ABSTRACT
Lithium salts are commonly used for treatment of bipolar disorder but prolonged treatment with therapeutic doses induces substantial toxic effects. In the present study we examined the effects of lithium carbonate on the ultrastructure of rat seminiferous tubules. Rats were exposed to lithium carbonate at doses of 35 mg/kg/day for 21 days. After lithium treatment, the tunica propria widened and folded together with convolutions of the basement membrane, myoid cells and lymphatic endothelium. In the seminiferous epithelium loss of germ cell attachment and appearance of expanded intercellular spaces between spermatogenic cells were observed. Early stages of spermatogenic cells showed nuclear protrusions or swellings because of an extensive enlargement of the outer nuclear membrane. Round spermatids exhibited abnormally shaped acrosomes and dilation of the subacrosomal space. Many abnormal, degenerated late spermatids with random orientation were seen towards the basal and adluminal compartments of the seminiferous epithelium. In addition, spermatids exhibited alteration in F-actin bundle ectoplasmic specialization and contained many mitochondria-associated granular bodies.
Subject(s)
Antimanic Agents/pharmacology , Lithium Carbonate/pharmacology , Seminiferous Tubules/drug effects , Seminiferous Tubules/ultrastructure , Spermatogenesis/drug effects , Animals , Antimanic Agents/toxicity , Lithium Carbonate/toxicity , Male , Mitochondria/drug effects , Mitochondria/ultrastructure , Rats , Rats, Wistar , Seminiferous Epithelium/drug effects , Seminiferous Epithelium/ultrastructure , Spermatids/drug effects , Spermatids/ultrastructureABSTRACT
In the adult brain, astrocytes account for about 40% of the cell population in the central nervous system. Normal, reactive and neoplastic astrocytes can be identified in immunohistochemical preparations by means of glial fibrillary acid proteins (GFAP) expression. This protein is considered to be a sensitive indicator of xenobiotics toxicity. Previous studies have demonstrated that 2 mM LiCl induce alterations of astrocyte morphology after 18-20 days of treatment in vitro. We have decided to study GFAP expression under such conditions. Immunodetection and Western blotting assays have shown 2 mM of LiCl to induce alterations of GFAP expression both after 12 days of treatment and after 18-20 days. Moreover, 2 mM of LiCl induce an alteration of the proteinic composition of cells.
Subject(s)
Antimanic Agents/pharmacology , Astrocytes/metabolism , Glial Fibrillary Acidic Protein/biosynthesis , Lithium Chloride/pharmacology , Animals , Astrocytes/chemistry , Astrocytes/cytology , Blotting, Western , Brain/cytology , Cells, Cultured , Electrophoresis, Polyacrylamide Gel , Glial Fibrillary Acidic Protein/analysis , In Vitro Techniques , RatsABSTRACT
Previously performed light microscopy studies have demonstrated Hep2 tumoral cells to be sensitive to concentrations of LiCl 1 mM and 2 mM. At those concentrations, LiCl induces morphological alterations consisting in cell hypertrophy, formations of cells with several nuclei similar to syncytium, cytoplasmic projections. This study focuses on the action of LiCl on growth kinetics, cloning capacity and protein composition of Hep2 tumoral cells. We have found LiCl (1 mM and 2 mM) to influence all those parameters.
Subject(s)
Lithium Chloride/pharmacology , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/pathology , Cell Division/drug effects , Clone Cells/drug effects , Electrophoresis, Polyacrylamide Gel , Humans , Kinetics , Proteins/metabolismABSTRACT
In order to study the influence of lithium on the cellular environment, we conducted research in multiple experimental models: groups of rats with normal cerebral excitability and groups susceptible to audiogenic convulsion, rat neuroglia cultures and perfusion of dog isolated head. We assumed blood composition to be a good indicator of cell environment composition. Blood serotonin level differs in the two groups of animals. Lithium induces a decrease of blood serotonin and an increase of amine concentration in some of the cerebral regions of rats susceptible to audiogenic convulsions. Inverse effects occur in rats with normal cerebral excitability. In the perfused, isolated head of a dog, lithium immediately decreases blood serotonin level. Na and water have a diminished metabolization during the first 24 hrs. in both animal groups. Decrease in metabolization is somewhat greater in hyperexcitable animals. Within 48 hrs. after lithium injection, there is an increase of Na metabolization, probably determined by its storage in the interstice. Renal elimination of K decreases under the influence of lithium 48 hrs. after administering one dose of lithium. Lithium induces, immediately after injection, a decrease of blood Na concentration in the efferent flow of the jugular vein of a perfused dog head. When used in cell cultures, lithium (2 mM concentration) stimulates glial cells division (astrocytes, oligodendrocytes), increases their growth and aging rates. The effects of lithium may be due to its toxicity. Therefore, lithium alters the composition of the cellular environment depending on dose and on the state of the body.
