Ultrastructural and immunohistochemical study of ITO cells of rat in carbon tetrachloride -induced liver fibrosis and the protective effect of vitamin A

The hepatic stellate cells, Ito cells, were known to play multiple roles in liver histopathology. This study was undertaken to explore the role of these cells in carbon tetrachloride [CCL4]- induced liver fibrosis, histologically and immunohistochemically, and to investigate the protective effect of vitamin A. Fifty rats were used and divided into three groups. The first group served as a control. The rats of the second group were injected twice a week with CCL4 for eight weeks, while the animals of the third group were pretreated with Vitamin A before injection of CCL4. At the end of each experiment, specimens from the liver of the animals were taken and processed for transmission EM study and immunohistochemical demonstration of GGaI fibrillary acidic protein [GFAP] and alpha smooth muscle actin [alphaSMA]. Eight weeks after CCL4 administration, thick and irregular C.T. septa with formation of definite lobules and pseudolobules were detected. GFAP-positive to cells were few in number intralobularly and in the C. T. septa. In contrast, there were numerous alphaSMA-positive cells. However, in Vitamin A-pretreated rats numerous GFAP-positive ito cells and few alphaSMA-positive cells were detected in-side the lobules. Ultrastructurally, three types of Ito cells were detected in the liver of CCL4-intoxicated rats. Some Ito cells resembled myofibroblasts, others contained many lipid droplets and activated rER, while septal Ito cells attained a fibroblast like feature. On the contrary, in Vitamin A pretreated group, Ito cells contained numerous lipid droplets and had few dilated rER cisternae. From this current study, we that immunohistochemical demonstration of GFAP and alphaSMA may be alpha method for studying hepatic fibrogenesis. Moreover, it is recommended that, Vitamin A may have a protective effect against carbon tetrachloride-induced hepatotoxicity

Up regulation of angiogenic growth factors is associated with renal dysfunction in type 2 diabetes mellitus

TYPE 2 diabetes mellitus has reached epidemic proportions, and one of its ominous complications, diabetic nephropathy [DN], represents today the leading cause of end-stage renal failure [ESRF]. A large amount of evidence supports the hypothesis that a panel of growth factors, are involved in the development of diabetic nephropathy through a complex intra renal system. This study was applied to study the changes in the blood levels of transforming growth factor-beta [TGF-beta], vascular endothelial growth factor [VEGF], and basic fibroblast growth factor [bFGF] in diabetic patients with and without nephropathy, and to investigate whether they were associated with renal impairment. Such information is crucial to determining the optimal approach to the treatment and prevention of the disease

Methods: 51 subjects were enrolled in the study, and were divided into three groups; the first group consisted of 12 healthy subjects; the second of 17 patients with type 2 diabetes without nephropathy [normoalbuminuric]; and the third group of 22 patients with type 2 diabetic nephropathy [macroalbuminuric]. Growth factors determination was performed using enzyme-linked immunosorbent assay [ELISA]

Results: Serum TGF-beta and bFGF values showed significant elevation in both diabetic groups as compared to healthy subjects [P<0.001], with insignificant difference between both diseased groups. Serum VEGF levels, on the other hand, were significantly elevated in patients with DN as compared to both healthy subjects and diabetics without renal impairment [P<0.001]. Serum VEGF showed significant direct correlation with serum creatinine [r= 0.490, P= 0.006], serum urea [r= 0.537, P= 0.0004], and serum bFGF [r=0.372, P=0.02]. Significant direct correlation was also recorded between serum TGF-beta and both serum creatinine [r=0.401, P=0.011], and serum VEGF [r=0.341, P=0.034]

Conclusions: Our results support the hypothesis that a network of growth factors may participate in the development of renal functional impairment in patients with type 2 diabetes. Further insight into the complex processes that regulate this network may be useful in the future development of new antagonists useful in the treatment of diabetic Kidney disease