCB 169) and Aroclor(R) 1254 (a commercialmixture of PCBs). Extracts were prepared from common tern eggs collected fromthree sites in the Great Lakes basin and one reference site on the east coastof Canada. CYP1A induction was assayed asethoxyresorufin-O-deethylase (EROD) activity and/or immunodetectableCYP1A protein, and total intracellular porphyrin accumulation was measuredfluorometrically. Unlike chicken embryo hepatocyte (CEH) cultures, nointracellular porphyrin accumulation was observed after treatment of ternembryo hepatocyte (TEH) cultures with HAHs or egg extracts. TEH cultures were approximately 50 to >1600 times less sensitive than CEH cultures to HAH-mediated CYP1Ainduction. In contrast, TEH cultures were either approximately equallysensitive or only 3.5-15 times less sensitive than CEH cultures to CYP1Ainduction mediated by tern egg extracts. These data suggest that common ternembryos may be more susceptible to the CYP1A inducing effects mediated bycomplex mixtures of environmental contaminants than indicated by theirresponse to individual HAHs.

Animals↗
PubMed1997

Comparative toxicity of polychlorinated biphenyls to Japanese quail (Coturnix c. japonica) and American kestrels (Falco sparverius).

Polychlorinated biphenyls (PCBs) and related halogenated hydrocarbons bioaccumulate to high concentrations in top predators, such as raptorial birds, yet little is known of PCB toxicity to such species. This study explored several aspects of both the acute and chronic response of American kestrels (Falco sparverius) to three purified PCB congeners and a commercial mixture, Aroclor 1254, and compared the response to that of the Japanese quail (Coturnix c. japonica), a more studied species known to be PCB sensitive. In one experiment, adult female birds were given single oral doses of either Aroclor 1254, 3,3',4,4'-TCB (PCB 77, IUPAC nomenclature), 3,3',4,4',5-PCB (PCB 126) or 2,2',4,4',5,5'-HCB (PCB 153) and sacrificed after 5 d. In kestrels, neither the pure compounds nor the mixture affected hepatic or renal porphyrin levels. There was slight but significant hepatic and renal ethoxyresorufin O-deethylase (EROD) induction in birds dosed with PCBs 77 and 126. A cytochrome P-4501A (CYP1A) cross-reactive protein was detected in liver and kidney of kestrels given PCBs 77 and 126, but not in Aroclor 1254-dosed birds. In quail, an acute dose of Aroclor 1254 caused significant liver weight increases, hepatic and renal EROD and aminopyrine n-demethylase (APND) induction, and dose-related hepatic and renal porphyria. Quail treated with PCB 126 developed hepatic and renal porphyria; EROD and APND were also induced. Administration of PCB 77 caused only slight induction of hepatic EROD activity. PCB 153 caused some hepatic and renal porphyria and induced EROD to the same degree as PCB 126. A hepatic CYP1A cross-reactive protein was induced about 200-fold in all individual quail that exhibited significant EROD induction and was also induced in kidney of 1 quail given Aroclor 1254. A second experiment examined chronic exposure to Aroclor 1254 by feeding adult females of both species a daily dose of 7 mg/kg/d for 4-, 8-, and 12-wk periods. There were no effects on hepatic porphyrins in kestrels. APND and aldrin epoxidase (AE) were induced; EROD was not induced, although a hepatic CYP1A-like protein was detected in 1 kestrel dosed for 12 wk. Chronic exposure of quail to Aroclor 1254 caused highly significant increases in mean hepatic porphyrin levels and in activity of EROD, APND, and 4-chlorobiphenyl hydroxylase; a CYP1A-like protein was also induced about 200-fold. In both studies, Aroclor 1254 residues accumulated in tissues of both species, but there was no significant relationship between residue levels and effects. In conclusion, adult American kestrels were relatively insensitive to the effects of PCBs, from both acute and chronic exposure, on hepatic and renal porphyrin levels. Although concentrations of a CYP1A-like protein were increased in some kestrels given PCBs, EROD activity was only marginally increased, suggesting that catalytic activity of this protein differed among the two species.

Aminopyrine N-Demethylase↗
PubMed1996

Toxicity of 2,4,4'-trichlorobiphenyl in rats following 90-day dietary exposure.

The toxicity of 2,4,4'-trichlorobiphenyl (PCB 28) was investigated in rats after a 90-d dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 28 in the diet at 0, 0.05, 0.50, 5.0, or 50.0 ppm for 13 wk. Growth rate and food consumption were not affected by treatment, and no clinical signs of toxicity were observed. Mottled liver was noted in both control and PCB-treated males, but was found with increased incidence in the highest treatment group. Increased urinary ascorbic acid and hepatic microsomal ethoxyresorufin O-deethylase activity were observed in the 50.0 ppm group of both sexes. The vitamin A content in liver, lung, and kidney was not significantly affected by treatment. Analysis of brain biogenic amines showed a decreased dopamine concentration in the substantia nigra region of female rats receiving 0.5 ppm PCB 28 and higher doses. Female rats appeared to be more sensitive than males to the neurochemical effects of PCB 28. Dose-dependent histologic changes were observed in the thyroid and liver, with biologically significant changes occurring at 5.0 ppm and above. Based on these data, the no observable-adverse-effect level (NOAEL) for this PCB congener was considered to be 0.5 ppm in diet or 36 micrograms/kg body weight/d.

Administration, Oral↗
PubMed1996

Cytochrome P4501A induction in avian hepatocyte cultures: a promising approach for predicting the sensitivity of avian species to toxic effects of halogenated aromatic hydrocarbons.

Concentration-dependent effects of halogenated aromatic hydrocarbons (HAHs) on cytochrome P4501A (CYP1A) induction in primary hepatocyte cultures prepared from embryos of chickens (four breeds), pheasants, turkeys, ducks (three breeds), and herring gulls were determined. CYP1A activity was estimated by measuring ethoxyresorufin O-deethylase (EROD) activity and the concentration of immunodetectable CYP1A was estimated using mouse monoclonal antibody 1-12-3 that was prepared against scup (Stenotomus chrysops) CYP1A1. The HAHs studies were 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4'-tetrachlorobiphenyl (PCB 77, IUPAC nomenclature), 3,4,4',5-tetrachlorobiphenyl (PCB 81), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169), 2,3,3',4,4'-pentachlorobiphenyl (PCB 105), and 2,3',4,4',5-pentachlorobiphenyl (PCB 118). Two general types of comparisons were made: (1) relative potencies of compounds within a species (expressed relative to TCDD as induction equivalency factors, IEFs) and (2) relative sensitivity of each species to EROD induction by each compound. Three methods for estimating potency were compared. These were: (1) the concentration of inducer that produced a half-maximal (EC50) EROD response, (2) the concentration producing a response equivalent to 10% of the maximal response produced by TCDD (ECTCDD 10%), and (3) a slope ratio method. For each method, the rank order in potency was TCDD > or = TCDF > PCB 126 > PCB 81 > PCB 77 > PCB 169 in chicken, pheasant, and turkey hepatocytes. The rank order was similar in duck and herring gull hepatocytes with the following exceptions: TCDF was approximately 2- to 4-fold more potent than TCDD in duck hepatocytes; PCB 169 induced EROD in gulls, but PCB 77 had no measurable effect in this species. PCB 118 was a relatively weak EROD inducer in most species/breeds, but it did not induce EROD in Pekin ducks or gulls. PCB 105 was a weak inducer in White Leghorn chicken and turkey hepatocytes, but it did not induce EROD in other species. The EC50, ECTCDD10% and slope ratio methods for estimating potencies generally gave similar IEFs for compounds that produced a maximal response that was at least 60% of the maximal response produced by TCDD. For compounds that caused a response that was 50% or lower than that produced by TCDD, EC50-based IEFs were greater (10- to 100-fold) than ECTCDD10%-based IEFs or slope-ratio-based IEFs. Among species, the rank order in sensitivity to EROD induction was chicken > pheasant > turkey > or = duck > or = herring gull. The relative sensitivity of avian hepatocyte cultures to EROD induction by PCB 77 was similar to the relative sensitivity of these species (reported elsewhere) to lethality after in ovo injection of PCB 77. Chicken hepatocyte cultures were 5-10 times more sensitive to EROD induction by TCDD than were pheasant hepatocyte cultures, which is identical to the difference in sensitivity of these species to the lethal effect of TCDD after in ovo injection. Measuring the sensitivity of hepatocyte cultures to EROD induction might be useful for estimating the sensitivity of avian species (including rare or endangered species, where it is impossible to conduct in vivo studies) to the embryotoxic effects of TCDD, non-ortho substituted PCBs, and other aryl hydrocarbon receptor agonists.

Animals↗
PubMed1995

Efficient analysis of cytochrome P4501A catalytic activity, porphyrins, and total proteins in chicken embryo hepatocyte cultures with a fluorescence plate reader.

An efficient method for measuring polychlorinated biphenyl-mediated induction of cytochrome P4501A, using the ethoxyresorufin-O-deethylase (EROD) assay, and total porphyrins in chicken embryo hepatocyte cultures is described. Hepatocytes were cultured in 48-well plates, assays were carried out within the wells, and concentrations of the product of the EROD reaction (resorufin), porphyrins, and total proteins were measured in the same wells with a fluorescence plate reader. The method differs from previous methods developed in this laboratory in that three fluorophors were measured in the same well rather than two.

Animals↗
PubMed1995

Toxicity of PCB 77 (3,3',4,4'-tetrachlorobiphenyl) and PCB 118 (2,3',4,4'5-pentachlorobiphenyl) in the rat following subchronic dietary exposure.

The toxicity of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and 2,3',4,4',5-pentachlorobiphenyl (PCB 118) was investigated in rats following subchronic dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 77 in the diet at 0, 10, 100, 1000, or 10,000 ppb for 13 weeks. PCB 118 was administered to males in the diet at 0, 10, 100, 1000, and 10,000 ppb, while the female groups received 0, 2, 20, 200, or 2000 ppb of the congener for 13 weeks. Growth rate and food consumption were not affected by treatment. No clinical signs of toxicity were observed. Increased spleen weight occurred in male rats fed 1000 or 10,000 ppb PCB 77. Male rats receiving 10,000 ppb PCB 118 had increased liver weight and hepatic ethoxyresorufin O-deethylase (EROD) activity. Increased hepatic EROD activity but not liver weight was observed in female rats given the 2000-ppb PCB 118 diet. Increased EROD activity was also noted in male rats given 10,000 ppb and in female groups receiving 1000 or 10,000 ppb PCB 77. Male rats exposed to 10,000 ppb PCB 77 had decreased vitamin A in the liver and lung and elevated levels in the kidney. Liver vitamin A of both 1000- and 10,000-ppb PCB 77 female groups was decreased. PCB 118 had no effects on tissue vitamin A at the levels studied. No hematological changes or serum biochemical changes were seen in any of PCB 118- and PCB 77-treated groups, nor were liver uroporphyrin levels altered. A reduction in dopamine and homovanillinic acid in substantia nigra region of the brain was observed in female rats fed 2000 ppb PCB 118, while 10,000 ppb PCB 77 was associated with an elevation in 3,4-dihydroxyphenylacetic acid in the nucleus accumbens region of male rat brains. Mild to moderate changes were observed in the liver and thyroid of rats given PCB 77 or PCB 118. PCB 118 accumulated in a dose-dependent manner in fat and to a much lesser extent in liver. In contrast, very low levels of PCB 77 residue were found in the tissues examined. Based on the above data it was concluded that NOAEL of PCB 77 is 100 ppb in diet or 8.7 micrograms/kg and that of PCB 118 is 200 ppb in diet or 17 micrograms/kg body wt/day.

Animal Feed↗
PubMed1994

Simultaneous measurement of cytochrome P4501A catalytic activity and total protein concentration with a fluorescence plate reader.

A method for simultaneous measurement of the cytochrome P4501A-associated enzyme, ethoxyresorufin-O-deethylase (EROD), and total protein concentration in liver microsomes is described. EROD assays were carried out in multiwell plates, and the fluorescent product (resorufin) and total proteins were quantified within the same wells with a fluorescence plate reader. Fluorescamine was used for protein assays.

Animals↗
PubMed1994

Subchronic toxicity of 3,3',4,4',5-pentachlorobiphenyl in the rat. I. Clinical, biochemical, hematological, and histopathological changes.

The systemic toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) following subchronic dietary exposure was investigated in Sprague-Dawley rats. PCB 126 was administered to rats of both sexes at concentrations of 0.1, 1.0, 10, or 100 ppb in their diet for 13 weeks. Another group of rats received a loading dose of 5 micrograms PCB/kg body wt at the start of the feeding period followed by exposure to 10 ppb PCB diet for the same period of time as the other groups. Growth suppression and decreased food consumption were observed in the highest dose groups of both sexes. Increased organ/body weight ratios for the liver occurred in the 10 and 100 ppb groups of both sexes. Rats of both sexes exposed to the highest dose of the PCB also exhibited increased relative kidney, spleen, and brain weights. Hematological and most serum biochemical changes were confined to the 100 ppb groups. These included elevated alkaline phosphatase, bilirubin, cholesterol, and aspartate aminotransferase, and decreased serum glucose, hemoglobin, erythrocytes, hematocrit, and platelets. A dose-dependent increase in liver ethoxyresorufin-O-deethylase activity was observed in rats of both sexes starting at 0.1 ppb. A dose-dependent increase in liver uroporphyrin levels was observed in both sexes and significant changes occurred in the female rats at 1.0 ppb and higher dose groups. Decreased liver vitamin A was observed in the 10 ppb group and higher in both sexes. Kidney vitamin A was elevated in the 100 ppb group. No statistically significant changes were noted in concentrations of brain biogenic amines. PCB 126 residues were 10-fold higher in liver than in fat. Treatment-related histopathological changes were observed in the thymus, thyroid, bone marrow, and liver of rats exposed to the 10 ppb diet, but increased frequency of mild changes was observed in most of these tissues at the 1.0 ppb level. Based on the above data, the no adverse effect level was judged to be 0.1 ppb in the diet or 0.01 micrograms/kg body wt/day.

Animals↗
PubMed1994

Efficacy of domperidone and sulpiride as treatments for fescue toxicosis in horses.

We evaluated the effectiveness of 2 dopamine antagonists as treatments for fescue toxicosis in horses. Sixteen gravid mares were assigned by breed and expected foaling date to 1 of 3 treatment groups: endophyte-infested control; 1.1 mg of domperidone/kg of body weight/d; and 3.3 mg of sulpiride/kg/d. Mares were pastured on endophyte-infected fescue and received 0.454 kg of a corn and dried molasses carrier containing the drug treatment. Treatment started 30 days prior to expected foaling date and continued until parturition. Blood samples were collected, and mammary gland scores were recorded every 5 days. Body weight and body condition scores were obtained every 28 days. Serum was analyzed for prolactin, progesterone, and estradiol-17 beta concentrations. Domperidone-treated mares had shorter (P = 0.09) gestation duration and foaled closer (P = 0.07) to their expected parturition date than did control mares. Mammary gland scores were higher (P < 0.05) for domperidone-treated mares than for control mares. By 4 and 9 days after the start of treatment, serum prolactin concentration was higher (P < 0.05) in domperidone-treated mares and sulpiride-treated mares, respectively, than in control mares. Domperidone- and sulpiride-treated mares had higher (P < 0.05) serum progesterone and lower (P < 0.01) estradiol-17 beta concentrations than did control mares. These results indicate that domperidone may offer considerable potential as a treatment for fescue toxicosis in horses.

Animal Feed↗
PubMed1993

Improved method to extract and concentrate porphyrins from liver tissue for analysis by high-performance liquid chromatography.

A new method to extract and concentrate porphyrins from liver tissue for analysis by high-performance liquid chromatography is described. Porphyrins were extracted with acetonitrile-hydrochloric acid, concentrated on disposable octadecylsilyl columns, brought to dryness, and reconstituted in 1.2 M hydrochloric acid. Dried porphyrins were stable at -80 degrees C for at least three weeks, and porphyrins reconstituted in hydrochloric acid were stable for at least 20 h. Yields of uro-, heptacarboxyl-, hexacarboxyl-, pentacarboxyl- and coproporphyrin were > or = 90%. The method allows determination of porphyrin concentrations in small (10-100 mg) samples of liver tissue.

Acetonitriles↗
PubMed1993

Ethoxyresorufin-O-deethylase and porphyrin analysis in chicken embryo hepatocyte cultures with a fluorescence multiwell plate reader.

Rapid and sensitive methods for measuring ethoxyresorufin-O-deethylase (EROD) induction and total intracellular porphyrin accumulation in cultured chicken embryo hepatocytes exposed to polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are described. Cells were cultured in 48-well cell culture plates, and EROD assays were carried out directly within the wells. EROD activity and porphyrin concentrations were determined with a computer-operated fluorescence multiwell plate reader. Porphyrin and EROD assays could be carried out on the same plates or on separate plates. The assays allow one to obtain dose-response curves at rates that are approximately 100 times faster than conventional methods.

Animals↗