Previous studies suggested a relation between oxidative stress and collagen hyperproduction. Carbon tetrachloride-induced hepatic fibrosis has been considered to be mediated by aldehydic lipid peroxidation products. In the present study we investigated whether collagen synthesis is induced by F2-isoprostanes, the most proximal products of lipid peroxidation and known mediators of important biological effects. By contrast with aldehydes, F2-isoprostanes act through receptors able to elicit definite signal transduction pathways. In a rat model of carbon tetrachloride-induced hepatic fibrosis, plasma F2-isoprostanes were markedly elevated for the entire experimental period; hepatic collagen content also increased. When hepatic stellate cells from normal liver were cultured up to activation (expression of -SMA) with F2-isoprostanes in the concentration range found in the in vivo studies (10-9 to 10-8M), a striking increase in DNA synthesis, in cell proliferation and in collagen synthesis was observed. Total collagen content was similarly increased. All these stimulatory effects were reversed by the specific antagonist of thromboxane A2 receptor, SQ29548. Moreover, F2-isoprostanes markedly increased the production of transforming growth factor-1 by U937 cells, considered a model of liver macrophages. The data provide evidence for the possibility that F2-isoprostanes generated by lipid peroxidation in hepatocytes mediate hepatic stellate cell proliferation and collagen hyperproduction seen in hepatic fibrosis.

Gardi, C., Arezzini, B., Signorini, C., Vecchio, D., Monaco, B., Comporti, M. (2008). F2-Isoprostanes markers and mediators of an imbalanced redox status in the liver. In Oxidants in biology: a Question of Balance (pp. 315-324). Berlin : Springer Science [10.1007/978-1-4020-8399-0_17].

F2-Isoprostanes markers and mediators of an imbalanced redox status in the liver

GARDI, C.;AREZZINI, B.;SIGNORINI, C.;VECCHIO, D.;MONACO, B.;COMPORTI, M.
2008-01-01

Abstract

Previous studies suggested a relation between oxidative stress and collagen hyperproduction. Carbon tetrachloride-induced hepatic fibrosis has been considered to be mediated by aldehydic lipid peroxidation products. In the present study we investigated whether collagen synthesis is induced by F2-isoprostanes, the most proximal products of lipid peroxidation and known mediators of important biological effects. By contrast with aldehydes, F2-isoprostanes act through receptors able to elicit definite signal transduction pathways. In a rat model of carbon tetrachloride-induced hepatic fibrosis, plasma F2-isoprostanes were markedly elevated for the entire experimental period; hepatic collagen content also increased. When hepatic stellate cells from normal liver were cultured up to activation (expression of -SMA) with F2-isoprostanes in the concentration range found in the in vivo studies (10-9 to 10-8M), a striking increase in DNA synthesis, in cell proliferation and in collagen synthesis was observed. Total collagen content was similarly increased. All these stimulatory effects were reversed by the specific antagonist of thromboxane A2 receptor, SQ29548. Moreover, F2-isoprostanes markedly increased the production of transforming growth factor-1 by U937 cells, considered a model of liver macrophages. The data provide evidence for the possibility that F2-isoprostanes generated by lipid peroxidation in hepatocytes mediate hepatic stellate cell proliferation and collagen hyperproduction seen in hepatic fibrosis.
9781402083983
Gardi, C., Arezzini, B., Signorini, C., Vecchio, D., Monaco, B., Comporti, M. (2008). F2-Isoprostanes markers and mediators of an imbalanced redox status in the liver. In Oxidants in biology: a Question of Balance (pp. 315-324). Berlin : Springer Science [10.1007/978-1-4020-8399-0_17].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/21328
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