The impact of busulfan on the testicular structure in prepubertal rats: A histological, ultrastructural and immunohistochemical study.

Busulfan is a widely used cancer chemotherapeutic agent. Temporary or permanent sterility in male patients is one of the most common side effects of this drug. The present study was performed to evaluate the changes in the microscopic structure of the testes of prepubertal rats, as well as the changes in PCNA and caspase-3 immune expression, at different durations after busulfan administration. The rats were 5 weeks old and were divided into two main groups. Control group and busulfan treated group. Busulfan treated group received a single dose of busulfan (40 mg/kg), then animals were subdivided to three subgroups; IIa, IIb, IIc which were sacrificed after four, ten and twenty weeks, respectively, from the beginning of the experiment. Light and electron microscopic studies were done. Serum testosterone level and relative testes weight were assessed. Immunohistochemical staining for anti-proliferating cell nuclear antigen (PCNA) and anti-caspase-3 antigen was also done. Morphometric and statistical studies were carried out. Group II revealed histological and ultrastructural degenerative changes including congested blood vessels and degenerated spermatogenic epithelium, Sertoli cells, and Leydig cells. These changes were more evident after 10 weeks of busulfan administration and were accompanied by absence of mature sperms in the lumen of seminiferous tubules. These changes were associated with a significant reduction in relative testes weight, testosterone level, germinal epithelial height and seminiferous tubule diameter. Moreover, PCNA and caspase-3 immune expression was significantly altered in busulfan treated group. Mild improvement in testicular structure was observed 20 weeks after busulfan treatment.

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.

Characterization and anti-aging effects of Opuntia ficus-indica (L.) Miller extracts in a D-galactose-induced skin aging model.

Opuntia ficus-indica (L.) Miller (OFI), belonging to the family Cactaceae, is widely cultivated not only for its delicious fruits but also for its health-promoting effects, which enhance the role of OFI as a potential functional food. In this study, the in vitro collagenase and elastase enzyme inhibitory effects of extracts from different parts of OFI were evaluated. The most promising extracts were formulated as creams at two concentrations (3 and 5%) to investigate their effects on a D-galactose (D-gal)-induced skin-aging mouse model. The ethanolic extracts of the peel and cladodes exhibited the highest enzyme inhibitory effects. Cream made from the extract of OFI peel (OP) (5%) and cream from OFI cladodes extract (OC) (5%) significantly decreased the macroscopic aging of skin scores. Only a higher concentration (5%) of OC showed the normalization of superoxide dismutase (SOD) and malondialdehyde (MDA) skin levels and achieved significant improvements as compared to the vitamin E group. Both OC and OP (5%) showed complete restoration of the normal skin structure and nearly normal collagen fibres upon histopathological examination. The Ultra-Performance Liquid Chromatography High Resolution Mass Spectrometry (UHPLC-ESI-TOF-MS) metabolite profiles revealed the presence of organic acids, phenolic acids, flavonoids, betalains, and fatty acids. Flavonoids were the predominant phytochemical class (23 and 22 compounds), followed by phenolic acids (14 and 17 compounds) in the ethanolic extracts from the peel and cladodes, respectively. The anti-skin-aging effects could be attributed to the synergism of different phytochemicals in both extracts. From these findings, the OFI peel and cladodes as agro-waste products are good candidates for anti-skin-aging phytocosmetics.

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

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.

Potential role for vitamin D vs. intermittent fasting in controlling aquaporin-1 and aquaporin-3 expression in HFD-induced urinary bladder alterations in rats.

Background: High-fat diet-induced obesity is linked to suppression of aquaporins (AQPs) expression in different tissues. Both vitamin D and intermittent fasting were identified to enhance AQPs expression. In the urinary bladder, AQP-1 and AQP-3 mRNA transcripts were identified. Vitamin D has an impact on a variety of genes that encode proteins that control cell proliferation, differentiation, and death. Aim: To assess potential benefits of vitamin D and intermittent fasting (IF) and to explore alterations to the urinary bladder triggered by high-fat diet (HFD) in a rat model of obesity. Methods: Each of the 4 groups contained six adult male albino rats; control: a standard rodent chew for 12 weeks, HFD: HFD and fructose were administered orally via gastric gavage for 12 weeks, and vitamin D: HFD and fructose were administered orally for 8 weeks, then 4 weeks of intraperitoneal injection of vitamin D (5 microns/Kg/2 days) and IF group: Received intraperitoneal injections of vitamin D (5 microns/Kg/2 days) for 4 weeks after consumption of HFD and fructose orally for 8 weeks. The serum lipid profile was conducted at end of the experiment. In the bladder homogenates, the levels of oxidative stress indicators were assessed. Quantitative real-time PCR was performed on recently collected bladder samples. AQP-1 and AQP-3 immunohistochemistry was done. Results: When compared to the HFD group, the vitamin D and IF groups both demonstrated a substantial improvement in histopathological, immunohistochemical, biochemical, and molecular markers. Conclusion: In all examined parameters, IF exceeded vitamin D as a preventive factor for the urinary bladder deterioration.

Identification of the Molecular Basis of Nanocurcumin-Induced Telocyte Preservation within the Colon of Ulcerative Colitis Rat Model.

BACKGROUND: Telocytes (TCs) are a distinct type of interstitial cells that play a vital role in the pathogenesis of ulcerative colitis and colonic tissue hemostasis. The aim of this study was to examine the effect of nanocurcumin (NC) on the morphometric and immunohistochemical characterization of TCs in the ulcerative colitis (UC) rat model. METHODS: Forty rats were randomly divided into control, NC, UC, and UC+NC groups. At the end of the experiment, the colon was dissected and prepared for histopathological and immunohistochemical assessment. Tissue homogenates were prepared for real-time PCR assessment of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß) gene expression. Our results revealed extensive mucosal damage with inflammatory cell infiltration, significant reduction of CD34, and vimentin immunostained TCs in the colon of the UC group with significant elevation of expression of IL-6, TNF-α, and TGF-ß. The UC+NC-treated group revealed significant elevation of TC count compared to the UC group besides, a significant reduction of the three gene expression. CONCLUSION: NC successfully targeted the colonic tissue, improved the mucosal lesion, preserve TCs distribution, and count through its anti-inflammatory and fibrinolytic properties.

p53 Rather Than ß-Catenin Mediated the Combined Hypoglycemic Effect of Cinnamomum cassia (L.) and Zingiber officinale Roscoe in the Streptozotocin-Induced Diabetic Model.

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now. Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger (Zingiber officinale Roscoe) and cinnamon (Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect. Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague-Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA-ß cells were performed. Pancreatic gene expression of ß-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques. Results: BGL significantly decreased (p = 0.01), while serum insulin and TAC significantly increased (p < 0.001) in both metformin- and ginger plus cinnamon-treated groups compared to the untreated diabetic group. HOMA-ß cell index significantly increased (p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated (p < 0.001), while ß-catenin was insignificantly downregulated (p = 0.32) in ginger plus cinnamon-treated groups. Insulin immunoexpression in ß cells significantly increased (p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon-treated groups, respectively. Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.