Rat Thymus Research Articles

I Dentification Immunohistological Changes in the Thymus Gland of Male and Female Rats With Indocrine Glands Disorder

Endocrine disorders is the result of a hormone imbalance, a condition characterized by a gland producing too much or too little of a hormone. This imbalance can be caused by:Issues with the endocrines feedback system−its main job is to keep hormones in the body perfectly balanced but it can malfunction and cause an imbalance a genetic disorder or infection or disease or injury to an an endocrine gland.The study amied to know the changes that occur in the thymus gland as a result of endocrine disorders in order to explain and analyze them accurately,as well as an immunological comparison between males and females.Twenty−four male and female rats Rattus norvegicus were divided into three groups of eight rats each : The first group (G1) received normal saline for 21 dayꓼ The second group male(G2), rats were given 6 mg / kg metoclopramide by intraperitoneal injection for hyperprolactinemia induction for 21 daysꓼ The third group femals (G3)was given metoclopramide 6 mg / kg intraperitoneally to induce hyperprolactinemic rats.After the end of experimental [21 days ], Measure prolactin hormone, and the thymus gland was removed, processed and examine for histomorphological changes. The result of the study revealed that is a significant (p<0.05) in prolactin and( WBC) in the two hyperprolactinemia group when compared with the control group.And when compared a group of hyperprolactinemia the males and agroup hyperprolactin females.Note a significant difference(increase)in the male group compared to the female group.And the resuit of the study showed asignificant decrease(p<0.05) in weight and size the thymus gland in hyperprolactinemia male and female group compared with the control group.The histologicale study in male and female laboratory rats of the two hyperprolactinemia group also showed clear histological changes compared to the negative control group,reprsented the cortex area increased compared with the medulla area ,where the cortex−to−medulla ratio was about 3:1 .The limited numbers of epithelial cells were observed in the medulla area where the increase in lymphocyte numbers was significantly observed.Also, Hassall‘s corpuscles were not observed in the medulla.AS note the limited deposition or almost absence of collagen fibre in the medulla area.The study concluded endocrine disruption has a significant and noticeable effect on the size and weight of the thymus gland on the one hand and a histological effect on the other hand.

The Structure Of The Rat Thymus During Late Postnatal Ontogenesis And Its Changes When Exposed To An Energy Drink

The Structure Of The Rat Thymus During Late Postnatal Ontogenesis And Its Changes When Exposed To An Energy Drink

ФУНКЦИОНАЛЬНЫЕ И СТРУКТУРНЫЕ ИЗМЕНЕНИЯ ТИМУСА КРЫС ПРИ ВОЗДЕЙСТВИИ РАЗЛИЧНЫХ ДОЗ ЭНДОКРИННОГО ДИСРАПТОРА

In recent years, there has been a significant increase in the number of diseases associated with impaired functioning of the immune system in the world. One of the main reasons for this can be considered environmental pollution by endocrine disruptors. The most common disruptor on the planet is DDT. Its ubiquitous content in food, water and soil is noted, which makes the study of the effect of its background doses on the body extremely relevant. Systemic consumption of low doses of the disruptor DDT leads to significant changes in the structural and functional characteristics of the rat thymus, which are manifested by increased death of lymphocytes and reticuloepitheliocytes, in the mechanisms of death of which the p53-dependent pathway of apoptosis is involved, as well as a decrease in the proliferative activity of thymocytes, i.e., it is capable of having an immunotoxic effect on the body. These data show that the maximum permissible levels of DDT in food are not safe for the body's immune system.

Effect of Flavonols of Aronia melanocarpa Fruits on Morphofunctional State of Immunocompetent Organs of Rats under Cyclophosphamide-Induced Immunosuppression.

Aronia melanocarpa berries contain many compounds with potential benefits for human health. The food flavonoids quercetin and rutin, found in significant amounts in the fruits of A. melanocarpa, are known to have favourable effects on animal and human organisms. However, data on the effect of flavonols isolated from black chokeberry on immune functions during immunosuppression are not available in the literature. Thus, the aim of this study was to evaluate the effect of flavonol fraction isolated from A. melanocarpa fruits, in comparison with pure quercetin and rutin substances, on the dysfunctional state of rat thymus and spleen in immunodeficiency. The study was performed on Wistar rats. The animals were orally administered solutions of the investigated substances for 7 days: water, a mixture of quercetin and rutin and flavonol fraction of A. melanocarpa. For induction of immunosuppression, the animals were injected once intraperitoneally with cyclophosphamide. Substance administration was then continued for another 7 days. The results showed that under the influence of flavonols, there was a decrease in cyclophosphamide-mediated reaction of lipid peroxidation enhancement and stimulation of proliferation of lymphocytes of thymus and spleen in rats. At that, the effect of the flavonol fraction of aronia was more pronounced.

Protective effects of oyster polypeptide on cyclophosphamide-induced immunosuppressed rats.

Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (1H-NMR) urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. Oyster polypeptide restored the body weight and the structure of spleen and thymus in rats with cyclophosphamide-induced immunosuppression. It upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as interleukin‑6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased the numbers of CD3+ and CD4+ T cells in the immunosuppressed rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urine, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally, a combination of metabolomics and microbiomics found that the metabolism of taurine and hypotaurine, and the metabolism of alanine, aspartate, and glutamate were disturbed, but these metabolic pathways were restored by OP. This study demonstrated that OP had immunoprotective effects in rats with cyclophosphamide-induced immunosuppression by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provide a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. © 2024 Society of Chemical Industry.

Mutation of the Thap4 gene causes dwarfism and testicular anomalies in rats and mice.

The petit (pet) locus is associated with dwarfism, testicular anomalies, severe thymic hypoplasia, and high postnatal lethality, which are inherited in autosomal recessive mode of inheritance in rats with a Wistar strain genetic background. Linkage analysis localized the pet locus between 98.7Mb and 101.2Mb on rat chromosome 9. Nucleotide sequence analysis identified 2bp deletion in exon 2 of the Thap4 gene as the causative mutation for pet. This deletion causes a frameshift and premature termination codon, resulting in a truncated THAP4 protein lacking approximately two-thirds of the C-terminal side. Thap4 is expressed in various organs, including the testis and thymus in rats. To elucidate the biological function of THAP4 in other species, we generated Thap4 knockout mice lacking exon 2 of the Thap4 gene through genome editing. Thap4 knockout mice also exhibited dwarfism and small testis but did not show high postnatal lethality. Thymus weights of adult Thap4 knockout male mice were significantly higher compared to wild-type male mice. Although Thap4 knockout male mice were fertile, their testis contained seminiferous tubules with spermatogenesis and degenerative seminiferous tubules lacking germ cells. Additionally, we observed vacuoles in seminiferous tubules, and clusters of cells in the lumen in seminiferous tubules in Thap4 knockout male mice. These results demonstrate that spontaneous mutation of Thap4 gene in rats and knockout of Thap4 gene in mice both cause dwarfism and testicular anomalies. Thap4 gene in rats and mice is essential for normal testicular development, maintaining spermatogenesis throughout the entire region of seminiferous tubules.

Changes in the Cellular Composition of the Rat Thymus 90 Days After Urethane Injection Against the Background of Selenium Intake

The aim of the study is to assess the cellular composition of rat thymus when isolated administration of selenium, urethane and combined exposure to two factors. Material and methods. The study was performed on 34 male Wistar rats, which were divided into 4 groups: 1 – intact, 2 – rats, which received selenium only for 1 month, 3 – animals, which were injected once intraperitoneal urethane, 4 – rats with combined selenium and urethane action. Histological preparations of the thymus were prepared according to generally accepted methods and further evaluated by the method of review microscopy, morphometry, immunohistochemical reactions, electron microscopy, statistical processing of data. Results. Ninety days after selenium, the rat thymus structure is slightly different from intact animals. The introduction of urethane leads to the development of excitation involution of the thymus, which is characterized by morphological changes, and manifests itself in a change in the shape of the organ lobes, in the expansion of the intercole gaps and in the fat tissue thereof, hyperplasia of the cortical substance of the thymus by increasing the number of mature lymphocytes, epithelial cells positive to pancytokeratin. At the ultramicroscopic level, the thymus lymphocyte decreases its nuclear-cytoplasmic index, and increases the number of mitochondria that have a light matrix with a small amount of crystal. Apoptotic bodies and a large number of electron-transparent vacuoles are visualized. When combined, the thymus structure differs from the intact group by an enlarged brain substance, but the number of epithelial cells that are positive to pancytokeratin and Ki67+-cells, as well as cells that express apoptosisregulating protein, decreases. Electron microscopy also indicates a large amount of mitochondria, but with welldefined crystals, when combined with selenium and urethane. There are a small number of electron-transparent vacuoles. Conclusion. The obtained data make it possible to draw a conclusion about the positive influence of the exchange rate of selenium on the T-cell link of immunity, at least for this period of study. In the course of the experiment, it was found that, against the background of the development of the adenoma of the lung caused by the introduction of urethane, at the stage of alveolar epithelium dysplasia signs of excitant thymus involution were detected. When selenium and urethane are combined, less pronounced changes are observed in the examined organ than in the isolated administration of urethane.

Therapeutic effect of notoginseng saponins before and after fermentation on blood deficiency rats.

Notoginseng saponins (NS) are the active ingredients in Panax notoginseng (Burk.) F.H. Chen (PN). NS can be transformed depending on how the extract is processed. Fermentation has been shown to produce secondary ginsenosides with increased bioavailability. However, the therapeutic effect of fermented NS (FNS) requires further study. The present study compared the compositions and activities of FNS and NS in blood deficiency rats, which resembles the symptoms of anemia in modern medicine, induced by acetylphenylhydrazine and cyclophosphamide. A total of 32 rats were randomly divided into control, model, FNS and NS groups. A blood deficiency model was established and then treatment was orally administered for 21 days. The results of component analysis indicated that some saponins transformed during the fermentation process resulting in a decrease of notoginsenoside R1, and ginsenosides Rg1, Rb1 and Re, and an increase in ginsenosides Rd, Rh2, compound K, protopanaxadiol and protopanaxatriol. The animal results showed that both FNS and NS increased the number of white blood cells (WBCs), red blood cells, hemoglobin, platelets and reticulocytes, and the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO) and thrombopoietin (TPO), decreased the G0/G1 phase and increased G2/M phase, and decreased the apoptosis rate of bone marrow (BM) cells, which suggested a contribution to the recovery of hematopoietic function of the BM cells. FNS and NS increased the protein expression levels of the cytokines IL-4, IL-10, IL-12, IL-13, TGF-β, IL-6, IFN-γ and TNF-α, and the mRNA expression levels of transcription factors GATA binding protein 3 and T-box expressed in T cell (T-bet). FNS and NS treatment also increased the number of CD4+ T cells, and decreased the enlargement of the rat spleen and thymus atrophy, which indicated a protective effect on the organs of the immune system. The results of the present study demonstrated that compared with NS, FNS showed an improved ability to increase the levels of WBCs, lymphocytes, GM-CSF, EPO, TPO, aspartate aminotransferase, IL-10, IL-12, IL-13 and TNF-α, and the mRNA expression levels of T-bet, and decrease alanine aminotransferase levels. The differences seen for FNS treatment could arise from their improved bioavailability compared with NS, due to the larger proportion of hydrophobic ginsenosides produced during fermentation.

THE INFLUENCE OF ACUTE CEREBRAL BLOOD CIRCULATION DISORDERS IN THE POOL OF CAROTID ARTERIES ON THE RNA CONTENT IN THE CELLS OF THE LYMPHOID POPULATION OF THE RATS’ THYMUS OF DIFFERENT AGE GROUPS

The aim of the work – to find out the age-related features of the response of RNA cells ofthe lymphoid population of the thymus to an acute disturbance of cerebral blood flow inthe pool of carotid arteries in six- and nine-month-old rats.Materials and methods. Acute cerebrovascular accident was simulated in 6- and9-month-old white non-linear laboratory rats by bilateral carotid artery clamping for 20min. followed by reperfusion. The thymus was taken on the 12th day of the postischemicperiod, fixed in Buen’s solution, after standard histological processing it was embedded inparaffin, and serial sections with a thickness of 5 μm were made. After deparaffinization,rehydration, and staining with hallocyanine- chromium alum according to Einarson,histological sections were analyzed in a digital image analysis system VIDAS-386(Kontron Electronik, Germany) with a fluorescent microscope AXIOSKOP (Zeiss,Germany). Total RNA content was expressed in units of optical density (EOP per 1 mm2). The results. In the cells of the lymphoid population of all structural and functional zones ofthe thymus of control rats of both age groups, an increase in RNA content was establishedin the direction from immature to more mature classes (p<0.05). This regularity persistsin the post-ischemic period. In the cells of the lymphoid population of the subcapsular anddeep cortical zones of the thymus, the RNA content significantly prevails in six-month-oldrats, in intralobular perivascular spaces – in nine-month-old rats, and in the medullaryzone there are no age differences. Postischemic changes in RNA content in six-month-oldrats in the subcapsular zone and intralobular perivascular spaces of the thymus consistin its decrease in immature cell classes and its increase in mature small thymocytes(р<0.05); in the deep cortex – in growth in all classes of thymocytes (p<0.05). In ninemonth-old animals, the differences were in the increase in RNA content in the subcapsularzone and in less mature middle thymocytes, in the deep cortex – in a decrease in RNAcontent in all classes, except small thymocytes, in intralobular perivascular spaces – ina decrease in RNA content in all classes of thymocytes (p<0.05 for all cases). In themedullary zone of animals of both age groups, changes are unidirectional (decrease inRNA content, p<0.05).Conclusion. Age differences in the nature of postischemic changes in the content of RNAin thymocytes are present in all structural and functional zones of the gland, with theexception of the medullary, in which the changes were unidirectional in both age groups.

Cilomilast, a PDE4 Inhibitor, Suppresses CD4+ and CD8+ T Cell Proliferation in the Thymus and Spleen of Rats: Mechanism of Glutathione Reduction

Cilomilast, a PDE4 Inhibitor, Suppresses CD4+ and CD8+ T Cell Proliferation in the Thymus and Spleen of Rats: Mechanism of Glutathione Reduction

AGE CHARACTERISTICS OF CHANGES IN THE LYMPHOID POPULATION STRUCTURE OF THE RATS’ THYMUS AFTER ACUTE DISTURBANCE OF CEREBRAL BLOOD FLOW IN THE BASIN OF CAROTID ARTERIES

Abstract. Today, the most common causes of disability and mortality on the planet include acute disorders of cerebral blood circulation, the spectrum of which is dominated by ischemic lesions. Advances in neuroimmunology and neuroimmunopathology have made it possible to attribute cerebral blood circulation disorders to immune- dependent diseases of the nervous system, therefore, the emphasis in the search of new approaches to the eff ectiveness increase of stroke therapy has shifted from the correction of local changes in the brain itself to the reaction of the immune system organs, as a possible target of pharmacological eff ects, that will make it possible to reduce the secondary death of neurons as a result of infl ammation.The purpose of the work. to investigate the age-specifi c changes in the structure of the lymphoid population of the thymus after acute disruption of cerebral blood fl ow in the basin of the carotid arteries in six- and ninemonth-old rats.Material and methods. Acute cerebrovascular accident was simulated in 6- and 9-month-old white nonlinear laboratory rats by bilateral carotid artery clamping for 20 min. followed by reperfusion. The thymus was taken on the 12th day of the postischemic period, it was fi xed in Buen’s solution, after standard histological processing, serial sections with a thickness of 5 μm were made, stained with hematoxylin- eosin. In the subcapsular, deep cortical zones, intralobular perivascular spaces and the medullary zone of the thymus, the structure of the lymphoid population (density of diff erent classes of thymocytes per 1 mm2) was studied in the digital image analysis system VIDAS-386 (Kontron Electronik, Germany) with a fl uorescent microscope AXIOSKOP (Zeiss, Germany) in automatic mode.The results. In the structure of the lymphoid population of all structural and functional zones of the thymus, small lymphocytes predominate. Age-related diff erences in the structure of the lymphoid population of the thymus of the control groups consist of lower indicators of the density of medium and small thymocytes in all investigated zones of the gland of animals of the older age group, with the exception of the subcapsular, in which the density of small thymocytes is higher in nine-month-old rats. On the 12th day after simulation of ischemia- reperfusion of the brain injury the number of destructive thymocytes and thymocytes with the signs of apoptosis increases in the subcapsular and deep cortical zones of the thymus of six-month-old rats, but in nine-month-old rats in all zones of the gland, except the brain, the density of destructive and apoptotic cells decreases.Conclusions. Ischemic- reperfusion injury of the brain modifi es the structure of the lymphoid population of the thymus of rats, and the nature of these modifi cations is determined by age and structural and functional zones of the gland.

Kinetic properties of E-NTPDase activity in lymphocytes isolated from bone marrow, thymus and mesenteric lymph nodes of Wistar rats.

Plasma membrane anchored nucleotidases (E-ATPDases), as the E-NTPDase family, could hydrolyze and regulate the pericellular levels of nucleotides in lymphocytes. Each immune organ has a different microenvironment and display lymphocytes with different functions and phenotypes. Considering the different functions of each resident subpopulations of lymphocytes, the E-ATPDases activities in bone marrow (BML), thymus (TL) and mesenteric lymph node (MLL) lymphocytes of Wistar rats were characterized. The hydrolysis of extracellular nucleotides (eATP and eADP) showed linearity in time of reaction between 0 and 120min, and concentration of lymphocytes expressed in proteins between 1 and 6μg protein in the reaction medium. The optimal activity was attained at 37°C in a pH value of 8.0. The necessity of the cofactors Ca2+ and Mg2+ for the enzymatic activity was confirmed through a curve of concentration of 0-1000µM in the reaction medium, with both cofactors showing similar effects in the enzymatic activity. The Chevillard plot revealed that the hydrolysis of eATP and eADP occurred at the same active site of the enzyme. The analyses of E-ATPDases inhibitor and enzyme specificity showed possible involvement of E-NTPDase isoforms -1 and -2 in the isolated cells. Furthermore, different kinetic behavior of the nucleotide hydrolysis in each resident subpopulation lymphocyte was observed in this study, as MLL showed the higher Vmax with the lowest km values, while TL had the lowest Vmax and high km values. The kinetic values for E-NTPDase activity of each immune tissue lymphocytes can be an important therapeutic target for numeral immune-related diseases.

Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation.

Herein, we investigated whether L-ascorbic acid (L-AA) and α-tocopherol (α-T) co-administration has the potential to alleviate arsenic-induced immunotoxicities in the thymus, spleen, and circulating leukocytes. Forty-eight adult male Wistar rats were randomly divided into four groups before the treatment: group I (control); group II (sodium arsenite, 3mg/kg/day/rat); group III (sodium arsenite + L-AA (200mg/kg/day/rat) and α-T (400mg/kg/day/rat)); group IV (L-AA and α-T). The result showed that sodium arsenite exposure (consecutive 30days) caused weight reduction, structural alterations in the thymus and spleen, accompanied by a decrease in thymocyte and splenocyte count. Decreased superoxide dismutase and catalase activity, increased malondialdehyde and protein-carbonyl content, reduced Nrf2 and Bcl2 expression, and increased p-ERK, NF-kβ, Bax, and cleaved-caspase-3 expression were also observed in the thymus and spleen of arsenic-exposed rats. Enhanced plasma ACTH and corticosterone, ROS-induced apoptosis of lymphocytes were also observed. L-AA and α-T co-administration has the potential to abrogate the deleterious impact of arsenic on the thymus, spleen, and circulating lymphocytes. Whole transcriptome analysis of leukocytes revealed that arsenic treatment augmented the expression of Itga4, Itgam, and MMP9 genes, which might help in transient migration of the leukocytes through the endothelial cell layer. Co-administration with L-AA and α-T maintained Itga4, Itgam, and MMP9 gene expression within leukocytes at a lower level.

CISPLATIN AND PROGESTERONE SEPARATE AND JOINT ACTION ON RAT THYMUS NUCLEAR PHOSPHOLIPIDS COMPOSITION AND CONTENT

The antitumor agent cisplatin and progesterone separate and joint action on content of total phospholipids and their individual fractions in nuclei from rat thymus cells were investigated. When used separately, cisplatin and progesterone exhibit its own distinctive properties. Cisplatin reduces, and progesterone, on the contrary, increases the content of total phospholipids. When used together, the effects of these drugs are summed up. Thus total phospholipid content of rat thymus cell nuclei increases by 17% after the joint injection of cisplatin and progesterone. These changes have different effects on quantities of individual phospholipid fractions. It is assumed that the effects of cisplatin and progesterone, both in their separate and joint action, can be mediated by quantitative changes in internuclear lipids that in turn can regulate the main functions of the cell nuclei.

HIgD-Fc-Ig fusion protein regulates T cell functions by inhibiting TCR signaling pathway in adjuvant arthritis rats.

This study aimed to investigate the effect of hIgD-Fc-Ig on TCR-Lck-Erk activated by IgD in adjuvant arthritis (AA) rats. Wistar rats were divided into the normal, AA model, hIgD-Fc-Ig (1mg/kg, 3mg/kg and 9mg/kg) and Etanercept (3mg/kg) groups. The overall index of AA rats was measured every 3days. The pathologic examination of knee joints and the proliferation of the spleen and thymus of AA rats were detected by H&E staining and CCK-8. The blood flow signal of knee joints of experimental rats was examined by US. The articular bone injury was detected by X-ray. The changes in PBMCs and spleen T cell subsets were detected by flow cytometry. The expression of CD3ε, p-Lck, p-Zap70, Ras, and p-Erk in rat spleens was detected by immunofluorescence and WB. Rat spleen T cells or Jurkat cells treated by IgD to observe the effect of hIgD-Fc-Ig on TCR and its downstream protein expression. The results showed that hIgD-Fc-Ig had a therapeutic effect on AA rats by reducing the secondary inflammation, improving pathological changes. hIgD-Fc-Ig can reduce the ratio of Th cells of PBMCs of AA rats, the ratio of Th, Th1, Th17 cells and increase the ratio of Th2, Treg cells of AA rat spleens. hIgD-Fc-Ig could down-regulate the expression of CD3ε, p-Lck, p-Zap70, Ras, p-Erk in vivo or in vitro. In conclusion, hIgD-Fc-Ig could alleviate the symptoms of AA rats and regulate T cells through TCR-Lck-Erk signaling pathway and maybe a new promising biological agent for RA.

<b>RETRACTION</b>: Intrinsic innervation and dopaminergic markers after experimental denervation in rat thymus

On behalf of the coauthors and with much regret, I must retract our publication entitled "Intrinsic innervation and dopaminergic markers after experimental denervation in rat thymus" published in European Journal of Histochemistry 2010;54(2):e17 for the following reason: Unfortunately, now, after thirteen years, we have realized that some microphotographs published in the paper have been processed to improve the presentation of the images. The three surviving authors of the paper agree that the processing of the presentation images is against the COPE Ethical Editorial Standard, although the presentation images do not alter the integrity of methodological procedures and the results of the research work, obtained from the direct analysis of slides under microscope and rigorous statistical analysis of data; therefore, we, the authors of the above indicated paper, request the retraction of the publication. We apologize for what happened. Maurizio Sabbatini Dip. di Scienze e Innovazione Tecnologica (DISIT) Università del Piemonte Orientale Alessandria, Italy.

Haematopoietic and Immunomodulatory Activity of Sap of Borassus flabellifer against Cyclophosphamide Mediated Haematotoxicity and Immunosuppression in Wistar Rats

Recent scientific evidence recommends that many of the adverse effects of chemotherapy can be prevented by remedying treatment with antioxidants, minerals, carbohydrates, proteins, and organic acids. The current research was performed to assess haematopoietic and immunomodulatory effects using sap of traditional tree, Borassus flabellifer, in cyclophosphamide induced haematotoxicity and immunosuppression in wistar rats. For eleven consecutive days, the animals were orally pre-treated with Borassus flabellifer sap (3.6 mL/kg). These animals were intra-peritoneally injected on the sixth day with cyclophosphamide (150 mg/kg) and sacrificed five days later. On the final day of the trial, blood samples were obtained from each rat and carried out evaluation of haematological (red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, reticulocytes & serum iron content) and immunomodulatory (total leucocyte count, cellular immune response & tumor necrosis factor-α) parameters. To determine their index values, each rat's thymus and spleen were separated. By elevating red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, reticulocytes & serum iron content, sap of Borassus flabellifer demonstrated an important protective role in cyclophosphamide mediated haematotoxicity. It has also shown substantial resistance against immunosuppression caused by cyclophosphamide by increasing the immunity boosting white blood cells and decreasing the hypersensitivity reaction and tumor necrosis factor-α level at the 3.6 mL/kg dose. The current research shows that therapy with traditional Borassus flabellifer sap has a major protective effect against oxidative stress, haematotoxicity and immunosuppression against cyclophosphamide induced haematotoxicity and immunosuppression.

Histological study of the role of CD34+ stem cells and mast cells in cyclophosphamide-induced thymic injury in rats and the possible attenuating role of melatonin

Cyclophosphamide (CP) is an anticancer drug that adversely affects immunity and thymus structure. Melatonin is a hormone secreted by the pineal gland. It boosts immunity and has antioxidant properties. Therefore, the present study was conducted to investigate the possible protective effect of melatonin on CP-induced changes in the rat thymus. Forty male albino rats were used and divided equally into four main groups. Group I was the control group. Group II (melatonin group) received melatonin at a dose of 10 mg/kg body weight/day by intraperitoneal injection throughout the experimental period. Group III (CP group) received 200 mg/kg body weight CP by a single intraperitoneal injection. Group IV (CP + melatonin group) received melatonin intraperitoneally at a dose of 10 mg/kg body weight/day starting 5 days prior to CP injection until the end of the experiment. All rats were euthanized 7 days after CP injection. Administration of CP in group III resulted in depletion of the cortical thymoblasts. In addition, CD34-immunopositive stained stem cells decreased and mast cell infiltration increased. Electron microscopy showed degeneration of thymoblasts and vacuolization of epithelial reticular cells. Administration of melatonin with CP in group IV showed considerable protection of thymic histology. In conclusion, melatonin may protect against CP-induced thymic injury.

Differences in Age-Related Changes in the Thymus in Rats Developmentally Exposed to Endocrine Disrupter Dichlorodiphenyltrichloroethane.

We studied features of age-related changes in the thymus of mature male Wistar rats developmentally exposed to the endocrine disruptor dichlorodiphenyltrichloroethane (DDT). The study was carried out at the stage of early thymus involution. Differences in the thymus morphology associated with imbalance of morphogenetic processes in the cortex and medulla were observed after puberty in rats developmentally exposed to DDT. Increased proliferation of thymocytes, higher content of lymphoblasts, and concomitant decrease in T-cell migration in comparison with the control were found. Our findings indicate lower functional maturity of the thymus and prolonged disorders in the program of postnatal thymus development induced by the endocrine disruptor DDT.

Growth hormone enhances the CD34+ stem cells repopulation of the male albino rat thymus gland in cyclophosphamide induced injury: immunohistochemical and electron microscopic study

ABSTRACT Cyclophosphamide (CP) is a chemotherapeutic drug that has a harmful effect on the immune system. Growth hormone (GH) is a peptide hormone that can enhance thymic functions in cases of immunosuppression. Therefore, the present study was performed to study the possible protective effect of growth hormone on cyclophosphamide-induced changes in the rat thymus gland. Sixty-four adult male albino rats were used and divided into three main groups. Group I (Control group). Group II (CP group) received 200 mg/kg body weight CP by a single intra-peritoneal injection. Group III (CP& GH group) received GH in a dose of 2 mg/kg body weight/day by subcutaneous injection starting 5 days before cyclophosphamide injection till the end of the experiment. Administration of CP (Group II) resulted in marked histopathological changes in thymus. Thymic cortex showed depletion of thymoblasts. There was a decrease in CD34 immune positively stained stem cells and an increase in CD68 immune positively stained macrophages. Ultrastructurally, thymoblasts were markedly degenerated and the most of epithelial reticular cells were vacuolated. Administration of GH (group III) showed preservation of the histological structure of the thymus. In conclusion, growth hormone could protect against cyclophosphamide induced thymic damage.