R. Derache

Effect of the insecticidal carbamate derivatives (carbofuran, pirimicarb, aldicarb) on the activity of acetylcholinesterase in tissues from pregnant rats and fetuses

Abstract Groups of Sprague-Dawley female rats (eight animals per group) were given: 0.001, 0.01, or 0.1 mg/kg of aldicarb; 0.05, 0.25, or 2.5 mg/kg of carbofuran, or 2 or 20 mg/kg of pirimicarb by gastric intubation on the 18th day of gestation. All are carbamate derivatives with insecticide properties and are used in phytopharmacy. The rats were killed 1, 5, and 24 hr after feeding. The activity of acetylcholinesterase (AchE) in blood, brain, and liver from dams and fetuses was determined by a kinetic method. Signs of central and peripheral effects due to inhibition of AchE occurred 5 min after the dams were treated. All three carbamates caused a significant decrease in the activity of AchE in most maternal and fetal tissue samples examined 1 hr after treatment. The effect lasted 24 hr after doses as small 0.01 and 0.1 mg/kg aldicarb were administered. The decrease in the activity of AchE was generally more prominent in fetuses than in dams.

Foetal and maternal rat brain acetylcholinesterase: isoenzymes changes following insecticidal carbamate derivatives poisoning.

Pregnant rats (18th day) were orally given insecticidal carbamates with anticholinesterasic properties: 50 mg/kg carbaryl, 0.1 mg/kg aldicarb, 2.5. mg/kg carbofuran and 20 mg/kg pirimicarb. The acetylcholinesterase (AChE) isoenzymes from the brain of mothers and their foetuses were separated by electrophoresis on polyacrylamide gel. The four carbamate derivatives caused a significant lowering of the percentage of the least mobile isoenzyme (isoenzyme 1) in mother. Aldicarb, carbaryl and pirimicarb also caused a significant decrease in the percentage of the first foetal isoenzyme. The second foetal isoenzyme underwent a decrease after treatment with aldicarb or carbofuran.The distribution of the foetal isoenzymes was seen to be different to that of the dams in both control and treated animals. The difference in sensitivity of the cerebral AChE to the insecticides under investigation is thought to depend on differences of the fixation of carbamate derivatives on the foetal and maternal isoenzymes.

Etude nutritionnelle et toxicologique, chez le rat, d'un contaminant alimentaire: L'etain

Nutritional and toxicological study of rats fed a diet containing tin A toxicological, nutritional and histological study of rats on a diet containing 0.5 g of tin (Sn Cl2) per 100 g of dry food for one month has been made. By γ radioactivity measurements (with 113Sn used as a tracer) it is shown that this metal does not practically clear the digestive barrier. Otherwise the classical coefficients of nitrogen nutrition and the urinary parameters (volume, glucose, pH) are not influenced; but the growth of treated animals is obviously slower than control animals because of their reduced ingestion of food. Moreover after one month of treatment a marked anaemia results since the hematocrit and hemoglobin levels are perceptibly reduced. Lastly the histological investigations give evidence of notable irratation of the total gastrointestinal tract. This study, as that of many authors, raises the question of present permissible levels of tin (up to 250 ppm) in foods.

Effect of various dietary components on absorption and tissue distribution of orally administered inorganic tin in rats

Summary The absorption of tin from the gastro-intestinal tract and its distribution in the tissues was studied in groups of rats given 113 Sn-labelled stannous chloride by gastric intubation together with various other food components, namely sucrose, ascorbic acid and potassium nitrate, given with the tin salt either separately or all together, ethanol (given as a 20% solution), a solution of albumin and an emulsion of sunflower oil and 1% Tween 20. In all groups, 90–99% of the administered radioactivity was excreted in the faeces within 48 hr, at which time faecal excretion and retention in the alimentary tract accounted for 98·7–99·9% of the dose. Only traces of 113 Sn were detected in the wide range of organs and tissues examined, irrespective of the other food components administered with the tin salt.

Effet de I’acide tannique sur la sécrétion gastrique chez le rat

We have studied the effect of tannic acid on gastric secretion in the stomach of the rat [Shay et al., 1945]. Using both single and repeated dosages, our findings disclose: The administration of a sin

Inhibition of two rat hepatic microsomal drug-metabolizing enzymes by a carcinogenic N-nitrosated pesticide: N-nitrosocarbaryl

N-Nitrosocarbaryl (N-methyl-1-naphthyl N-nitrosocarbamate) was intraperitoneally administered to male and female rats on four consecutive days at the following doses: 6.25 mg, 12.5 mg, 25 mg and 50 mg/kg body weight/day in olive oil solution; the controls received just the oil. In a second experiment, a daily intraperitoneal dose of 25 mg/kg of N-nitrosocarbaryl was given for 1, 2, 3 or 4 days; the animals were killed 24 h after the last treatment. The two following microsomal enzymatic activities were assayed: aniline aromatic hydroxylase and p-nitroanisole O-demethylase; the levels of cytochrome P-450, proteins and RNA were measured in the hepatic microsomal fraction. N-Nitrosocarbaryl is an inhibitor of the two investigated microsomal monooxygenases at doses of 25 and 50 mg/kg when administered on 4 consecutive days. During the daily administration, enzyme inhibition is seen in females after one day of treatment whereas cytochrome P-450 only becomes lowered after 4 days of administration. In males, no modification of this parameter is observed whereas the activities of microsomal monooxygenases are inhibited. These results suggest that N-nitrosocarbaryl could act on the active sites of the enzymes which metabolize aniline and p-nitroanisole.

Effect of nitrites and nitrates on irrigation and secretion of gastric mucosa in rat.

SummaryAn aspect of the vasomotor effect of nitrites and nitrates was studied by investigating the influence of these substances on the mucosal blood flow and hence on gastric secretion in the rat. Firstly, point measurements were obtained using an aminopyrine clearance technique after intravenous nitrite and nitrate treatment. Then with an appreciably different technique (14C-aniline clearance on perfused stomach) the kinetics of the phenomenon were followed after, firstly, intravenous administration of the two agents and secondly their intragastric administration. It is interesting to note that nitrites and nitrates are active to differing degrees and present opposing effects: nitrites decrease whereas nitrates globally enhance the factors under consideration (gastric mucosal blood flow, gastric juice volume, acid and pepsin output). The strong action of nitrites, even though retarded, persists throughout intragastric perfusion. However, intravenously administered, nitrates have a more transitory effect and cause no modification on intragastric administration. The flow rate-gastric parameter correlations are significant in all cases and show modifications of the aqueous compartments of the body.

Absorption gastro-intestinale, chez le rat, de l'anisole, du trans-anéthole, du butylhydroxyanisole et du safrole

A method of in situ perfusion in the rat was used to study the gastro-intestinal absorption of four food additives derived from methoxybenzene, namely anisole, trans-anethole, butylated hydroxyanisole and safrole. These compounds are largely absorbed from the digestive tract by a mechanism of passive diffusion, but the absorption kinetics vary from one product to another. These variations are explained, at least partially, by differences in the coefficients of liposolubility.

Activité enzymatique, au niveau des microsomes hépatiques du rat, après ingestions d'acide oléique, d'acide érucique et de leurs dérivés

Abstract Female rats were given oleic acid, erucic acid, ethyl oleate, ethyl erucate, triolein and trierucin by oral intubation for 4 days (3 g/kg/day) and drug-metabolizing enzymes were investigated. A significant increase in liver microsomal enzymes occured after erucic acid treatment. Ethyl erucate and triolen exerted a stimulatory effect only on certain enzymes whereas oleic acid, ethyl oleate and trierucin had no effect. These changes were associated with significant modifications in DNA, RNA and protein content of the rat liver and of the hepatic fraction containing microsomes. The data indicated that erucic acid acted as a potent inducer of microsomal enzymes and suggested that this acid was a “foreign” compound.

Dietary effects on inhibition of rat hepatic microsomal drug-metabolizing enzymes by a pesticide (Morestan®)

Female rats were fed for 21 days on 5 semi-synthetic diets containing 8 or 30% proteins, 1 or 25% lipids respectively, the control animals being given a diet containing 20% proteins and 5% lipids. The animals on each diet were then subdivided into two subgroups and on the 22nd, 23rd, 24th and 25th days were given an oral dose of 75 mg/kg of Morestan in solution in peanut oil (PO) or a dose of oil only. The microsomes were prepared 24 h after the last administration and aniline aromatic hydroxylase, aminopyrine and N-methylaniline N-demethylase activities and cytochrome P-450, protein and RNA levels were measured. Whatever the diet, Morestan inhibited N-demethylase activities and decreased the cytochrome P-450 level; liver protein and RNA levels and microsomal RNA level increased. The 25% lipid diet alone increased activity of the three enzymes studied, without modifying the cytochrome P-450 level; Morestan produced antagonism of this effect in the rats on this diet. The decreased cytochrome P-450 level caused by Morestan was higher in animals on the 8% protein diet.