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In the last years, reactive oxygen species (ROS) have been proposed as mediators of proliferative/hypertrophic responses to angiotensin II (Ang II), both in vivo and in vitro. However, the hypothesis that the Ang II-dependent cell contraction could be mediated by ROS, particularly H2O2, has not been tested. Present experiments were devoted to test this hypothesis and to analyze the possible mechanisms involved. Catalase (CAT) prevented the increased myosin light chain phosphorylation and the decreased planar cell surface area (PCSA) induced by 1 microM Ang II in cultured rat vascular smooth muscle cells (VSMC). This preventive effect of CAT was also detected when 1 microM platelet-activating factor (PAF) was used as a contractile agonist instead of Ang II. Similar results were found when using horseradish peroxidase as an H2O2 scavenger or cultured rat mesangial cells. In vascular smooth muscle cells, CAT modified neither the binding of labeled Ang II nor the Ang II-induced inositol 1,4,5-trisphosphate (IP3) synthesis. However, it completely abolished the Ang II-dependent calcium peak, in a dose-dependent fashion. CAT-loaded cells (increased intracellular CAT concentration over 3-fold) did not show either a decreased PCSA or an increased intracellular calcium concentration after Ang II treatment. Ang II stimulated the H2O2 synthesis by cultured cells, and the presence of CAT in the extracellular compartment significantly diminished the Ang II-dependent increased intracellular H2O2 concentration. The physiological importance of these findings was tested in rat thoracic aortic rings: CAT prevented the contraction elicited by Ang II. In summary, present experiments point to H2O2 as a critical intracellular metabolite in the regulation of cell contraction.

Our results suggest that the acute decrease in glomerular filtration rate induced by CsA might be mediated by the synthesis of reactive oxygen species and subsequent peroxidation of lipids, which increases the levels of TXB2. Treatment with Vit E prevented these effects, suggesting a possible role for antioxidants in the prevention of CsA nephrotoxicity.

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Cytokines make up a network of molecules involved in the regulation of immune response and organ functional homeostasis. Cytokines coordinate both physiological and pathological processes occurring in the liver during viral infection, including infection control, inflammation, regeneration, and fibrosis. Hepatitis B and hepatitis C viruses interfere with the complex cytokine network brought about by the immune system and liver cells in order to prevent an effective immune response, capable of viral control. This situation leads to intrahepatic sequestration of nonspecific inflammatory infiltrates that release proinflammatory cytokines, which in turn favor chronic inflammation and fibrosis. The therapeutical administration of cytokines such as interferon alpha may result in viral clearance during persistent infection, and revert this process.Key words: Cytokines. Chronic hepatitis. HBV. HCV. Immunopathogenesis. INTRODUCTIONCytokines are small soluble proteins secreted by immune system cells and other body cells, and are part of an intercellular communication system responsible for developmental regulation, tissue repair, and immune response in pluricellular organisms (1). These proteins play their role in an autocrine or paracrine manner by binding specific cell receptors that either induce or inhibit cytokine-regulated genes. Over 100 different cytokines have been reported, which are classified according to their primary role (Table I). These proteins are involved in all immune response aspects, and play a key role in immune response polarization and regulation. The combination of cytokines resulting from a specific antigenic stimulus determines the kind of immune response that will develop.During viral infection various cytokines play a role both in viral clearance and tissue damage mechanisms. Viruses may interfere with the normal function of this complex cytokine network as an escape route to avoid destruction.Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic, non-cytopathic viruses of the hepadnavirus and flavivirus families, respectively, that induce both acute and chronic necro-inflammatory liver disease (2,3). HBV escapes immune control in 10% of adult infections, whereas HCV successfully evades the immune system in 60-80% of cases. Changes in various cytokine activities have been reported for both viral infections, which might favor viral persistence.