Thymus Of Male Rats Research Articles

Effect of gliprolines on lipid peroxidation rate in male rats’ immunocompetent organs under conditions of information stress

Introduction. The study of various aspects of the stress-reactivity of the body’s immune system, along with the search for correction tools characterized by immunoregulatory properties, is one of the most relevant areas of physiology and pharmacology. Currently, neuropeptides belonging to the group of glурrоlins (the registered drug “sеlаnk” and the new compounds Рro-Glу-Рro-Leu and Рro-Glу-Рro) are of particular interest in practical application as promising bioregulators, in particular their effects on the processes of free radical oxidation, as well as the ability to restore changes from the immune system, including those formed in response to stress.The aim of the study: was to study the effect of glурrоlins on the intensity of lipid peroxidation, catalase activity in the spleen and thymus of male rats under experimental information stress.Material and methods. The study was performed on white nonlinear male rats on which the model of information stress, based on the formation of behavior in animals in a multi-alternative food-producing maze, was reproduced for 20 days. The initial content of malondialdehyde, the rate of spontaneous and ascorbate-dependent lipid peroxidation were determined by standard spectrophotometric methods, and the activity of catalase in the homogenate of the thymus and spleen of experimental animals was evaluated.Results. Under the studied stress conditions, an increase in peroxidation processes was noted. Against the background of the introduction of sеlаnk, Рro-Glу-Рro and Рro-Glу-Рro-Leu, the suppression of the intensity of lipid peroxidation processes in the homogenates of the spleen and thymus tissue of male rats was established (a decrease in the initial level, the rate of spontaneous and ascorbate-dependent lipid peroxidation).Conclusions. Injection of neuropeptides belonging to the group of glyprolins (sеlаnk, Рro-Glу-Рro-Leu and Рro-Glу-Рro) under informational stress conditions contributes to the suppression of the intensity of lipid peroxidation processes, which indicates the stress-protective and immunocorrective effect of the studied substances.

Gonadotropin-releasing hormone stimulation of annexin A5 expression in the thymus of male rats.

As gonadotropin-releasing hormone (GnRH) is expressed in the thymus, its direct action on thymic cells, including thymic involution, has been suggested. Annexin A5 (ANXA5), a biomarker of GnRH, was used to determine whether GnRH affects the thymus of male rats. Immunohistochemistry showed positive reactions for ANXA5 in large medullary epithelial cells at 30 days of age, and the expression continued until 180 days of age. Organ culture of thymus pieces was performed to examine the direct action of a GnRH agonist (GnRHa) on the expression of Anxa5 and Gnrh mRNA. Thymus tissues obtained from male rats (40–60 days old) were cut into small pieces (2–3 mm3) and incubated for 3 hr with the GnRHa. The expression levels of Anxa5 and Gnrh mRNA were augmented by the GnRHa. Immunohistochemistry of these tissue fragments showed that ANXA5 expression was enhanced, especially in medullary epithelial cells. These results revealed that GnRH synthesis in the thymus could affect thymic epithelial cells after puberty.

ULTRAMICROSCOPIC CHANGES OF RATS PARATHYROID GLANDS AND THYMUS AFTER SINGLE ADMINISTRATION OF CYCLOPHOSPHAMIDE AT THE DIFFERENT PERIODS OF OBSERVATION

Introduction: Cyclophosphamide has wide spectrum usage as first-line drug in cancer chemotherapy that is why a detailed study of its effect on individual cell populations is of great interest for science and practice. The interaction of the nervous, immune and endocrine systems plays essential role in the homeostasis maintaining. The aim: This study aimed to investigate the ultramicroscopic changes that occur in the parathyroid glands and thymus of male rats after cyclophosphamide administration. Materials and methods: Twenty-four WAG matured male rats were divided randomly into two groups. The first group served as control and was provided 0.9% soluble sodium chloride. The second group received cyclophosphamide in a dosage 200 mg/kg of body weight of animal by intramuscular single injection. All animals were sacrificed on the 7th and 30th day after injection. Parathyroid gland and thymus specimens were dissected out and processed for electron microscopy. Results: The results showed that cyclophosphamide exposure caused marked ultramicroscopic changes in rats parathyroid glands and thymus. On the 7th day after immunosuppression, the nuclei of parathyrocytes have deep wavy invaginations, amount of the organelles that participate in the protein synthesis is reduced to a minimum in the cytoplasm of the chief cells. Characteristic feature is the appearance of numerous plasma cells and active macrophages in thymus. There is a tendency to normalization of the parathyroid structure on the 30th day after administration of cyclophosphamide and reduction of mitotic activity of lymphocytes in thymus, which points to the development of involution process. Conclusions: This data can be successfully extrapolated from experimental animals to humans.

A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.

Reduced fetal nutrition and rapid postnatal growth accelerates the aging phenotype in many organ systems; however, effects on the immune system are unclear. We addressed this by studying the thymus from a rat model of developmental programming. The recuperated group was generated by in utero protein restriction, followed by cross-fostering to control-fed mothers, and were then compared with controls. Fat infiltration and adipocyte size increased with age (P < 0.001) and in recuperated thymi (P < 0.05). Cortex/medulla ratio decreased with age (P < 0.001) and decreased (P < 0.05) in 12-mo recuperated thymi. Age-associated decreases in thymic–epithelial cell (P < 0.01) and thymocyte markers (P < 0.01) were observed in both groups and was decreased (P < 0.05) in recuperated thymi. These data demonstrate effects of developmental programming upon thymic involution. The recuperated group had longer thymic telomeres than controls (P < 0.001) at 22 d and at 3 mo, which was associated with increased expression of telomere-length maintenance molecules [telomerase RNA component (Terc; P < 0.01), P23 (P = 0.02), and Ku70 and Ku80 (P < 0.01)]. By 12 mo, recuperated offspring had shorter thymic telomeres than controls had (P < 0.001) and reduced DNA damage-response markers [(DNA-PKcs, Mre11 (P < 0.01), Xrcc4 (P = 0.02), and γ-H2ax (P < 0.001], suggesting failure of earlier compensatory responses. Our results suggest that low birth weight with rapid postnatal growth results in premature thymic maturation, resulting in accelerated thymic aging. This could lead to increased age-associated vulnerability to infection.—Tarry-Adkins, J. L., Aiken, C. E., Ashmore, T. J., Fernandez-Twinn, D. S., Chen, J.-H., Ozanne, S. E. A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.

Histological investigations on thymus of male rats prenatally exposed to bisphenol A

Bisphenol A is called as a endocrine-distrupting chemical because of the its steroid-like activity and it used in the construction of plastic containing materials. It is indicated that bisphenol A can pass the human serum, urine, follicular fluid, placenta and umblical cord as a result of the use of substances containing this agent. In this study, we aimed to investigate the effects of bisphenol A on the development of the thymus, a primary lymphoid organ which plays an important role in the specific immunity. The adult pregnant female rats were administered orally with bisphenol A (for 21 days) and postnatal thymus samples were obtained on day 21, 45 and 90 and were performed for histochemical and immunohistochemical staining for CD3, CD4, CD8 and CD79a and TUNEL assay for the apoptotic cells. Evaluation of all groups, CD3, CD4, CD8 and CD79a stainings were decreased in the experimental groups compared with control group. The apoptotic cells were determined in the all groups on day 90 as a result of the thymus involution. It is noted that there was not any histological and morphological damages in the rats prenatally exposed the bisphenol A. The effect of the bisphenol A is unknown in the future, but there is no problem in the adult rats.

The effect of dichloroacetate on male rat thymus and on thymocyte cell cycle

The study aim was to investigate the effect of dichloroacetate (DCA) on thymus and the thymocyte cycle in rats. Wistar male gonad-intact and castrated rats (4-5 weeks) were investigated in the following groups: (1) control; (2) treated with DCA; and (3) treated with the DCA and sodium valproate (NaVP) combination. Rats were treated for 4 weeks with DCA 200 mg/kg/day alone and 300 mg/kg/day of NaVP plus 200 mg/kg/day of DCA (every second week, beginning with NaVP). After the experiment, the thymus was weighted, and the thymus lobe was taken for thymocyte flow cytometry. In gonad-intact rats, the thymus weight of the control was higher than in rats treated with DCA (P <0.001) or with the NaVP-DCA combination (P <0.04); a comparison of thymus weight between DCA- and NaVP-DCA-treated groups revealed a higher thymus weight loss in the DCA-treated group (P <0.03). Flow cytometry shows that DCA treatment increased the percentage of cells in the G2-M phase (P <0.03) and reduced in G1-G0 (P <0.02). The DCA treatment effect was determined only in gonad-intact but not in castrated rats. The authors discuss the possible DCA and NaVP interaction mechanisms.

Can prenatal exposure to a 900 MHz electromagnetic field affect the morphology of the spleen and thymus, and alter biomarkers of oxidative damage in 21-day-old male rats?

We investigated the effects of a 900 Megahertz (MHz) electromagnetic field (EMF), applied during the prenatal period, on the spleen and thymus of 21-day-old male rat pups. Pregnant Sprague-Dawley rats were divided into control and EMF groups. We applied 900 MHz EMF for 1 h/day to the EMF group of pregnant rats. Newborn male rat pups were removed from their mothers and sacrificed on postnatal day 21. Spleen and thymus tissues were excised and examined. Compared to the control group, thymus tissue malondialdehyde levels were significantly higher in the group exposed to EMF, while glutathione levels were significantly decreased. Increased malondialdehyde and glutathione levels were observed in splenic tissue of rats exposed to EMF, while a significant decrease occurred in superoxide dismutase values compared to controls. Transmission electron microscopy showed pathological changes in cell morphology in the thymic and splenic tissues of newborn rats exposed to EMF. Exposure to 900 MHz EMF during the prenatal period can cause pathological and biochemical changes that may compromise the development of the male rat thymus and spleen.

Gonadal hormone dependent developmental plasticity of catecholamine:β2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis

The study was undertaken considering that: i) androgens affect β2-adrenoceptor (AR)-mediated catecholamine (CA) action in many tissues; and ii) peripubertal changes in both circulating androgen and thymic CA levels are implicated in rat thymic involution. Its aims were to: i) explore putative effects of the late prepubertal orchidectomy on thymic CA:β2-AR complex in young adult rats, and ii) delineate the direct effects of testicular hormone withdrawal on the CA:β2-AR complex from those elicited secondarily through altered influence of this complex components on each other's availability. Upon showing that prepubertal orchidectomy augmented the efficacy of thymopoiesis through increasing the thymocyte surface density of Thy-1, whose expression is negatively regulated by β2-AR-mediated signaling, we examined the effects of orchidectomy and 14-day-long propranolol (PROP) treatment in orchidectomized (ORX) and sham-ORX rats on thymic norepinephrine (NE) concentration and metabolism and β2-AR expression. Orchidectomy, despite an increase in the average NE amount per thymocyte and total thymocyte NE content, diminished thymic NE concentration. This decrease reflected the diminished density of CA-synthesizing nerve fibers, CD68+ macrophages, cortical (aminopeptidase A+), and medullary (UEA-1+) thymic epithelial cells (TECs) and their CA content (probably due to lessened TH expression accompanied by increased MAO-A expression). Moreover, orchidectomy decreased the surface β2-AR expression on thymocytes, CD68+ macrophages and OX-62+ dendritic cells, but increased its expression on the TECs. In sham-ORX rats, PROP reduced thymic NE concentration by diminishing TH expression in the thymic cells. Additionally, PROP in thymocytes and thymic stromal cells diminished and enhanced the β2-AR mRNA expression, respectively. However, in ORX rats PROP did not significantly affect CA(NE):β2-AR complex components. This indicated that prepubertal orchidectomy affects ability of young adult rats to respond to β-AR blockade by altering thymic NE and β2-AR availability. Collectively, the results showed that testicular hormones contribute to alterations in thymus/thymopoiesis during the critical peripubertal period by shaping modulatory sympathetic influence and CA autocrine/paracrine action within the organ.

Dose-dependent effects of carbendazim on rat thymus

In this study, the effects of carbendazim on the thymus in male rats were evaluated. Carbendazim was administered at 0, 150, 300 and 600 mg kg(-1) day(-1) doses by gavage to male rats for 15 weeks. Body weights of rats in all groups were recorded weekly during treatment. At the end of the experiment, the effects of carbendazim on the thymus were investigated histopathologically and morphologically. Also, based on these effects, change in immunolocalization of fibronectin (FN), which is a component of the extracellular matrix, was investigated immunohistochemically. Fibrosis and oedema were observed in the thymus of rats treated with 300 and 600 mg kg(-1) day(-1) doses of carbendazim. Also in this region, an increase in FN density was noted at the end of the immunohistochemical investigation. A decrease was observed in absolute and relative thymus weights of rats treated with carbendazim compared with the control group. While the decrease in absolute thymus weight was statistically significant in rats exposed to carbendazim at the highest dose, the decrease in relative thymus weights was statistically significant for all carbendazim doses.

Influences of surgical castration on the thymus of male rats

In previous studies, we have shown that castration of Sprague–Dawley rats enhances thymic weight through puberty whilst sex steroids reduce the castration-induced hypertrophy. In the current study, we have confirmed that castration enhances thymic growth compared to age-matched intact controls. In addition, immunoassays were used to measure thymosin α1 and thymosin β4 levels in sera from intact and castrate rats. Castrate animals displayed greater sera levels of thymosins compared to sera from intact animals. To test whether the enhanced thymic weight and increased levels of thymosins observed post-castration were able to influence immune function of castrate animals, concanavalin A was used in the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay to examine lymphocyte and thymocyte responses from both intact and castrate male rats. Responses of cells isolated from castrate rats demonstrated that lymphocytes and thymocytes were stimulated at low levels of concanavalin A (1.56–3.13 μg/ml for lymphocytes and 1.56 μg/ml for thymocytes) compared to the same cell types isolated from intact rats. Concentrations of concanavalin A ranging from 6.25 to 200 μg/ml produced no significant differences in response from intact and castrate animals.

The immune response evokes up- and down-modulation of beta 2-adrenergic receptor messenger RNA concentration in the male rat thymus.

Important alterations of noradrenergic activity are known to occur in specific brain regions and in different lymphoid tissues during the course of an immune response. Our recent characterization of the beta 2-adrenergic receptor (beta 2AR)-cAMP system of the rat thymus gland, the identification of a thymic beta 2AR gene expression, and the marked modulation of receptor mRNA concentration after castration and replacement with estrogen prompted us to study the ability of products of immune axis activation to modulate beta 2AR number, distribution, and expression in the male rat thymus. Moreover, the effect of adrenergic stimulation of adenylyl cyclase activity on thymus gland membrane preparations was measured. The beta 2AR present in the rat thymus undergoes marked changes in both number and distribution during the course of an immune response. At 3 days after antigenic challenge (injection of BSA in complete Freund's adjuvant), a sharp decrease of receptor number coupled with a significant loss of the autoradiographic reaction in the medullary compartment of the rat thymus gland were observed. These effects were followed by a significant increase in receptor density and number without changes in receptor affinity at 7 and 15 days post immunization, corresponding to the pick of the immune response. Parallel alterations in adenylyl cyclase activity were measured. Northern blot analysis, using a human beta 2AR cDNA as a probe, revealed dramatic alterations of the beta 2AR mRNA in the thymus, characterized by an approximately 75% decrease of mRNA level 3 days after immunization, and by a progressive increase at 7 and 15 days, with beta 2AR mRNA concentration rising to levels even higher than those found in control animals. These results suggest that the immune response evokes marked alterations of the thymic beta 2AR-cAMP signaling pathway. Moreover, antigenic stimulation triggers a down- and up-modulation of beta 2AR gene expression. Although it is presently unknown whether factor(s) released by immune axis activation act at the level of gene transcription to modulate adrenergic receptor function in the rat thymus, such down- and up-regulation of beta 2AR mRNA may play a role in the dynamic regulation of the immune response.

The immune response evokes up- and down-modulation of beta 2-adrenergic receptor messenger RNA concentration in the male rat thymus

The immune response evokes up- and down-modulation of beta 2-adrenergic receptor messenger RNA concentration in the male rat thymus

Evidence that somatostatin is localized and synthesized in lymphoid organs.

Because several peptides originally found in the pituitary as within the central nervous system have been localized in lymphoid tissues and because somatostatin (somatotropin-release-inhibiting hormone, SRIH) can act on cells of the immune system, we searched for this peptide in lymphoid organs. We demonstrated that SRIH mRNA exists in lymphoid tissue, albeit in smaller levels than in the periventricular region of the hypothalamus, the brain region that contains the highest level of this mRNA. SRIH mRNA was found in the spleen and thymus of male rats and in the spleen, thymus, and bursa of Fabricius of the chicken. Its localization in the bursa indicates that the peptide must be present in B lymphocytes since this is the site of origin of B lymphocytes in birds. The SRIH concentration in these lymphoid organs as determined by radioimmunoassay was greater in the thymus than in the spleen of the rat. These concentrations were 50 times less than those found in the periventricular region of the hypothalamus, the site of the perikarya of SRIH-containing neurons. In the chicken, as in the rat, the concentration of SRIH was greater in the thymus than in the spleen; it was present in the bursa of Fabricius, also in higher concentration than in the spleen. Fluorescence immunocytochemistry revealed the presence of SRIH-positive cells in clusters inside the white pulp and more dispersed within the red pulp of the spleen of both the rat and the chicken. The thymus from these species also contained SRIH-positive cells within the medulla and around the corticomedullary junction. In the chicken, there were large clusters of SRIH-positive cells in the medullary portion of each nodule of the bursa of Fabricius. Preabsorption of the primary antiserum or replacing this antiserum with normal rabbit serum verified the specificity of staining. Sequential immunostaining of the same sections from rat spleen using first SRIH antibody and subsequently a monoclonal antibody against a rat B-cell surface antigen revealed the presence of SRIH immunoreactivity in some, but not all, B cells. Other cell types in spleen not yet identified also stained positively with the SRIH antibody but were not reactive to monoclonal antibodies to rat Thy-1.1, a marker for all the thymic T lymphocytes. The possibility that SRIH is present in other populations of cells in the spleen cannot be ruled out. Sequential immunostaining of the same sections of rat thymus revealed the presence of SRIH immunoreactivity in a small population of T lymphocytes in the medulla, as revealed by the Thy-1.1 marker. The SRIH-positive cells were nonimmunoreactive when exposed to the B-cell marker; however, the possibility that SRIH is present in other cells was not investigated. Thus, our results indicate that SRIH is synthesized and stored in cells of the immune system. SRIH may be secreted from these cells to exert paracrine actions that alter the function of immune cells in spleen and thymus.

In vitro metabolism of 4-14C-testosterone by thymus of male rats of various ages.

Stoffwechseluntersuchungen von 4-14C-Testosteron wurden in vitro mit Thymushomogenaten, die aus 2, 3, 4, 5, 7 und 10 Wochen alten mannlichen Ratten gewonnen wurden, durchgefuhrt. Die Radiochromatogramme der Metaboliten zeigten ein gleichartiges Bild.

Histamine, magnesium deficiency, and thymic tumors in rats.

Histamine was measured in the plasma, liver, and thymus of male rats fed a magnesium-deficient diet for 65 days. Histological study of the thymus was also performed. Histamine levels in plasma and tissue increased rapidly and reached a maximum after 10 days of deficiency. Later on, the level of histamine in deficient animals decreased and fluctuated but was usually higher than in the controls. One rat killed after 60 days of deficiency showed a very large thymus, weighing 1.8 g, which extended into the thoracic cavity. Histological study revealed a complete replacement of the normal thymic cells by large basophilic lymphocytes invading the neighboring organs including the heart muscle. The tumor was transplanted successfully in normal rats receiving a well-balanced diet. Another smaller tumor was found in an animal killed at 65 days. Thymuses of control animals were all normal. The development of tumors of the thymus in magnesium-deficient rats is discussed in connection with the changes in tissue histamine.

The effect of relatively large doses of sesame oil on oxygen consumption and the antagonistic action of adrenocortical extract.

Although it is generally concluded on the basis of the literature that sesame oil is physiologically inactive as a vehicle for fat soluble substances, there are indications that it is not as physiologically inactive as generally believed. Sesame oil in varying dosages has been reported to cause marked visceral damage in sarcoma bearing rats (Pollia, 1937); to shorten the mean survival time of adrenalectomized rats by 1.6 days as compared with their controls (Spurr and Kochakian, 1939); to produce toxic effects and death in normal rats as quickly as ten days after beginning the injections (Bruce and Tobin, 1940); to induce atrophy of the thymus in male rats (Clausen, 1940); to cause atrophy of the seminal vesicles and prostate gland in young mice (Crafts, 1942); and to stimulate the germinal epithelium of the ovary in young mice (Stein and Allen, 1942). It is the purpose of this investigation to show the effects on oxygen consumption of the whole organism