Biomedical subjects

P R Cheeke

Publications and source records attributed to P R Cheeke.

At least 37 records · Page 2Linked to original sources

PubMed1988

Toxicity and metabolism of pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PA) are found mainly in plants of three families: boraginaceae, Compositae and Leguminosae. In North America, PA poisoning of livestock is caused primarily by consumption of Senecio and Crotalaria spp. The PA of Senecio spp. cause irreversible hepatic damage; toxicity signs are a consequence of impaired liver function. Crotalaria intoxication leads to pulmonary damage as a primary effect; hepatic effects are less prominent. Large species differences exist in susceptibility to PA toxicosis. Small herbivores such as sheep, goats, rabbits, guinea pigs and other herbivorous laboratory animals are highly resistant to PA toxicity, associated with a low rate of hepatic production of reactive metabolites (pyrroles) and(or) a high rate of activity of detoxifying enzymes. Diester PA common to Heliotropium and Echium spp. are metabolized in the ovine rumen to 1-methyl metabolites, whereas the macrocyclic ester PA of Senecio spp. are not. Exposure to PA results in high concentrations of liver Cu, reduced liver Zn, and abnormal Fe metabolism with hematopoiesis markedly impaired. Pyrrolizidine alkaloid toxicity alters vitamin A metabolism in rats, depressing plasma and liver levels of vitamin A. Synthetic antioxidants in the diet confer protective activity in laboratory animals (e.g., rats, mice) against PA toxicoses. The PA and their metabolites are secreted in the milk of lactating animals, but this probably does not represent a significant human health hazard.

Animals↗

PubMed1988

Effects of dietary butylated hydroxyanisole and cysteine on toxicity of Lathyrus odoratus to broiler and Japanese quail chicks.

The effect of .75% dietary butylated hydroxyanisole (BHA) and 1% cysteine on the toxicity of Lathyrus odoratus seed to Japanese quail and broiler chicks was examined. In both species, the feeding of Lathyrus seed as a component of a complete diet depressed (P less than .05) body weight gain and feed intake. Typical signs of lathyrism, including ruffled feathers, enlarged hocks, curled toes, ataxia, leg paralysis, and mortality, were observed. Neither BHA nor cysteine exerted protective effects against the lathyrogenic effects. As assessed by mortality, these additives appeared instead to potentiate Lathyrus toxicity.

Animals↗

PubMed1986

Growth and reproductive performance of rabbits on a moderately low crude protein diet with or without methionine or urea supplementation.

The reproductive and growth performances of New Zealand White rabbits on four dietary treatments were compared. The treatments were a 21.5% crude protein (CP) diet control, a 16% CP diet (LP), LP + .3% DL-methionine (LP + met) and LP + 2.1% urea (LP + urea). The CP in the LP diet was derived entirely from alfalfa meal and wheat mill run, with no protein supplement used. Data were collected over five parities. Preweaning and postweaning growth rates and reproductive performance as assessed by litter size, conception rate and litter interval, were comparable for the four treatments. Average daily postweaning gain was about 40 g per d. Litter size at weaning was seven kits per litter. This study indicates that a simple diet of forage and a grain-milling by-product, with no cereal grain or protein supplement, can support normal growth and reproduction of commercial meat rabbits.

Animals↗

PubMed1985

Effect of dietary crude protein level on the reproductive performance and growth of New Zealand white rabbits.

An experiment utilizing 391 preweaning and 187 postweaning litter records from 145 does was conducted for 12 mo to determine the effect of dietary crude protein level on performance of commercial New Zealand White rabbits. Does and their litters were fed alfalfa-based pelleted diets containing either 17.5, 19 or 20.5% crude protein (CP). In a separate experiment, the 17.5 and 20.5% CP diets were fed during lactation to 10 does to determine nitrogen (N) digestibility and retention. Body weights of does fed 17.5% CP were lower (P less than .01) than for the other treatments after 21 and 28 d of lactation. No differences (P greater than .10) were observed for doe weight at kindling, percentage fertility, litter size, preweaning litter mortality, 1- to 21-d consumption, preweaning feed efficiency and 28- to 56-d average daily consumption, average daily gain and average weight. Total born tended to be higher (P = .07) on higher protein levels but percentage born alive was greatest (P less than .01) on the 17.5% CP diet. Does fed 19% CP tended to have a greater number of parities (P = .06). Other significant differences observed for preweaning litter traits were between 17.5 and 19% CP groups. Does fed 19% CP had heavier litters at birth (P less than .01), at 21 d (P = .05) and 28 d (P = .06) and had greater 1- to 21-d litter gains and 21- to 28-d consumption (P = .05) than those fed 17.5% CP. For postweaning performance, feed efficiency values were lowest and mortality was highest for litters fed 20.5% CP. When litters were switched to different diets after weaning, mortality tended to be higher (P = .07) for animals that were fed 20.5% CP before weaning. The month of experiment effect did not influence any of the characters studied (P greater than .05). Parity number was important for percentage fertility, percentage born alive, litter birth weight and doe weight at 21 and 28 d (P less than .05). Does at first parity showed the poorest performance for all traits (except percentage fertility). Fertility fluctuated throughout the first four parities and then steadily declined. Does fed 20.5% CP had greater apparent dry matter and acid detergent fiber digestibilities and N intakes (P less than .05) and retained 90% more N during lactation (P = .22) than does fed 17.5% CP. Milk production and CP digestibility did not differ between the two diets tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Effects of dietary supplementation with ethoxyquin, magnesium oxide, methionine hydroxy analog, and B vitamins on tansy ragwort (Senecio jacobaea) toxicosis in beef cattle.

Dried tansy ragwort containing pyrrolizidine alkaloids was fed as 2.5% of a complete (control) diet to Hereford steers, with and without (basal) a mixture of additives. The additives provided a dietary supplement equivalent to 0.1% ethoxyquin, 1% methionine hydroxy analog, 2% MgO, 2.7 mg of vitamin B6/kg of diet, 50 micrograms of vitamin B12/kg of diet, 0.45 g of folic acid/kg of diet, and 0.2 g of cobalt/kg of diet. The additives did not alter tansy ragwort toxicity substantially, as assessed by liver histologic changes, sulfobromophthalein clearance rate, and serum gamma-glutamyl transpeptidase activity. After 281 days, 1 of 4 steers fed the basal diet was alive, whereas 3 of 4 steers in the basal plus additives group were alive, suggesting some protective activity. The chronic lethal dose of tansy ragwort in steers was 3.6% of initial body weight.

Animals↗

PubMed1984

Evaluation of amino acids, B vitamins and butylated hydroxyanisole as protective agents against pyrrolizidine alkaloid toxicity in rats.

Supplementation of the diets of rats with branched chain amino acids (BCAA: leucine, isoleucine, valine) did not alter their susceptibility to chronic poisoning by tansy ragwort (Senecio jacobaea), which contains hepatotoxic pyrrolizidine alkaloids (PA). Phenobarbital in the diet, which alters liver microsomal enzyme activity, also did not alter susceptibility to PA poisoning. A combination of butylated hydroxyanisole (BHA), cysteine and BCAA did increase (P less than .05) survival time of rats fed tansy ragwort. Dietary BHA and cysteine increased the survival time of rats injected with the PA monocrotaline, with evidence that addition of vitamin B12 and folic acid improved the effectiveness of this treatment. In a chronic feeding trial with tansy ragwort, a combination of BHA and cysteine increased (P less than .05) the survival times of rats, showing protective activity against PA poisoning. A mixture of B-complex vitamins, or vitamin B12-folic acid, was not effective in improving the response.

Amino Acids↗

PubMed1984

Mutagenic responses of tansy ragwort (Senecio jacobaea) plant, pyrrolizidine alkaloids and metabolites in goat milk with the Salmonella/mammalian-microsome mutagenicity test.

Tansy ragwort (Senecio jacobaea ) was evaluated for animal and human health hazard using the Salmonella/mammalian-microsome mutagenicity test. An acetone extract of tansy ragwort (TR) produced a negative mutagenic response for bacterial tester strains TA1535 and TA100 and a toxic response in tester strains TA1537 and TA98. Assay of this extract in the presence of mammalian liver microsomes (S-9) resulted in positive mutagenic responses in tester strains TA1535, TA1537, TA98 and TA100. Species differences were evaluated by use of liver microsome preparations from induced rat and uninduced sheep, beef, hamster, trout and rat. Only a slight species difference was demonstrated. A mixture of pyrrolizidine alkaloids (PA), extracted from TR flowers, produced a negative response in tester strains TA1535, TA1537, TA98 and TA100. A negative response was also demonstrated when the TR flower PA mixture was assayed with the Salmonella tester strains and induced rat liver microsomes ( IRLM ). A mixture of PA extracted from Senecio longilobus also produced a negative response. The major PA present in TR, jacobine , produced a negative response without and with IRLM exposure in tester strains TA1535, TA1537, TA98 and TA100. Another similar PA, monocrotaline, found in various Crotalaria species also gave a negative response. Milk from TR-fed goats was evaluated for mutagenic response. Milk from goats not receiving TR and from goats receiving TR at a level of 1% of their body weight/day via rumen cannula produced a negative response without liver microsomes present. Milk from TR-fed goats, however, yielded both negative and marginally positive responses for different combinations of tester strains and liver microsome preparations.

Animals↗

PubMed1984

The effect of consumption of the pyrrolizidine alkaloid-containing plant Senecio jacobaea on iron and copper metabolism in the rat.

The effect of dietary tansy ragwort (Senecio jacobaea), a pyrrolizidine alkaloid (PA)-containing plant, on mineral metabolism in rats was studied. In experiment 1, rats were fed a dietary level of 5% tansy ragwort. At intervals of 1, 2, 4, 6 and 8 weeks animals were killed and tissue mineral levels determined. As compared to comparable controls, rats fed tansy ragwort showed by 6 weeks elevated liver and spleen copper and iron levels. Experiment 2 was a 3 X 4 factorial experiment with added dietary copper levels of 0, 50 and 250 ppm, and tansy ragwort levels of 0, 1, 2.5 and 5%. Liver copper levels increased markedly with increasing levels of tansy ragwort; at 0, 50 and 250 ppm added copper, liver copper levels were 4, 18 and 21 times greater in rats fed 5% tansy ragwort as compared to those with no tansy ragwort. Increases in liver iron and spleen copper were noted with consumption of tansy ragwort. Higher liver copper levels were observed when a casein-based diet rather than a soybean meal diet was used, suggesting an effect of phytate in soybean meal in reducing copper absorption. In the last experiment, 59Fe was administered to rats fed diets with or without tansy ragwort. After 5 weeks on tansy ragwort, rats showed very low levels of 59Fe in erythrocytes, tibia and liver, and elevated levels in spleen and kidney, suggesting either an impairment of hematopoesis or accelerated erythrocyte destruction as a result of PA consumption. These results indicate that PA's cause increased liver copper content, and disturbances in iron metabolism.

Animals↗

PubMed1984

Effects of dietary copper and molybdenum on tansy ragwort (Senecio jacobaea) toxicity in sheep.

Dried tansy ragwort (Senecio jacobaea), which contains pyrrolizidine alkaloids (PA), was fed to sheep to determine whether PA consumption influenced liver Cu concentrations. Nine Polypay wether lambs were allotted to 3 groups according to the diets: control diet + 50 micrograms of Cu/g of feed (control + Cu); tansy ragwort (TR) diet + 50 micrograms of Cu/g of feed (TR + Cu); and TR diet + 50 micrograms of Cu/g of feed and 10 micrograms of Mo/g of feed (TR + Cu + Mo). Liver Cu concentrations were sharply increased (13-fold) after 8 weeks of feeding the diets, and then decreased slightly. There were no significant differences in concentrations of liver Cu among treatment groups. All lambs in the group fed TR + Cu + Mo died by the end of 23 weeks, with the usual signs of PA poisoning, including liver necrosis, hepatic megalocytosis, and biliary hyperplasia. The TR intake was about 2.7 to 3.0 kg/kg of their initial body weight. All lambs in the group fed the control + Cu diet survived. The results indicated that sheep fed TR do not preferentially accumulate liver Cu. There was an indication that dietary Mo increased susceptibility to TR intoxication.

Animal Feed↗

PubMed1984

Effects of dietary supplementation with butylated hydroxyanisole, cysteine, and vitamins B on tansy ragwort (Senecio jacobaea) toxicosis in ponies.

Dried tansy ragwort, which contains pyrrolizidine alkaloids, was fed as 10% of a complete diet to ponies, with and without a mixture of additives. The additives provided a dietary supplement equivalent to 1% cysteine, 0.75% butylated hydroxyanisole, 200 micrograms of vitamin B12/kg of feed, and 5 mg of folic acid/kg of feed. The additives did not alter tansy ragwort toxicity, as assessed by survival time, liver changes, sulfobromophthalein (BSP) clearance rate, serum gamma-glutamyl transpeptidase activity, and plasma amino acid patterns. In ponies fed tansy ragwort, BSP clearance rate was a sensitive indicator of liver damage, and decreased to about 20% of control values. gamma-Glutamyl transpeptidase activities showed considerable variability, but generally were elevated in animals fed tansy ragwort. Liver iron and copper concentrations increased, and liver zinc concentrations decreased in tansy ragwort-fed ponies. Plasma amino acid patterns in tansy ragwort-fed ponies showed changes typical of those observed in liver disease.

Animal Feed↗

PubMed1983

Toxicity of Senecio jacobaea and pyrrolizidine alkaloids in various laboratory animals and avian species.

The chronic toxicity of tansy ragwort (Senecio jacobaea) to several herbivorous laboratory animals and to chicks and turkey poults was examined by feeding the dried plant as a component of a mixed diet. Gerbils, hamsters and guinea pigs were resistant to chronic toxicity. Gerbils were highly resistant, consuming over 3500% of their body weight of the dried plant, whereas susceptible species succumb to a tansy ragwort intake of 5-20% of their body weight. Guinea pigs and gerbils were resistant to acute toxicity of injected monocrotaline, a pyrrolizidine alkaloid (PA). They were moderately resistant to acute toxicity of injected tansy ragwort alkaloids. Both chicks and turkey poults were susceptible to chronic toxicity of dietary tansy ragwort.

Animals↗

PubMed1983

Comparison of the toxicities of Senecio jacobaea, Senecio vulgaris and Senecio glabellus in rats.

The toxicity of Senecio jacobaea, S. vulgaris and S. glabellus to rats was assessed in a feeding trial. The plants were of similar toxicity, with a plant dry matter intake of about 20% of initial body weight being a lethal dose. Gas chromatography-mass spectrometry analysis demonstrated the presence of seneciphylline, jacobine, jacozine and jacoline in S. jacobaea, senecionine and seneciphylline in S. vulgaris, and senecionine in S. glabellus. An unidentified alkaloid was also found in all three plants.

Animals↗

PubMed1983

An evaluation of acetone extracts from six plants in the Ames mutagenicity test.

Acetone extracts from six plants were evaluated for mutagenic activity with the Salmonella/mammalian-microsome mutagenicity test (Ames) utilizing tester strains TA98 and TA100 and in the presence and absence of induced rat liver microsomes. Extracts from alfalfa (Medicago sativa), lettuce (Lactuca sativa) and thread-leaf groundsel (Senecio longilobus) produced only negative responses. Comfrey (Symphytum officinale) and tansy ragwort (Senecio jacobaea) extracts produced toxic responses that were abolished in the presence of the microsomal bioactivation system. Bracken (Pteridium aquilinum) and tansy ragwort extracts produced positive responses following bioactivation with the liver microsomal system. The results suggest that the Ames mutagenicity test may be of some value in initial evaluations for potential toxic effects of plants consumed by animals and man.

Acetone↗

PubMed1983

Effect of sheep rumen fermentation and methane inhibition on the toxicity of Senecio jacobaea.

Senecio jacobaea (SJ) was incubated in sheep rumen fluid-buffer mixtures to determine if metabolism and(or) detoxication of pyrrolizidine alkaloids (PA) was occurring. The nontoxic reduction metabolite, 7 beta-hydroxy-l-methylene-8 alpha-pyrrolizidine, was not detected when SJ-rumen fluid incubation extracts were subjected to high performance liquid chromatography and mass spectrographic analysis. Rats were used as assay animals in another experiment to assess the toxicity of SJ incubated in rumen fluid. Incubation treatments were: Rumen fluid (RF) from a sheep not fed SJ (RF-0); RF autoclaved before incubation (RF-0A); RF from sheep fed 50% SJ for 1 wk (RF-1); RF from a sheep fed 50% SJ for 5 wk (RF-5), and RF-5 with 5 microM iodoform in the incubation medium (RF-5I). The SJ treatments were included in rat diets at the 10% level. Dietary treatment and mean rat survival times (days) were: control, no mortality; 10% untreated SJ, 43; RF-0, 53; RF-0A, 55; RF-1, 44; RF-5, 56; RF-5I, 44, There were no significant differences in survival time. This indicates that SJ was not detoxified as a result of incubation in sheep RF in vitro, and suggests that rumen detoxification does not account for resistance of sheep to SJ. The pH and volatile fatty acid concentrations of the incubation mixtures were measured before and after incubation. Acetate/propionate and pH following incubation were respectively: RF-0A, 7.3, 4.3; RF-0, 4.2, 4.4; RF-1, 2.7, 4.5; RF-5, 2.6, 4.5; RF-5I, 2.4, 4.5. These data show that although pretreatment of the rumen fluid donor with dietary SJ and addition of iodoform to the incubation mixture favor reductive rumen metabolism, detoxification of PA from SJ does not occur during in vitro sheep rumen fermentation.

Animals↗

PubMed1983

Effect of phenobarbital on toxicity of pyrrolizidine (Senecio) alkaloids in sheep.

The effect of prolonged phenobarbital (PB) administration on the toxicity of Senecio jacobaea (SJ) was studied in sheep. Hepatic microsomal mixed function oxidase (MFO) activity was monitored. Pentobarbital sleeping times were decreased after 17 d of treatment, indicating initial induction of MFO. At 105 d of treatment, hepatic microsomal aminopyrine N-demethylase activity and cytochrome P-450 levels were increased (P less than .05) as a result of PB administration. No differences (P greater than .05) were observed in activity of microsomal epoxide hydrolase, glutathione S-transferase or liver glutathione as a result of SJ and (or) PB. Epoxide hydrolase activity in control sheep was about fivefold higher than values previously reported for rats. Liver Cu concentration was increased (P less than .05) in sheep receiving PB and SJ when compared with controls, but no differences (P greater than .05) were observed in the hepatic intracellular distribution of Cu as a result of PB and(or) SJ. Histopathological examination of liver revealed greater incidence and severity of lesions in animals receiving SJ, but PB did not appear to potentiate SJ intoxication. The results suggest that MFO induction by PB does not increase the susceptibility of sheep to SJ intoxication. Sheep possess a high activity of hepatic microsomal epoxide hydrolase which could account for their resistance to SJ intoxication.

Aminopyrine N-Demethylase↗

PubMed1983

Doe reproduction and preweaning litter performance of straightbred and crossbred rabbits.

Reproductive characters (N = 430 matings) of four doe genetic groups and preweaning performance of litters (N = 280) were evaluated in a 15-mo study. Doe genetic groups were New Zealand White (NN) and Californian (CC) straightbreds and Californian X New Zealand White (CN) and New Zealand White X Californian (NC) crossbreds. Does and litters were provided either a commercial control or a 74% alfalfa pelleted diet. Sires of litters included NN, CC and Flemish Giant (FG) straightbred bucks. The linear and quadratic regression on age of dam affected (P less than .01) litter birth weight. The NN does were heavier than CC does at first breeding at 154 d and produced heavier litters at birth and weaning (all P less than .01). Percentage survival of kits from birth to weaning and doe and preweaning litter feed intake and efficiency were greater from NN than CC does (all P less than .01). Numbers born and reared/litter to weaning at 28 d were likewise greater for NN vs CC straightbred does. Heterosis estimated from comparing litters of reciprocal crossbred vs straightbred does was significant for number born, litter birth and weaning weights and doe and preweaning litter feed intake. Reciprocal crossbred differences were observed (P less than .05) for doe breeding weight, number born and weaned per litter, litter birth and weaning weights and doe and preweaning litter feed intake, favoring CN does reared by NN straightbred dams over NC does. Diet, in consistent favor of the 74% alfalfa diet, significantly affected all traits studied with the exception of doe longevity, doe fertility percentage, and doe and litter feed efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1983

Characterization of straightbred and crossbred rabbits for milk production and associative traits.

Two hundred twenty-five lactation and litter performance records from 82 does representing four genetic groups and two diets were analyzed to quantify breed, heterosis, reciprocal F1 cross and diet effects for milk production and associative traits. Doe genetic groups were New Zealand White (NN) and Californian (CC) straightbred and Californian X New Zealand White (CN) and New Zealand White X Californian (NC) reciprocal crossbreds. Pelleted diets fed to does and litters were either a commercial control or a 74% alfalfa diet. Three sire breeds of litters included NN, CC and Flemish Giant (FG) straightbreds. Doe genetic group and diet were important sources of variation (P less than .05) for all traits examined except for litter milk efficiency (litter gain/milk intake) and doe feed efficiency (milk yield/feed intake). The sire breed of litter effect did not influence (P greater than .05) lactational performance of does nor associative preweaning traits. Straightbred NN does were heavier at kindling, yielded more milk, reared a heavier litter by 21 d and were more efficient in converting feed into milk than were straightbred CC does (P less than .01). Significant heterosis was detected for milk production and for litter size and weight at 21 d. Reciprocal differences between crossbred doe groups were observed (P less than .05) for litter milk efficiency and doe feed intake. The 74% alfalfa diet was superior to the commercial control diet for effects on milk production and litter size and weight at 21 d, although doe feed intake was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1983

Breed, heterotic and diet effects on postweaning litter growth and mortality in rabbits.

The effects of sire breed, dam genetic group and diet on postweaning litter growth and mortality were evaluated in 208 litters of rabbits. Sire breeds were New Zealand White (NN), California (CC) and Flemish Giant (FG). Dam genetic groups were NN and CC straightbred and California X New Zealand White (CN) and New Zealand White X Californian (NC) reciprocal crossbreds. Litters were fed either a commercial diet or a 74% alfalfa diet. Litter size and weight at 56 d and litter gain (the difference between 56- and 28-d litter weights) tended to be lower in NN- compared with CC-sired litters; while feed intake was significantly lower and mortality was higher in progeny of NN sires. Litter 56-d weight, litter gain and litter feed efficiency (gain/feed intake) were improved (P less than .05) in litters sired by FG vs NN or CC bucks. Direct heterosis (CN and NC compared with NN and CC litters) for litter size, growth and feed-related traits was generally low (less than 11% in absolute value), while moderate heterosis levels (-21 and -22%) were observed for diarrhea-related and total mortality. Differences between NN and CC straightbred dams for litter size and weight at 56 d and litter gain were small, but in favor of NN dams. Diarrhea-related and total mortality were higher (P less than .05) in litters reared by NN vs CC straightbred dams.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗