Liver Fibrosis

Rojkind, Marcos; Pérez-Tamayo, Ruy

doi:10.1016/b978-0-12-363710-9.50012-5

Cited by 64 publications

(37 citation statements)

References 237 publications

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“…44 DMN is toxic to hepatocytes and could induce coagulation necrosis, predominantly in the central and periportal regions of the lobule. 45 Products of inflammatory cells, such as transforming growth factor ␤ 1 , may augment the fibrogenic response by targeting HSC.…”

Section: Discussionmentioning

confidence: 99%

Suppressive Effects of Estradiol on Dimethylnitrosamine–Induced Fibrosis of the Liver in Rats

et al. 1999

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As a model for the analysis of the fibrosuppressive role of estradiol, hepatic fibrosis was induced in male and female rats by the administration of a single dose of dimethylnitrosamine (DMN). The fibrotic response of the male liver after DMN treatment was significantly stronger than that of the female liver. In the male DMN model, estradiol reduced hepatic mRNA for type I and III procollagens and the tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as deposition of type I and III collagen protein total hepatic collagen and malondialdehyde (MDA), a product of lipid peroxidation. Concomitant administration of a neutralizing antibody against rat estradiol enhanced fibrogenesis, as judged by the same parameters. Ovariectomy in the female model had a fibrogenic effect, inducing the hepatic expression of both types of procollagen and TIMP-1; in addition, the number of ␣-smooth muscle actin (␣-SMA)-positive cells in the liver increased; estradiol replacement was fibrosuppressive in the castrated-female model. In rat hepatic stellate cells incubated in primary culture with estradiol, cell number, type I collagen production, and ␣-SMA expression were all reduced. These findings suggest that estradiol suppressed the induction of hepatic fibrosis, and may in part underlie the more rapid progression in males of hepatic fibrosis and its complications. (HEPATOLOGY 1999;29:719-727.)Hepatic fibrosis is a consequence of severe liver damage and, in many chronic liver diseases, progresses to cirrhosis. 1,2 It consists of an abnormal accumulation of extracellular matrix proteins, particularly collagens. 3 Hepatocellular carcinoma is strongly associated with cirrhosis. 4 Among patients with cirrhosis and hepatocellular carcinoma, the male:female ratio is in the range of 2.3:1 to 2.6:1. 5,6 Both male and female livers contain high-affinity, low-capacity estrogen receptors 7,8 and respond to estrogens by regulating liver function. 9,10 This suggests that sex hormones may play a role in the progression from hepatic fibrosis to cirrhosis.It is now evident that hepatic stellate cells (HSC) (Ito cells, fat-storing cells, lipocytes) in the space of Disse undergo transformation under inflammatory stimuli into ␣-smooth muscle actin (␣-SMA)-positive myofibroblast-like cells, and are responsible for much of the collagen hypersecretion and nodule formation that occurs during hepatic fibrosis and cirrhosis. 11,12 Our preliminary studies suggested that fibrotic liver-collagen levels initially increase partly as a result of the balance between type I collagen and matrix metalloproteinase-1 (MMP-1) expression rates during the course of hepatic fibrosis in rats, as induced by a single dose of dimethylnitrosamine (DMN), 13 and that estradiol inhibits the myofibroblastic transformation of rat HSC in primary culture. 14 It is also noteworthy that oxygen-derived free radicals and lipid peroxidation have been implicated in hepatic fibrosis. 15-17 HSC may be activated by free radicals, induced by ascorbate/FeSO 4 , as well as by malondialdehyde ...

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Section: Discussionmentioning

confidence: 99%

Suppressive Effects of Estradiol on Dimethylnitrosamine–Induced Fibrosis of the Liver in Rats

et al. 1999

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“…45 Stellate cells are regarded as the primary target cells for inflammatory stimuli in the injured liver. 46 When activated, stellate cells are transformed into myofibroblast-like cells, which lose cellular retinoid and synthesize large amounts of ␣-SMA and the major components of the ECM.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sho–Saiko–To, A Japanese Herbal Medicine, on Hepatic Fibrosis in Rats

Shimizu¹,

Ma²,

Mizobuchi³

et al. 1999

Hepatology

226

189

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It has been shown that lipid peroxidation is associated with hepatic fibrosis and stellate cell activation. Shosaiko-to (TJ-9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the mechanism by which TJ-9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ-9 on experimental hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pig serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ-9. Male Wistar rats were given a single intraperitoneal injection of 40 mg/kg DMN or 0.5 mL PS twice weekly for 10 weeks. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ-9, for 2 weeks before treatment or for the last 2 weeks of treatment. TJ-9 suppressed the induction of hepatic fibrosis, increased hepatic retinoids, and reduced the hepatic levels of collagen and malondialdehyde (MDA), a production of lipid peroxidation. Immunohistochemical examination showed that TJ-9 reduced the deposition of type I collagen and the number of ␣-smooth muscle actin (␣-SMA) positive-stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoing oxidative stress, but also the production of type I collagen, ␣-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition, TJ-9 inhibited Fe 2؉ /adenosine 5Ј-diphosphate-induced lipid peroxidation in rat liver mitochondria in a dose-dependent manner and showed radical scavenging activity. Among the active components of TJ-9, baicalin and baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocytes and stellate cells in vivo. (HEPATOLOGY 1999;29:149-160)

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“…In animals with advanced cirrhosis, a critical upper limit of collagen concentration is reached, and the loss of the normal Type I/Type 111 ratio becomes apparent (82).…”

Section: Collagen Typesmentioning

confidence: 99%

Is Cirrhosis of the Liver Experimentally Produced by Cc14 An Adequate Model of Human Cirrhosis?

Tamayo

1983

Hepatology

282

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Liver Fibrosis

Cited by 64 publications

References 237 publications

Suppressive Effects of Estradiol on Dimethylnitrosamine–Induced Fibrosis of the Liver in Rats

Suppressive Effects of Estradiol on Dimethylnitrosamine–Induced Fibrosis of the Liver in Rats

Effects of Sho–Saiko–To, A Japanese Herbal Medicine, on Hepatic Fibrosis in Rats

Is Cirrhosis of the Liver Experimentally Produced by Cc14 An Adequate Model of Human Cirrhosis?

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