The Effect of Metformin versus Vitamin E on the Testis of Adult Diabetic Albino Rats: Histological, Biochemical and Immunohistochemistry Study

Background: Impairment of testicular function is one of complications of Diabetes mellitus (D.M) and this may result from increased oxidative stress. Vitamin E (Vit E) has antioxidant properties. Objective: To determine the microscopic changes in the diabetic testis with metformin alone or with Vit E and which of them are better to preserve the testicular structure. Materials and Methods: Fifty adult albino rats, were equally divided into five groups: Group 1: control group;group 2: diabetic group (diabetes was induced by (65 mg/kg;i.p) single dose of streptozotocin (STZ);group 3: vit.E-treated diabetic group (200 mg/kg/day) ip;group 4: Metformin-treated diabetic group (100 mg/kg/day) and group 5 Metformin and vit.E-treated diabetic group for eight weeks. Levels of testosterone, insulin and blood sugar were analyzed and testes specimens were prepared for light microscope and immunohistochemical detection of androgen receptor (AR) and caspase-3. Results: In diabetic group showed irregular seminiferous tubules with depletion, separation, vacuolation of the spermatogenic cells with perivascular and intertubular fibrosis also, the mean diameter of tubules significantly decreases. There are negative immunoexpressions of AR with positive caspase-3. Sections of metformin treated diabetic group showed incomplete or partial regeneration of germ cells while in group 4 and 5 showed almost complete regeneration of spermatogenic cells with increase in mean diameter of tubules, significantly increases in AR and decreases in caspase-3 expression. Conclusion: D.M produce damage in the testicular tissue and the concomitant administration of vit-E with metformin was shown better effect than metformin alone.

Liver angiogenesis: tumor host interaction in non-metastatic colorectal cancer

Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investigate the liver angiogenesis in non-metastatic colorectal cancer (CRC). Methods: Human colorectal adenocarcinoma tumors were grown subcutaneously in nude mice. All animals showed tumor growth locally without macroscopic or microscopic evidence of liver metastases. Livers were investigated for their microvessel density (MVD) at different stages of tumor growth (as small, medium, and large-sized tumors). Normal non-tumor-bearing mice served as controls. To assess MVD, two endothelial cell markers (anti-CD34 and -CD31 antibodies), image analysis, and immunofluorescent technique were utilized. Enumeration of positive stained endothelial cells revealed the MVD. Results: Non-metastatic livers showed increased levels of MVD vs. control. Moreover, levels of MVD were higher in small and medium-sized tumor groups versus large sized tumor groups. Conclusion: The present data indicate that angiogenesis in the liver is induced in early-stages of CRC. However, this effect is suppressed with advanced tumor growth. These results provide an additional rationale for including antiangiogenic therapy in the treatment of early stages of CRC.

Cholesterol Potentiates β-Amyloid Genesis in Cultured Human Umbilical Vein Endothelial Cells

Cerebral Amyloid Angiopathy (CAA) occurs commonly among the elderly and almost invariably in patients with Alzheimer’s Disease (AD). The β-amyloid peptides (Aβ) are produced via the amy-loidogenic processing of β-Amyloid Precursor Protein (APP) by β-secretase-1 (BACE1) and γ- secretase. Vascular endothelial cells are lately shown to possess the molecular machinery of Aβ production, which might participate in the development of CAA. Hypercholesterolemia is considered a risk factor for AD, whereas less is known if cholesterol may modulate endothelial Aβ production. In the present study we verified the amyloidogenic capability of Human Umbilical Vein Endothelial Cells (HUVECs) in vitro and explored the effect of cholesterol exposure on their amy-loidogenic potential. Cholesterol treatments at 12.5 and 25 mg/dL significantly elevated APP, BACE1 and APP β-CTF protein levels and β-site APP cleavage activity in cell lysates, and Aβ40 levels in culture medium. However, coincubation with cholesterol at 50 and 100 mg/dL attenuated the viability of the cultured cells and diminished their amyloidogenic capability. These findings suggest that high cholesterol exposure is stressful to vascular endothelial cells, and at a certain dosage range can promote an amyloidogenic response in these cells.