Effect of Shenling Baizhu San on Lipid Metabolism and Intestinal Barrier of UC with Spleen Deficiency

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease and spleen-deficiency (SD) is considered as the common Chinese medicine syndrome of UC. However, the mechanism of Shenling Baizhu San (SLS) on UC with spleen-deficiency has not been clarified. The aim of this study was to explore the influence of SD on lipid metabolism and intestinal barrier in UC mice and reveal the underlying mechanism of SLS on UC mice with spleen-deficiency. Methods: The male C57BL/6 mice were randomly divided into control group, Dextran Sulfate Sodium (DSS) group, DSS+SD group and SLS group. The data of disease activity index, body weight and length of colon were recorded to evaluate the colitis, the spleen and thymus weight were recorded to evaluate the spleen-deficiency, the serum metabolites were detected by untargeted metabolomics, the tight junction and intestinal mucus barrier were evaluated by Alcian Blue-Periodic acid Schiff staining and immunochemical, the activity of ATPase were detected by spectrophotometer, the proinflammatory factors and the copy number of mitochondrial DNA were detected by RT-PCR, the relative expression of Sirtuin 1 (SIRT1), Peroxisome proliferator-activated receptor γcoactivators-1α (PGC-1ɑ) and Mitochondrial transcription factor A (TFMA) were detected by RT-PCR and western blot. Results: The mice treated by compound method showed decreased spleen and thymus weight as well as more serious intestinal inflammation than DSS group. Compared with DSS+SD group, SLS improved intestinal inflammation and spleen deficiency, ameliorated lipid metabolism and intestinal barrier as well as promoted expression of SIRT1, PGC-1ɑ and TFMA in UC mice with spleen-deficiency. Conclusion: SLS could be considered as an effective treatment for spleen-deficiency in UC and its underlying mechanism might be related to improve lipid metabolism and intestinal barrier through mediating SIRT1/PGC-1ɑ pathway.

Zinc supplementation prevents the development of thymic involution induced by tumor growth in mice

Aim. The aim of this study was to investigate the influence of zinc supplementation on the development of thymic involution during the growth of transplantable tumor in mice. Materials and methods. Inbred C3HA mice after subcutaneous syngeneic hepatoma 22a inoculation received zinc sulfate with drinking water. After 3 weeks of tumor growth animals were killed, and evaluated for zinc content in serum blood samples, thymus status and parameters of tumor growth. Results. At the 21 day of tumor 22a growth weight and cellular content of the thymus were decreased by 3 times and endogenous zinc content in samples of blood serum was decreased by 1,9 times. Oral zinc sulfate supplementation at concentration of 22 mkg/ml in drinking water during 3 weeks, started from the first day after tumor inoculation, increased thymus weight and cellularity as well as serum zinc content. At the same time, it did not influence tumor size and survival rate of mice with hepatoma 22a. As a possible mechanism of zinc action, we studied the influence of zinc supplementation on the activity of two anti-oxidative defense enzymes: Cu,Zn-superoxide dismutase and catalase in the thymus. Zinc supplementation had no influence on these parameters, both remained at a higher level in tumor-bearing mice. Conclusion. Oral zinc supplementation in hepatoma 22a bearing mice induced retards the development of thymic involution with no influence on the tumor growth per se. The study allows to suggest that oral zinc administration may be considered as a prospective strategy for thymus reconstitution in oncology patients.

Effect of Aflatoxin Contaminated Feed for 40 Days on Anatomy and Histopathology of the Thymus of Laying Hens in the Starter Phase

The purpose of this study was to determine the effect of aflatoxin contaminated feed given for 40 days on the anatomy and histopathology of the thymus of laying hens in the starter phase. A total of 36 DOC laying hens were divided into two groups (P0 and P1). P0 (control group) was given 100% basal starter feed CP 521 and P1 (treatment group) was given 80% basal feed CP 524 plus 20% aflatoxin contaminated feed. Feeding contaminated with aflatoxin was carried out for 40 days, starting on the 20th to the 60th day after the DOC of laying hens was adapted for 20 days. The time of surgery in this study was carried out on the 20th, 40th, and 60th days, where at each surgery time the thymus organ was taken to collect weight data and histopathological preparations were made. The thymus weights based on time showed a significant decrease, but the intergroup thymus weights did not show a significant decrease. The decrease in thymus weight is caused by the involution process. Microscopic observations based on increased cell debris and congestion showed that P0 did not show a significant difference, but P1 showed a significant difference (p>0.05) on the 40th and 60th days. The conclusion in this study was that as much as 20% of feed contaminated with aflatoxins had not affected changes in thymus weight but had shown damage to the histopathological structure of the thymus.

The effects of estradiol are modulated in a tissue-specific manner in mice with inducible inactivation of ERα after sexual maturation

Mouse models with lifelong inactivation of estrogen receptor-α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other nonskeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAGG-Cre-ER and ERαflox/flox mice. Tamoxifen-induced ERα inactivation after sexual maturation substantially reduced ERα mRNA levels in cortical bone, trabecular bone, thymus, uterus, gonadal fat, and hypothalamus, in CAGG-Cre-ERαflox/flox (inducible ERαKO) compared with ERαflox/flox (control) mice. 17β-estradiol (E2) treatment increased trabecular bone volume fraction (BV/TV), cortical bone area, and uterine weight, while it reduced thymus weight and fat mass in ovariectomized control mice. The estrogenic responses were substantially reduced in inducible ERαKO mice compared with control mice on BV/TV (−67%), uterine weight (−94%), thymus weight (−70%), and gonadal fat mass (−94%). In contrast, the estrogenic response on cortical bone area was unaffected in inducible ERαKO compared with control mice. In conclusion, using an inducible ERαKO model, not confounded by lack of ERα during development, we demonstrate that ERα expression in sexually mature female mice is required for normal E2 responses in most, but not all, tissues. The finding that cortical, but not trabecular bone, responds normally to E2 treatment in inducible ERαKO mice strengthens the idea of cortical and trabecular bone being regulated by estrogen via different mechanisms.

Changes in mouse thymus after exposure to tube-restraint stress

The thymus is the primary lymphoid organ involved in the regulation of the immune and endocrine systems. It is particularly sensitive to various types of stress, which induce its atrophy. This study deals with the effect of repeated restraint stress on the weight, proliferation and apoptosis of the thymus in mice. During restraint, the animals were placed in 50-mL conical plastic tubes for 2 h every day for either 10 or 20 consecutive days. A significant reduction in thymus weight along with decreased cellularity and pronounced atrophy of the cortical part of the thymus was observed in animals exposed to repeated tube-restraint stress for 10 and 20 consecutive days. The observed changes in the thymus were the same, regardless of the number of days of exposure to stress. These findings provide a more comprehensive view of repeated tube-restraint, with special emphasis on its duration on stress-induced thymus atrophy. The presented findings could serve as a basis for further studies aimed at identifying the mechanisms responsible for the adaptive response of the thymus after repeated exposure to stress.

The effects of intracerebroventricularly applied ghrelin on thymocytes and thymic architecture in rats of different ages

Ghrelin positively influences the total number of thymocytes and size of the thymus in 14-, 20- and 24-month-old rats. We examined the effect of centrally-applied ghrelin on thymus weight and structure in Wistar rats of different ages. The study included 30 male Wistar rats of three age groups: peripubertal (5-week-old rats), young (2 months) and adult (6 months). The animals of each age group were divided into control and experimental groups that were administered intracerebroventricularly (ICV) 1 ?g ghrelin/5 ?L saline daily for five consecutive days. Following treatment, the thymuses were isolated, weighed and processed for stereological analysis by the point-counting method. The average weights of the thymuses were significantly higher in the ghrelin groups with respect to control rats (5 weeks: 444.90?18.03 vs 365.00?18.63; 2 months: 354.30?13.77 vs 257.00?9.60; 6 months: 365.00?15.90 vs 225.00?7.03, p<0.01). The absolute volume of lymphoid tissue was significantly higher in the ghrelin groups (5 weeks: 392.85?16.94 vs 294.48?33.37; 2 months: 309.30?12.10 vs 216.62?10.72; 6 months: 222.70?11.41 vs. 114.33?16.48, p<0.01). Ghrelin treatment restored thymic structure by increasing medullary cellularity, improving thymic medullary architecture and providing a clearer delineation between the cortex and medulla. This study shows the positive effects of centrally applied ghrelin on suppression of thymus atrophy, its weight and architecture.

Gender-Related Effect of Sodium Dichloroacetate on the Number of Hassall’s Corpuscles and RNA NKCC1 Expression in Rat Thymus

The aim was to investigate the effect of dichloroacetate (DCA) on thymus weight, Hassall’s corpuscle number (HCs), and NKCC1 RNA expression in Wistar rats aged 4–5 weeks. They were investigated in the controls and DCA-treated gonad-intact and castrated males and females. The treatment lasted 4 weeks with DCA 200 mg/kg/day. At the end of the experiment, rat thymus was weighted, and its lobe was taken for the expression of NKCC1 RNA determined by the PCR method and of Hassall’s corpuscles by immunohistochemistry. DCA caused a thymus weight decrease in DCA-treated gonad-intact rats of both genders as compared with their controls (p < 0.05), and no such impact was found in castrated DCA-treated males and females. DCA caused an increase of the HCs in gonad-intact males (p < 0.05), and no such increase in the DCA-treated gonad-intact females was found. There was gender-related difference in the HCs when comparing DCA-treated gonad-intact males and females: males showed significantly higher HCs (p < 0.05); no gender-related differences were found in the castrated DCA-treated groups. The Slc12a2 gene RNA expression level was found to be significantly decreased only in gonad-intact and in castrated DCA-treated males. The authors discuss the gender-related DCA effects on the thymus.

Evaluation of the effects of autohemotransfusion in arthritic rats induced by two doses of complete Freund´s adjuvant

The aim the study was to evaluate the effects of autohemotransfusion in adjuvant-induced arthritis model by injections of high and low doses of Complete Freund´s Adjuvant (CFA). Male Holtzman rats (200-230g) were distributed in six groups: control (C); control treated by autohemotransfusion (CT); CFA induced arthritis 0.5% w/v (AIA); CFA induced arthritis 0.5% w/v treated with autohemotransfusion (AIAT); CFA induced arthritis 0.1% w/v (AS) and CFA induced arthritis 0.1% w/v treated with autohemotransfusion (AST). The number of leukocytes, the weight of different organs and the paw volume were analyzed. The autohemotransfusion without erythrocytes promoted a reduction in the number of leukocytes in AIAT and AST when compared to AIA (p < 0.001). In the AST group an increase of the thymus weight (p < 0.05) was observed when compared to C, AIA and AIAT. The autohemotransfusion did not prevent the occurrence of paw edema in arthritic animals of AIAT and AST groups (p>0.05). The autohemotransfusion used in this work presented positive effects on AIA as they promoted a reduction in the number of leukocytes and an increase in thymus weight and body growth. However, other types of autohemotransfusion must be tested to determine the true efficacy of this alternative method of treatment.