Changes in Organ Weight, Sperm Quality and Testosterone Levels After Aluminum (Al) and Indium (In) Administration to Wistar Rats.

BACKGROUND: Aluminum and indium are widely used in industrial manufacturing, in pharmaceutical products, in medical treatments, and in food packaging, so they could reach organisms by different way. In order to clarify whether these elements are dangerous, we already demonstrated the ultrastructural modifications observed in the testicles, the epididymides, and the seminal vesicles of rat. Their pro-oxidative effect was also confirmed concomitantly to a decrease in anti-oxidant defenses in the blood, the testicles, and the liver. Thus, it seemed very logic to evaluate damages in the reproductive organs, especially on the exocrine and endocrine functions of the testicles. METHODS: Aluminum and indium were intraperitoneally administered to male Wistar rats. Sperm solution was obtained from cauda epididymides. Motility, viability, density, and malformation of spermatozoa solution were assessed. Serum total unconjugated testosterone concentrations were measured using RIA technique. RESULTS: Our results showed a decrease in weight of the testicles, epididymides, and seminal vesicles of indium-treated rats and an increase in the weight of their kidneys. A decrease in motility, viability, and density of epididymides stored sperm as well as generation of many spermatozoa malformations was also observed especially in indium-treated rats. Testosterone levels were increased in indium but were enhanced in aluminum group. This confirmed our previous studies showing that aluminum and indium are toxic for the testicular tissues. This could be explained by the generation of reactive oxygen species (ROS) affecting strongly the exocrine and the endocrine functions of the testicles. CONCLUSION: Aluminum and indium are disturbing elements for the exocrine and endocrine functions of rat testicles.

Histological and ultrastructural changes observed in testicles, epididymides, seminal vesicles and liver of rat after intraperitoneal administration of aluminum and indium.

BACKGROUND: Aluminum (Al) and indium (In) have been largely used in medicine, pharmacy, dentistry, manufacturing, engineering, clothing as well as food processing and packaging. Our previous study showed that In was accumulated as electron-dense materials in lysosomes of Sertoli and Leydig testicular cells and the liver ones, when administered to male rats as soluble form. For this reason, we have undertaken to confirm whether Al have the same behavior as In and to enlarge this behavior to other organs of the male reproductive system: epididymis and seminal vesicle. METHODS: Experiments were performed on 24 adult male Wistar rat weighing approximately 250 g. Animals were divided to 3 groups, received Al, In or saline solution as 7 chronic intraperitoneal injections over a period of two weeks and were sacrificed 24 h after the last injection. For ultrastructure study we used The Transmission Electron Microscopy (TEM). RESULTS: The TEM showed the presence of electron-dense granules in lysosomes of testicular cells (Sertoli and Leydig cells), and in the principal epididymal and seminal vesicle cells of Al and In treated rats. Impairments were observed in the endoplasmic reticulum and mitochondria and many vacuoles were identified in the cells cytoplasm. Our results concluded that lysosomes of Leydig and Sertoli cells, principal epididymis, and seminal vesicle cells as well as liver cells, played a central role in the extraction and concentration of Al and In under insoluble form after their introduction into the body as a soluble route. This mechanism intended to protect the organism against exogenous toxic and non-recognized mineral elements after their intrusion into the body. CONCLUSION: It looks important to proceed with the study of Al and In impact on the endocrine and exocrine functions of the male rat reproductive system.

Effects of the presence of indium on the mammary gland ultrastructure, body weight, food intake and plasmatic prolactin concentration.

Several studies have demonstrated the toxic effect of indium. This element induces impairments in many organs such as spleen, lungs and testicles after its systemic administration. Teratogenic and embryotoxic effects of this element have also been established. In the present study, we attempt to investigate the histological and the ultrastructural consequences of the presence of this element in mammary gland tissue using conventional transmission electron microscopy and to evaluate the incidences of its presence on the food intake, body weight and prolactin plasmatic concentration of lactating female rats. Our study showed that this element induced a significant decrease in food intake and body weight, and caused some cellular damage in the glandular epithelial cell such as cytoplasmic vacuolization and expansion of the ergastoplasm. The ultrastructural observations also showed many electron-dense surcharges in the lysosomes of the glandular epithelial cells. The electron probe microanalysis showed that these deposits are composed of indium and phosphorus. The lysosomes, known for their protective role of sequestrating foreign elements to avoid their diffusion in the blood, failed to stop the toxic effect of indium.

Comparison of the intracellular behavior of gold (Au) and indium (In) in testicle after their parenteral administration.

The subcellular behavior of several mineral elements was studied using modern techniques of observation like transmission electron microscopy and analysis like electron probe microanalysis and secondary ion mass spectrometry. In the present ultrastructural and analytical investigations, we undertake to compare the intracellular behavior of a heavy metal, gold, and a III-A group element, indium, on rat testicular tissues after their parenteral administrations. Our ultrastructural results showed that while gold was found only in the lysosomes of Leydig cells under electron dense needles, indium was observed as electron-dense deposits in the lysosomes of both Leydig and Sertoli cells. No ultrastructural modifications were observed in the testicular tissues of the control rats. The microanalytical study showed that gold was concentrated in lysosomes with sulfur as a sulfate crystalline structure whereas indium was concentrated in the same organelle as insoluble phosphate salt. These results demonstrated that testicular Leydig and Sertoli cells have the ability to selectively concentrate indium but gold was concentrated only in the first kind of cells. The mechanism implicated in this concentration phenomenon is a biochemical one involving intralysosomal hydrolytic enzymes, the acid phosphatase and the arylsulfatase. This mechanism occurs in order to protect the organism and to avoid the presence of toxic metals under soluble and free form.

Role of parietal and principal gastric mucosa cells in the phenomenon of concentration of aluminum and indium.

The subcellular behavior of aluminum and indium, used in medical and industrial fields, was studied in the gastric mucosa and the liver after their intragastric administration to rats, using, two of the most sensitive methods of observation and microanalysis, the transmission electron microscopy, and the secondary ion mass spectrometry. The ultrastructural study showed the presence of electron dense deposits, in the lysosomes of parietal and principal gastric mucosa cells but no loaded lysosomes were observed in the different studied hepatic territories. The microanalytical study allowed the identification of the chemical species present in those deposits as aluminum or indium isotopes and the cartography of their distribution. No modification was observed in control rats tissues. In comparison to previous studies describing the mechanism of aluminum concentration in the gastric mucosa and showing that this element was concentrated in the lysosomes of fundic and antral human gastric mucosa, our study provided additional informations about the types of cells involved in the phenomenon of concentration of aluminum and indium, which are the parietal and the principal cells of the gastric mucosa. Our study demonstrated that these cells have the ability to concentrate selectively aluminum and indium in their lysosomes, as a defensive reaction against intoxication by foreign elements.

Microscopy and microanalysis study of the indium (In) behavior in the intestinal mucosa, the liver, the kidney and the testicle.

Several studies have demonstrated that In used in medicine has several impacts on organs like spleen and lungs after its systemic administration. In the present study, ultrastructural and microanalytical methods were used to investigate the impact of the presence of this element in the intestinal mucosa, the liver, the kidney and the testicle after its administration in two ways. After intraperitoneal administration, In was selectively concentrated in the lysosomes of hepatocytes, of tubular proximal convoluted cells and of Sertoli and Leydig cells. After intragastric administration, ultrastructural study showed that this element was concentrated in the lysosomes of duodenal enterocytes. Microanalytical methods showed that In was precipitated in those organelles in the form of insoluble phosphate salts. Similarly to other studies, it seemed that since In is a foreign element for the organism, it was precipitated in lysosomes, very probably due to the activity of an intralysosomal enzyme the acid phosphatase, to avoid its invasion to organism via the blood. This mechanism of precipitation of the mineral elements is of great interest in the process of defensive reaction of the organism against intoxication by foreign elements.

[Role of the duodenal and hepatic cells lysosomes in the phenomenon of gadolinium accumulation]. / Rôle des lysosomes des cellules duodénales et hépatiques dans le phénomène d'accumulation du gadolinium.

The behaviour of the intestinal mucosa and of the liver after an administration of a gadolinium salt has been studied in the Wistar rat using transmission electron microscopy, ion mass spectrometry, and electron probe microanalysis. Six hours after parenteral administration, gadolinium is concentrated with phosphorus in the lysosomes of hepatocytes and Küppfer cells. Six hours after its oral administration, gadolinium is detected in the duodenal enterocytes lysosomes, but never in those of the liver cells. It is suggested that this mechanism of local concentration limits the diffusion through the digestive barrier of foreign elements, some of them being toxic and none of them having a physiological function.