PubMed Health⌕ Search

Biomedical subjects

P R Cheeke

Publications and source records attributed to P R Cheeke.

At least 55 records · Page 3Linked to original sources

Effects of synthetic and natural toxicants on livestock.

Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

Animals↗

Modifications of chronic hepatotoxicity of pyrrolizidine (Senecio) alkaloids by butylated hydroxyanisole and cysteine.

The chronic hepatotoxic effects of mixed pyrrolizidine alkaloids (PAs) from the poisonous plant tansy ragwort (Senecio jacobaea) and the ability of butylated hydroxyanisole (BHA) and cysteine to alter these hepatic effects were studied in male rats. In control animals, the i.p. administration of a single dose of mixed PAs, 160 mg/kg, produced marked fibrosis, biliary hyperplasia, megalocytosis, necrosis and calcification in liver 8 weeks post injection. In contrast, consumption of 0.75% BHA diet 10 days before and 14 days after PA administration reduced the incidence and/or completely prevented the occurrence of these pathological changes. Similar treatment with 1% cysteine, however, only reduced the severity of the hepatic lesions.

Animals↗

Consumption of poisonous plants (Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-metabolizing enzymes.

Effect of dietary tancy ragwort (Senecio jacobaea), comfrey (Symphytum officinale), bracken (Pteridium aquilinum) and alfalfa (Medicago sativa) on hepatic drug-metabolizing enzymes in rats were measured. Tansy ragwort and bracken increased (P less than 0.05) the activity of glutathione transferase and epoxide hydrolase. Comfrey and alfalfa increased (P less than 0.05) the activity of aminopyrine N-demethylase. Feeding bracken or St. John's wort (Hypericum perforatum) in conjunction with tansy ragwort did not influence chronic toxicity of tansy ragwort as assessed by rat survival time. Dietary tansy ragwort resulted in increased (P less than 0.05) hepatic copper levels; the other plants did not affect copper levels. The results do not suggest any major interaction in the toxicity of tansy ragwort with bracken or St. John's wort.

Animals↗

Effect of dietary Senecio jacobaea and injected Senecio alkaloids and monocrotaline on guinea pigs.

The chronic toxicity of 10% dietary Senecio jacobaea (SJ) in guinea pigs was studied during a 365-d feeding trial. The SJ plant contains hepatoxic pyrrolizidine alkaloids (PA). The chronic lethal dose (LD100) of SJ for guinea pigs was 1,264 g/kg initial body weight or 526% of initial body weight with an average survival time of 279 d. No mortality was observed in the controls. The LD100 and survival time were slightly, but not significantly, increased when 1% cysteine was included in the SJ diet. Histopathological examination of liver tissue from SJ-intoxicated guinea pigs revealed extensive megalocytosis, cytoplasmic and nuclear vacuolization, biliary hyperplasia and periportal fibrosis. Centrilobular areas appeared spared from necrotic lesions. The toxicity of acutely administered (ip) PA was determined in another experiment. The PA monocrotaline was nontoxic to guinea pigs at doses up to 1,000 mg/kg body weight, whereas jacobine and mixed SJPA were highly toxic at doses ranging from 100 to 150 mg/kg body weight. These results indicate that guinea pigs are resistant to dietary SJ and vary in response to single ip doses of isolated PA.

Animals↗

Absorption and excretion of pyrrolizidine (Senecio) alkaloids and their effects on mineral metabolism in rabbits.

A metabolism study was conducted with rabbits to determine the effect of consumption of 5% dietary Senecio jacobaea (SJ) on tissue mineral levels and mineral excretion. Gastro-intestinal (GIT) absorption of pyrrolizidine alkaloids (PA) from SJ was also studied by monitoring excretion into urine and feces and by the use of ligated gut segments in vitro. Inclusion of SJ into a diet containing added Cu (100 ug/g) and Zn (100 ug/g) caused a 2.6-fold increase in liver Cu concentration (P less than .05), decreased total liver Zn (P less than .05), and increased plasma Fe (P less than .05) when compared with rabbits consuming the same diet without SJ. Fecal and urinary excretion of Cu and Zn were not markedly affected by the addition of Cu, Zn and(or) SJ to rabbit diets. Excretion of PA from SJ in the diet was not affected (P greater than .05) by the addition of Cu and Zn to the diet. The PA elimination was much greater in urine than feces (P less than .001). Isolated PA from SJ were found to be readily transferred across the mucosa of isolated everted sacs of jejunum and ileum in vitro against a concentration gradient. These results suggest that the effects of dietary SJ on alterations in mineral metabolism are not due to changes in GIT mineral elimination. In addition, it appears that the resistance of rabbits to dietary SJ intoxication is not caused by low GIT absorption of PA, but rather by efficient urinary elimination.

Animals↗

Effect of feeding milk from goats fed tansy ragwort (Senecio jacobaea) to rats and calves.

Dried tansy ragwort, which contains pyrrolizidine alkaloids (PA), was fed to lactating dairy goats. Milk containing 7.5 ng of PA/g (dry weight basis) from these goats was fed to rats and calves. Rats fed a goats' milk diet for 180 days with a calculated total PA intake of 0.96 mg/rat had swollen hepatocytes of centrilobular distribution, and biliary hyperplasia, indicating PA involvement. Rats fed tansy ragwort at dietary levels of 1%, 0.1%, 0.01% and 0.001% (corresponding to PA intakes of 39.77, 5.04, 0.52, and 0.05 mg/rat) showed swollen hepatocytes, megalocytosis, biliary hyperplasia, and fibrosis. The histopathologic changes in the milk-fed rats and those given 0.001% tansy ragwort in the diet were similar. Definitive changes in 2 calves fed goats' milk were not detected. The results with rats indicate that PA are transferred in goats' milk and may produce hepatoxic effects.

Animals↗

Effect of consumption of milk from goats fed Senecio jacobaea on hepatic drug metabolizing enzyme activities in rats.

Milk from lactating goats fed tansy ragwort (Senecio jacobaea) was evaluated for its ability to influence hepatic drug metabolism. The milk after being freeze-dried was fed to male rats for 1 week ad lib. A significant reduction in the activities of hepatic aminopyrine N-demethylase and aryl hydrocarbon hydroxylase was obtained. There was no significant change in the activities of microsomal epoxide hydrolase and cytosolic glutathione S-transferase. The data suggest that consumption of milk from goats fed Senecio jacobaea produces a selective alteration of the activities of hepatic drug-metabolizing enzymes.

Animals↗

Comparative effects of the pyrrolizidine alkaloids jacobine and monocrotaline on hepatic drug metabolising enzymes in the rat.

The effect of i.p. administration of the pyrrolizidine alkaloids jabodine and monocrotaline on the activities of hepatic epoxide hydroase, glutathione S-transferase, aminopyrine N-demethylase and aryl hydrocarbon hydroxylase (AHH) was investigated in young, male Long-Evans rats. Jacobine significantly increased the activities of epoxide hydrase and glutathione S-transferase but caused a reduction of cytochrome P-450 content and in related monooxygenase activities. In contrast, monocrotaline failed to stimulate epoxide hydrase while diminishing the activity of glutathione S-transferase, aminopyrine demethylase and AHH. There was no effect of jacobine or monocrotaline in vitro on the hepatic drug metabolizing enezymes studied except for a slight stimulation of epoxide hydrase activity by jacobine and monocrotaline and a small reduction of aminopyrine demethylase activity by monocrotaline. These results demonstrate that pyrrolizidine alkaloids can have a differential effect on hepatic enzymes depending on the type of alkaloid and the enzyme studied.

Animals↗

Comparative effects of alfalfa saponins and alfalfa fiber on cholesterol absorption in rats.

Intestinal absorption of cholesterol was measured in control rats fed semipurified diets and in rats fed alfalfa meal, in which saponins had been previously extracted, or this extracted material plus alfalfa saponins. A dose of 2 mg radioactive cholesterol was administered intragastrically, and fecal excretion of labeled neutral steroids measured. Absorption of cholesterol was about 76% in control animals, and about 47% in alfalfa-red rats. Extraction of saponins from alfalfa eliminated the cholesterol absorption-lowering effect, while addition of 0.26% alfalfa saponins to the extracted alfalfa restored its activity. The results demonstrate that alfalfa saponins are responsible for the effect of alfalfa meal in reducing cholesterol absorption, and that alfalfa fiber is not involved in this activity.

Animals↗

Enterotoxemia in rabbits.

The presence of Clostridium perfringens Type E iota toxin was confirmed from the cecal contents of 23 of 46 rabbits which died of enteritis complex. The most consistent lesions observed were hemorrhage and edema in the cecum. Rabbit toxicity tests showed the toxic cecal contents were lethal for young rabbits unless incubated with Clostridium perfringens Type E antiserum.

Animals↗