Biochemical changes and morphological alterations of liver and kidney in hamsters after administration of the HMG-coenzyme A reductase inhibitor, simvastatin: prevention and reversibility by mevalonate.

The present study analyses the effects of simvastatin, a specific inhibitor of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase) in male Syrian hamsters fed a standard diet or a diet supplemented with 0.12% cholesterol and 20% coconut oil. In hamsters fed the standard diet, gastric administration of simvastatin (10 mg/kg/day) during 12 days was found to be lethal and to have hepatotoxic and nephrotoxic effects. This toxicity was exacerbated in hamsters fed a hyperlipidaemic diet and was preceded by a progressive anorexia and loss of body weight. Marked elevations in serum aspartate and alanine aminotransferase activities were associated with the organ lesions. All elevated biochemical changes and morphological alterations were prevented or reversed by coadministration of mevalonate, the product of the HMG-CoA reductase. It is suggested that the dramatic effect of simvastatin could result from depletion of a non-sterol metabolite of mevalonate in spite of a lack of protective effects of farnesol and geranylgeraniol in the following study. The toxicity of simvastatin could indeed result from the low basal activity of HMG-CoA reductase in hamster liver coupled with a prolonged inhibition of mevalonate synthesis.

Quantitative histology of the rat thyroid. Influence of histologic techniques on the morphometric data.

The influence of various histologic techniques on the results obtained by morphometric analysis of the rat thyroid gland was studied. The limits of thyroid follicles were more clearly defined in both silver-impregnated paraffin-embedded sections and resin-embedded semithin sections than in routinely stained paraffin-embedded sections, thus enabling more accurate measurements of thyroid structures. Due to its simplicity, the silver impregnation method is clearly useful for histomorphometric studies when large numbers of measurements are involved. C cells were easily identified in paraffin-embedded sections by immunohistochemical staining. The measurement of interstitial tissue in sections without immunostaining of C cells led to an overestimation of the volume fraction of interstitial tissue.

[Histomorphometric study of the morphological variations of the thyroid follicles in the rat as a function of age and sex]. / Etude histomorphométrique des variations morphologiques du follicule thyroïdien chez le rat en fonction de l'âge et du sexe.

The thyroid glands of male and female rats (Sprague Dawley) 10 to 60 weeks of age were examined histomorphometrically. The results show a clear sex dimorphism. The thyroid follicles in the male animals show a greater functional activity than in the female animals. But while the morphology of the follicles in the females was constant throughout the period of observation, in the males the activity gradually diminished.

Critical analysis of the histomorphometry of rat thyroid after treatment with thyroxin and propylthiouracil.

The morphological variations of rat thyroid follicles after treatment with either thyroxin or propylthiouracil were evaluated by histomorphometry. A silver impregnation technique allowed a precise visualization of thyroid follicles on histological sections. The histomorphometric values (cell height, follicular diameter, percentage of epithelial cells) were obtained using a semi-automatic image analyser. The statistical tests used were analysis of variance (Fisher's test) and the Newman-Keuls tests. The results obtained showed that thyroxin treatment did not lead to any modification in histomorphometric values. Propylthiouracil, on the contrary, caused profound alterations in the morphology of thyroid follicles and in particular an increase in the height of the follicular epithelium. These changes were induced by a deficiency in thyroid hormones leading to an increase in thyroid-stimulating hormone (TSH) release. This study shows that with rigorous methodology, histomorphometry is adaptable to the requirements of a simple and reproducible evaluation of substances capable of causing functional perturbations and their effects on the thyroid gland.

Quantitative evaluation by immunocytochemistry of the age-related variations in thyroid C cells in the rat.

C cells in the rat thyroid were identified easily and clearly using an immunocytochemical technique. This identification allowed a precise study to be carried out on the quantitative variations of these cells with respect to age (between 10 and 60 weeks) and sex of the animals. No difference related to sex was seen. There was a net increase in the volume fraction of C cells (hyperplasia) with age.

The urethral muscle (musculus urethralis) of the female calf. Anatomical, histological, histochemical and morphometrical data.

Parts of the female urethra were examined topographically and microscopically in the female calf. The thickness and the straight course of the fibres of the musculus urethralis could best be analyzed in the ventromedian region of the urethra. Examination of the surface area and the distribution of the two primary metabolic fibre types showed that the urethral muscle is capable of contracting quickly with predominantly anaerobic metabolism. The different relationships between type I and type II fibres could be determined also in relation to the position of the lamina propria mucosae.

[Effects of 2 anabolizing substances with estrogenic action on the urethral muscle of the calf. Histochemical and morphometric study]. / Effets de deux substances anabolisantes à action oestrogénique sur le muscle urétral du veau. Etude histochimique et morphométrique.

The testing of anabolizer utilization in cattle farming needs quick, sure and cheap detection techniques. The administration of oestrogen to cattle produces hypertrophy of the prostate, bulbourethral glands and urethral muscle. The aim of this study was to quantify the effect of the association of zeranol (an hormonomimetic drug acting as an oestrogen) and trembolone (a steroidic structure originating from testosterone) on the urethral muscle of bull calves which is easy to sample in the slaughter-house. An histoenzymological and morphometric study of the urethral muscle of 90 bull calves that had been treated showed considerable hypertrophy in transversal sections of the muscle fibers that was increased by more than 90% in the two main types of striated muscle fiber. The morphological method used is proposed for monitoring the meat of untreated bull calves, requested by a class of consumers.

Secretory glycoproteins of major vestibular glands (Bartholin's glands) in female calves. Studies with usual histochemical methods and with lectin-horseradish peroxidase conjugates in normal animals and in animals implanted with anabolic drugs.

The nature of mucins synthetized by the major vestibular glands of normal female calves and animals treated by anabolic drugs was investigated by usual histochemical methods and by lectin conjugate methods: Canavalia ensiformis (Con A), Limulus polyphemus (LPA), Lotus tetragonolobus (LTA), Arachis hypogaea (PNA), Ricinus communis (RCA I), Glycine max (SBA) and Triticum vulgaris (WGA). Two main secretory cell types, i.e. acinar and tubular cells, could be distinguished. The former produced sialomucins, whereas the latter produced neutral mucins. WGA and PNA showed strong binding to all secretory cells while LTA, RCA I and SBA exhibited a weaker affinity. Treatment with anabolic drugs enhanced O-acetyl sialic acid synthesis and we noted de novo synthesis of sulfomucins. However, the staining intensity of LTA was stronger than in control calves. Tubular secretory cells of treated animals revealed an intense secretion of neutral mucins but, in contrast, all tested lectins were less intensively bound. The present study provides additional histochemical information on Bartholin's glands. A shortened procedure is proposed to detect animals treated with anabolic drugs when morphological changes are lacking.

Toxicological studies of deltamethrin.

Deltamethrin [( S]-alpha-cyano-3-phenoxybenzyl-cis-(1R,3R)-3-(2,2-dibromovinyl+ ++) (2,2-dimethyl-cyclopropane-carboxylate], is the most potent insecticide known at the present time. But it is also one of the most toxic pyrethroids for vertebrates. The toxicity study of deltamethrin was performed on mice and rats, and on anaesthetized dogs, the administration route being either oral or intravenous. The oral LD50 of deltamethrin suspended in 10% gum-arabic solution was 5.54 +/- 1.29 g/kg p.o. in male mice and 3.45 +/- 1.27 g/kg p.o. in female mice. In rats and anaesthetized dogs, deltamethrin at high concentrations by the oral route engendered neither mortality nor signs of intoxication. When dissolved in glycerol formal and given intravenously, the LD50 of deltamethrin was as low as 3.44 +/- 0.67 mg/kg in anaesthetized dogs. Values obtained for the toxicity of deltamethrin varied not only with the animal species and sex involved, but also with the administration routes and solvents used. Administered orally, it was 100 times less toxic when suspended in gum-arabic solution than dissolved in oil or organic solvent. Whatever the animal species, sex, administration routes and solvents employed, the poisoning symptoms of deltamethrin are identical, i.e. salivation, ataxia and choreoathetotic movements with rolling convulsions, appearing within 7 h after administration. No cellular alteration was detectable by means of optical microscopy of excised organs.