[Autoradiographic study of the distribution of an anticholinesterase agent, 1-naphthyl-N-methyl[14C]carbamate, in the pregnant rat].
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Biomedical subjects
Publications and source records attributed to P Benard.
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Pregnant female rats and mice (18th day) received orally 10 mg/kg of 1-naphthyl-N-methyl-[14C]-carbamate (carbaryl), an anticholinesteratic drug. Animals were sacrificed 1, 5, 8, 24, 48, 72 and 960 h after administration and whole-body autoradiography was performed. Autoradiograms of the uterine cavity indicate a placental transfer and a foetal fixation of [14C] carbaryl metabolites. 14C-activity can be clearly seen in the foetus from the fifth hour; it persits till birth. We found 14C-activity in mice 60 h after birth. In both species there are some sites of accumulation in the foetal tissues, mainly in the eyes, central nervous system and liver.
In the horse, gamma-glutamyl transferase (GGT) was found to be mainly located in the kidneys, liver and pancreas. As renal lesions are followed by a urinary escape of enzyme, it can be assumed that if there are raised serum enzyme levels then the source will be chiefly from the liver and pancreas. In the blood, GGT can be measured either in plasma or serum. Its mean level in 58 horses was 12 U/L. This level was not affected by moderate dilution or slight haemolysis and its activity was only slightly decreased by storage at--30 degrees C. The relative hepatic specificity of this enzyme and its easy measurement make it a potentially very useful measure of liver dysfunction in the horse.
To test the hepatic specificity of gamma-glutamyl transferase in the cow, the tissue distribution of this enzyme was studied in 10 healthy adult cows. It was located mainly in kidney, pancreas, and liver. The relative hepatic specificity of this enzyme indicated that measurement of its activity in serum could be a valuable test of hepatic damage in the cow. The blood activity measured within 54 plasmas and 54 serums of apparently healthy animals was almost the same, 17.7 +/- 5.7 U/liter for plasma and 18.6 +/- 6.2 U/liter for serum.
In grey partridge, methoxy-ethyl-mercury is a potent reversible inhibitor of muscular creatine-kinase. This effect is probably the result of a fixation of mercury by the thiol groups of the enzyme molecule.
Gamma-glutamyl transferase distribution was studied in 10 pigs with an average weight of 100 kg. It was shown that kidney had the highest concentration of the enzyme, followed by pancreas, spleen and liver. Blood activities measured in plasma and sera from 54 animals were very similar, ie, 35+/-21 iu/litre for plasma and 36+/-14 iu/litre for serum.
Gamma-glutamyltransferase (GGT, EC 2.3.2.2) is in man and animals mainly a renal enzyme. It is also present in non-negligeable quantities in the liver except in certain rodents such as the rat. In the cells, the cytosoluble fraction of the enzyme is very low and most of the enzyme is linked to the microsomal fraction in vitro. This fraction permits its use in the diagnosis of liver and biliary disease by measurement of its serum activity and that of renal disease by measurement of its urinary activity. In biological research, the prospects offered by GGT both in human and animal cancers, and in pharmacology and toxicology makes it probably one of the most appreciated biological tests in the exploration of liver, biliary and renal function.
Metabolic study of 14C-19 Nortestosterone has been carried out in mice by macroscopic autoradiography and in calves by liquid scintillation counting. From the results, it is obvious that radioactivity is quickly eliminated mainly in urine and faeces. Ten weeks after administration, residual levels are very low.
The following parameters have been estimated in 15 red partridges (young adults of both sexes): 1. Biometry: relative weight of 10 organs (liver, kidneys, heart, brain, spleen, lungs, small gut, coecum, stomach, gizzard). 2. Hematology (mean +/- S.D.): Erythrocytes, 3.4 X 10(6) +/- 0.3 X 10(6) cells/mm3; packed cell volume 0.46 +/- 0.17; haemoglobin 103 +/- 27 g/l; mean red blood cell volume, 135.6 +/- 10.4 micrometer3; haemoglobin per red blood cell, 32.2 +/- 5,2 pg; haemoglobin concentration in red blood cells, 24.0 +/- 2.9 %; leukocytes, 36.9 X 10(3) +/- 7.8 X 10(3) cells/mm3; heterophilic, 32.3 +/- 8.3 %; basophilic, 5.3 +/- 1.5 %; eosinophilic, 1.4 +/- 1.5 %; lymphocytes, 56.1 +/- 7.3 %; monocytes, 4.6 +/- 1.4 %. 3. Blood biochemistry: Na +, 155 +/- 6 mEq/l; K +, 6.5 +/- 1.2 MEq/l; Cl--, 107 +/- 4 mEq/l; Pi, 53.3 +/- 14.4 mg/l; urea, 0.19 +/- 0.05 g/l; uric acid, 33.2 +/- mg/l; creatinin, 14.7 +/- 0.9 mg/l; glucose, 2.77 +/- 0.35 g/l; cholesterol, 1.38 +/- 0.36 g/l; total proteins, 44.1 +/- 5.9 g/l; albumin, 50.0 +/- 8.7 %; alpha globulins, 3.9 +/- 1.5 %; beta globulins, 7.5 +/- 2.2 %; gamma1 globulins, 31.5 +/- 5.6 %; gamma2 globulins 8.0 +/- 3.5 %. 4. Serum enzymology: Alkaline phosphatase, 8177 +/- 5078 u/l; SGOT, 356 +/- 138 u/l; SGTP 28.3 +/- 12.5 m/l; LDH, 955 +/- 570 m/l; GLD 12.6 +/- 12.4 u/l; CPD, 136 +/- 77 u/l; choline esterase, 2181 +/- 506 u/l. 5. Tissue enzymology: the 7 preceding enzymes have been estimated in 10 tissues listed in 1.
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Substituted benzamides have been the object of numerous metabolic studies including many by whole body autoradiography of rats and mice. The present study reports autoradiographic data concerning 14C-labelled Sulpiride in monkey. The Study was limited to the brain in order to elucidate the controversial question as to whether the drug can cross the blood-brain barrier. The results showed that in monkey, as in rat and mouse, there is no localization in the brain as can be clearly seen on the autoradiograms. In view of these results and of the undeniable neuroleptic properties of Sulpiride, an indirect mode of action through the release of endogenous mediators is proposed.
The study carried out on rats given orally the n-hexane lipido/sterolic extract of Serenoa repens (LSESR), supplemented with [14C]-labelled oleic or lauric acids or beta-sitosterol, demonstrated that radioactivity uptake in prostatic tissues shows the highest level in the case of administration of LSESR supplemented with [14C]-labelled oleic acid. This was clearly demonstrated on a rat with an induced fibro-muscular hyperplasia of the prostate and by quantitative measurements of radioactivity. Ratios of radioactivity in tissues compared to plasma show an uptake of radioactivity greater in prostate as compared to other genital organs, i.e. the seminal vesicles or to other organs such as liver.
Acetyl-DL-leucine [2-14C]: Tanganil a antivertigal drug has been injected intravenously in two macaca monkeys which have been sacrificed 2 and 5 minutes later. Radioactivity distribution has been studied by autoradiography in the brain. An important uptake of radioactivity is localized in the cortical structures and in several tisses such as nuclei of the vestibular system, including the inner ear.
Groups of 5 male and 4 female Cobs CD rats weighing 250--350 g were injected intraperitoneally, daily for 15 days, with 5 mumol HgCl2/kg, 5 mumol Na2SeO3/kg, or (5 mumol HgCl2 + 5 mumol Na2SeO3)/kg in a 10 ml/kg vol. of saline. Control animals were injected with saline only. Injection of saline or sodium selenite produced neither modification of diuresis, nor of urine elimination of sodium, potassium, chloride, phosphates, urea, creatinine and gamma-glutamyl transferase (GGT). Injection of mercuric chloride induced a massive increase of urine GGT, diuresis and phosphaturia and a decrease of kaliuria and natriuria. Those effects reflect a kidney tubular lesion which seems to be more severe in males than in females. Injection of mixed sodium selenite and mercuric chloride or separate injection of both compounds had similar effects. In both sexes, urine GGT elimination was delayed and about 2 times lower than with HgCl2 alone. In females, the other urine parameters were almost normal whereas in males, diuresis and phosphaturia were slightly increased and kaliuria decreased. The observation of urine GGT elimination attests, in vivo, that sodium selenite decreases tubular toxicity of mercuric chloride and resulting kidney function disturbances.
Quails fed methoxy-ethyl-mercury-treated wheat (20 ppm of Hg) during 10 or 20 days, have been submitted to a three-day fasting following contamination. The test proved to be lethal for a number of intoxicated animals but not for controls. Mercury clearance was modified by anorexia; following fasting, there was a redistribution of the metal, with high concentrations in the liver and kidneys. According to the results of a blood survey uric acid, urea and T. G. O. levels appeared to be the most altered parameters. Transient high blood uric acid levels in intoxicated and anorectic animals could be attributed to kidney dysfunctioning. A possible effect of methoxy-ethyl-mercury on neoglycogenesis was discussed.
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