Mohamed H. Mansour

Cyto-protective and immunomodulating effect of Curcuma longa in Wistar rats subjected to carbon tetrachloride-induced oxidative stress

Abstract.A comparison of crude curcuminoid extract and purified curcumin was made to evaluate hepato- and immunoprotective effect of Curcuma longa (turmeric) Zingiberaceae. Carbon tetrachloride (CCl4) induced cellular hepatic damage was evaluated by transmission electron microscopy, hepatic enzymes and thiobarbituric acid reactive species (TBAR) values. A selective cytolytic effect of CCl4 was observed among immature (PNA+) thymocytes and peripheral helper (CD4+) T lymphocytes in spleen and was paralleled by a significant reduction in CD25, CD71 and Con A receptor expression. Treatment with curcuminoid crude extract at two different doses, showed a significant cellular recovery among hepatocytes, which was reflected in a reduction of hepatic enzymes and TBAR values. A significant restoration of lymphocyte viability and CD25, CD71 and Con A receptor expression in both immature (PNA+) thymocytes and splenic helper (CD4+) T lymphocytes was observed. Turmeric crude extract, at both low and high dose, was found to be more efficient as compared to purified curcumin.

Green Tea Attenuates Oxidative Stress and Downregulates the Expression of Angiotensin II AT1 Receptor in Renal and Hepatic Tissues of Streptozotocin-Induced Diabetic Rats

This study investigates the potential of green tea to modulate oxidative stress and angiotensin II AT1 receptor expression in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (diabetic control), and green-tea-treated diabetic rats. Total antioxidant, catalase, and malondialdehyde levels were assayed by standard procedures. Levels of AT1 receptor labeling, in renal and hepatic tissues of the three rat groups, were immunohistochemically investigated using an anti-AT1 receptor antibody. Levels of total antioxidant and catalase were significantly reduced, whereas malondialdehyde levels and AT1 receptor labeling were significantly increased in renal and hepatic tissues of diabetic control rats compared to normal rats. Compared to diabetic control rats, total antioxidant and catalase levels were significantly increased, whereas malondialdehyde levels and AT1 receptor labeling in the green-tea-treated diabetic group were significantly reduced throughout hepatic lobules and renal cortical and medullary vascular and tubular segments to levels comparable to those observed in normal rats. The capacity of green tea to modulate diabetes-induced oxidative stress and AT1 receptor upregulation may be beneficial in opposing the deleterious effects of excessive angiotensin II signaling, manifested by progressive renal and hepatic tissue damage.

Garlic decreases liver and kidney receptor for advanced glycation end products expression in experimental diabetes.

The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy and hepatic fibrogenesis. The present study was designed to investigate the potential of garlic (Allium sativum L.) to modulate the level of expression of RAGE in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal and hepatic tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in glomeruli exhibiting signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In the liver, a significant up-regulation of RAGE was observed in hepatocytes and bile ducts and vessels in portal tracts. In 2-dimensional Western blots, RAGE expression in both tissues was dominated by heterogeneous charge variants, represented by 46-50kDa isoforms with more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal and hepatic regions and was marked by the expression of 43-50kDa acidic charge variants comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders.

Garlic (Allium sativum) attenuate glomerular glycation in streptozotocin-induced diabetic rats: A possible role of insulin

OBJECTIVE This study investigated the effect of fresh garlic aqueous extract on glomerular glycation in streptozotocin-induced diabetic rats. METHOD Serum insulin and glucose, in addition to renal corpuscles and erythrocyte hemoglobin glycation were determined in normal saline-treated normal rats (NS-NR), normal saline-treated diabetic rats (NS-DR) and garlic-treated diabetic rats (G-DR). RESULTS Compared to NS-NR, NS-DR showed significant decrease in serum insulin and increase in serum glucose and hemoglobin glycation. NS-DR also showed intense, diffused glomerular periodic acid Schiff activity. Compared to NS-DR, G-DR showed significant increase in serum insulin and decrease in serum glucose and hemoglobin glycation. Furthermore, the G-DR glomerular periodic acid Schiff activity and distribution was almost restored to that observed in NS-NR. CONCLUSION Garlic may attenuate glomerular glycation in streptozotocin-induced diabetic rats. This effect could be partially mediated via euglycemia induced by revitalization of endogenous insulin.

Age-related structural modulation of T lymphocyte-associated CD45 isoforms.

A monoclonal antibody, specific to all conventional CD45 isoforms, was employed in two-dimensional (2D) sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting to investigate possible age-related differential expression of these isoforms among immature and mature thymocytes as well as CD4+ and CD8+ T cell subpopulations in the periphery of newly-born, young and aged BALB/c mice. In young mice, and to a lesser degree in newly-born mice, intra-thymic maturation seemed to be paralleled by the capacity of thymocytes to synthesize distinct CD45 isoforms constituted by extensively heterogeneous acidic charge entities. Thymocyte maturation in aged mice, on the other hand, was characterized by minimal heterogeneity, as the observed pattern was essentially similar to the immature population in 2D blots. As inferred from comparisons of 2D blots of sialylated and desialylated forms of the CD45 complex, age-related differences in isoforms expressed by the CD4+ and the CD8+ T cell subpopulations in the periphery resided mainly in the degree of sialylation of the constituent isoforms. Given the potential of the differential sialylation state of CD45 in altering the recognition properties of lymphocytes, regulation of CD45 sialylation with age may add another level of complexity to the lymphocyte surface phenotype, which in turn may be implicated in cell-cell interaction mechanisms during lymphocyte maturation and senescence.

Identification and localization of a schistosome-associated fucosyllactose determinant expressed by Fasciola hepatica

A Biomphalaria alexandrina-derived lectin (BaSII), of proven specificity to a Schistosoma mansoni-associated fucosyllactose [(Fuc alpha1-2) Gal beta1-4 Glc] determinant, was employed to investigate the putative antigenic cross-reactivity between Schistosoma mansoni and Fasciola hepatica in terms of this structurally-defined oligosaccharide sequence. BaSII affinity column chromatography of extracts of adult worms metabolically radiolabelled with 35S-methionine and analysis by two-dimensional gels established the expression of the fucosyllactose determinant in multiple copies among heterogeneous, acidic glycoproteins synthesized by adult Fasciola hepatica. Direct fluorescence microscopy revealed that determinant-bearing glycoproteins were localized to the external glycocalyx and perikarya of the tegument as well as the epithelial lining of the intestinal caeca and vitelline ducts and glands. Determinant expression was also evident in embryonated cells of eggs and miracidia as well as the intermediate cellular wall of encysted metacercariae, suggesting its conservation during the course of development of the parasite. Based on the structural relatedness of the cross-reactive fucosyllactose determinant to the antigenic mammalian blood group H trisaccharide, our observations may have implications in serodiagnosis and immunoprophylaxis of schistosomiasis/fascioliasis.

Curcuma longa attenuates carbon tetrachloride-induced oxidative stress in T-lymphocyte subpopulations.

A comparison of crude curcuminoid extract and purified curcumin was made to evaluate the immunoprotective effect of Curcuma longa (turmeric) Zingiberaceae. Carbon tetrachloride (CCl4) induced selective cytolytic effects among immature (PNA(+)) thymocytes and peripheral helper (CD4(+)) T lymphocytes in the spleen were paralleled by a significant reduction in CD25, CD71, and Con A receptor expression. Treatment with curcumanoid crude extract, at two different doses, showed a significant restoration of lymphocyte viability and CD25, CD71, and Con A receptor expression in both immature (PNA+) thymocytes and splenic helper (CD4(+)) T lymphocytes. Turmeric crude extract, at both low and high dose, was found to be more efficient as compared to purified curcumin, suggesting synergistic effect of curcumin with other components of the crude extract.

Characterization of fucose-binding lectins in rock-and mud-dwelling snails inhabiting Kuwait Bay

Two novel lectins that bind selectively to trematode-associated fucosylated determinants have been characterized and purified from the hemolymph of wild-type rock-dwelling Turbo coronatus and mud-dwelling Cerithidea cingulata snails inhabiting Kuwait Bay. Both lectins were separately purified from the hemolymph of T. coronatus (designated Tc lectin) and C. cingulata (designated Cc lectin) by affinity chromatography on immobilized L-fucose-agarose columns and elution with a gradient of 0.1-1 M L-fucose. Assessments of the structural characteristics, by one- and two-dimensional polyacrylamide gel electrophoresis, indicated that Tc and Cc lectins were structurally distinct, and exist in their native forms as multimers of non-covalently associated subunits of different sizes and pIs. Removal of N-linked glycans by endo-beta-N-acetylglucosaminidase F resolved the heterodisperse pattern of Tc lectin subunits into 31 and 27 kDa components (each with a pI of 7.8) as well as an 8 kDa component with a pI of 7.2, and collapsed the size microheterogeneity of the Cc lectin subunits into a single spot of 33 kDa (pI 5.4). Each of these subunits is subjected to differential post-translational N-linked glycosylations, which involve variable acidic complex-type units in Tc lectin and neutral high-mannose-type units in Cc lectin. Based on trematode glycoprotein binding and inhibition assays, the two lectins exhibited optimum binding at a similar pH range, but were distinct in terms of their temperature stability as well as binding affinities towards the fucose moiety constituting the fucosylated target.