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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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Gold, a heavy yellow-colored metal, is usually found in nature as a metallic element or as salts. This noble metal historically had a reputation as an anti-inflammatory medicine for rheumatoid arthritis, a nervine, and a remedy for nervous disorders, as well as a potential anticancer agent. It has also been used as component in dental restorations and in implant materials. The present study was undertaken to point out histological and ultrastructural effects of gold, administered by intraperitoneal route, in pregnant female reproductive organs (ovary and uterus), in order to clarify its side effects on the reproductive function. Using the transmission electron microscopy (TEM), the ultrastructural investigations of both ultrathin ovarian and uterine sections of treated pregnant rats revealed the existence of numerous heterogeneous clusters with very electron-dense inclusions characterized by various aspects in the lysosomes of granulosa, theca interna cells, and theca externa cells. Degeneration of these tissues, like cell vacuolization, marked expansion of the endoplasmic reticulum, mitochondrial alterations, and necrotic foci, were also highlighted. Moreover, huge phagolysosomes and high numbers of eosinophils as signs of inflammation were also identified especially in endometrial and myometrial cells of gold-treated rats. The ultrastructural investigations of reproductive organ sections of control pregnant rats showed a normal ultrastructural aspect and no loaded lysosomes. These results speculated the toxicity of gold at the used dose. The observed signs of toxicity allowed concluding that the important role of lysosome in the sequestration of this element under an insoluble form in all categories of cells in the studied tissues does not seem to be efficient.

Rare earths have been widely used in a huge number of areas in industry and medicine. Therefore, they exist in the environment and possibly accumulated within the human body. However their effects in the living organism particularly in the female reproductive system are still unclear. In this work, the subcellular behavior of lanthanum and cerium was investigated through the Transmission Electron Microscopy (TEM), in different territories of the reproductive system of Wistar rats exposed intraperitoneally to soluble solution of these elements during 2 weeks. Ultrastructural investigations of ultrathin sections from uterus and ovary of treated rats revealed the existence of inclusions with high electron density and heterogeneous aspects in the lysosomes of uterus and ovary cells. Many disruptions of architecture were observed, accompanied with several changes like vacuolations, significant expansion of the endoplasmic reticulum, mitochondrial alterations and necrotic cells, demonstrating the toxicity of these elements with doses used. Phagolysosomes as well as eosinophils were also seen. Our experimental investigations revealed no intralysosomal inclusions in ultrathin sections of the uterus and ovary of pregnant control females. The original mechanism implicated in this insolubilization-concentration phenomenon of these elements, as non-soluble phosphate form, in the lysosomes is a biochemical one involving intralysosomal hydrolytic enzymes, the acid phosphatase., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

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., (© The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip 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.

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., (Copyright © 2011 Wiley Periodicals, Inc.)

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.

Aluminium and indium are two elements used in industrial and medical fields. The purpose of this work was to study the subcellular localization of these elements, after their single and simultaneous oral administration to rats. 2h after the administration of these two elements, the small intestine and the liver were removed.Ultrastructural study showed the presence of electron dense deposits in the lysosomes of apical parts of duodenal enterocytes. When the minerals were administered simultaneously, deposits were observed in lysosomes of duodenal and jejunal enterocytes. No deposits were seen in the hepatic tissue of treated and control rats. Microanalysis identification showed that the deposits are constituted of aluminium, indium as well as phosphorus. Our results suggested that the elements are concentrated, in lysosomes, under the form of insoluble phosphate salts and it seemed that there are no specific lysosomes for the concentration of minerals since the two elements were concentrated in the same lysosome when they are administered simultaneously.

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.

Intragastric administration to rats of four soluble lanthanides cerium, lanthanum, europium, thulium and of three soluble elements of group IIIA aluminium, indium and gallium has been shown in previous studies. In this work two new rare earths gadolinium and terbium were studied using the same protocols and the same methods (transmission electron microscopy and ion microanalysis). among the previously studied elements, some of them were administered simultaneously on the one hand aluminium and indium, and on the other hand, lanthanum and cerium. These metals were looked for in intestinal mucosa, liver and kidney. The results showed: a) gadolinium and terbium were selectively concentrated in lysosomes of duodenal enterocytes, precipitated as non-soluble phosphate salts and eliminated with the cell's turn-over in less than 48 hr; b) Administered simultaneously, they precipitated in the same lysosome. c/ none of them was observed in the liver or kidney even with high dose. This study brings up to nine the number of elements forming a non-soluble phosphate salts, explaining their precipitation in lysosomes. None of them have a physiological role, two are toxic (aluminium and indium). This rapid intralysosomal concentration is an efficient mechanism which limits the diffusion of the foreign substances through the digestive barrier, then permits their elimination along with the cytoptose phenomenon in the intestinal lumen.

The subcellular localization of cerium and lanthanum in the intestinal mucosa was studied after oral administration of cerium chloride or lanthanum chloride or lanthanum chloride followed 30 minutes after of cerium chloride to young adults Wistar rats. Two methods of observation and microanalysis were used. The transmission electron microscopy revealed the presence of dense electron granulations in the lysosmes of the duodenum enterocyte, when these elements were administrated simultaneously. The ion mass microanalysis permits to detect the presence of La and Ce as bright points outlining the intestinal villi. These points correspond to the lysosomes containing the granulations previously described. These granulations are formed by the cerium and the lanthanum associated to the phosphor and forming probably insoluble salts of Ce/La phosphate.

The behavior in the intestinal barrier of nine elements (three of the group III-A, four lanthanides and two actinides), absorbed as soluble salts, has been studied by two microanalytical methods: electron probe X-ray micro analysis (EPMA) and secondary ion mass spectrometry (SIMS). It has been shown that the three elements of group III-A, aluminium, gallium and indium; and the four lanthanides, lanthanum, cerium, europium and thulium, are selectively concentrated and precipitated as non-soluble form in enterocytes of proximal part of the intestinal tract. SIMS microscopy has shown that these elements are concentrated as a number of submicroscopic precipitates, most of them localized in the apical part of the duodenum enterocytes, where they are observed from one hour to 48 hr after a single intragastric administration. No precipitate is observed after three days. It is suggested that this mechanism of local concentration limits the diffusion of these elements through the digestive barrier, some of them being toxic and none of them having a recognized physiological role. Additionally, the precipitation in duodenal enterocytes, the life time of which is on the order of 2-3 days, allows the elements absorbed as soluble form to be eliminated as a non-soluble form in the digestive lumen along with the desquamation of the apoptotic enterocytes. The intracytoplasmic localization of the precipitates are supposed to be the lysosomes although no direct evidence could be given here due to the very small sizes of the lysosomes of enterocytes. The same results were not observed with the two studied actinides. After administration of thorium, only some very sparse microprecipitates could be observed in intestinal mucosa and, after administration of uranium, no precipitates were observed with the exception of some in the conjunctive part of the duodenal villi.

Unlabelled: The composition of the World Health Organisation (WHO) solution in oral rehydration therapy has remained controversial because of its total osmolarity (303 mosm/L) and higher sodium concentration (90 mEq/L), increasing the risk of hypernatraemia., Aim of the Study: To compare the efficacy of two reduced-osmolarity oral rehydration solutions (S1: 268 mosm/L and 50 mEq/L Na(+); S2: 240 mosm/L and 60 mEq/L Na(+) ) with the WHO recommended formula taken as the reference solution. Water, electrolytes and glucose fluxes were directly measured in vivo, in isolated ligated loops of rat jejunum (n=12). Intestinal secretion was induced by exposing jejunum to cholera toxin (CT=20 microg/loop)., Results: All three test solutions similarly reversed cholera toxin-induced net water absorption (3.37 +/- 1.35; 3.31 +/- 0.43 and 3.13 +/- 0.66 microL/min.cm(2) for S1, S2 and WHO solutions respectively). However, net Na secretion induced by cholera toxin was observed with S1 and S2 while Na absorption occurred with the WHO solution., Conclusion: For a same amount of water absorbed, Na absorption from reduced - osmolarity rehydration solutions is lower than with the WHO solution. Our data may contribute to a better rationale for the use of orally administered hydration solutions in man.