Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats

Abstract

A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr. The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury.

Protective Effect of <b><i>Zingiber Officinale</i></b> against CCl₄-Induced Liver Fibrosis Is Mediated through Downregulating the TGF-ß1/Smad3 and NF-&#954;B/I&#954;B Pathways

“…On the other hand, either the low or the high dose of ginger markedly inhibited this elevation. Ginger is shown to inhibit the enzymes required for synthesis of prostaglandins and leukotrienes, namely, cyclooxygenase and lipoxygenase respectively [25]. The GE is shown to inhibit the release of TNF-α from lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells [26].…”

The anti-fibrotic effect of green tea with a high catechin content in the galactosamine-injured rat liver

“…Immunohistochemical examination revealed increased deposition of extracellular matrix components including collagen type 1 in areas with liver cell necrosis and along sinusoids of the galactosamine-injured rat liver (11). Their immunoreactivities reached a maximum at 36-48 h and decreased to the preinjection level 3 weeks after the injection of galactosamine (11).…”

“…Galactosamine is known to induce hepatic injury in rats that is similar in pathophysiology to viral hepatitis and drug-induced hepatitis in humans (11,14). Hepatic fibrosis is a common response to chronic liver injury from many causes including alcohol and viral infection (6).…”

Hepatoprotective Effects of Whey Protein onD-Galactosamine-Induced Hepatitis and Liver Fibrosis in Rats

“…10,11) The mechanism underlying the hepatotoxic action of GalN has been studied extensively. 12,13) Within 30 min of GalN administration in rats, there is a large accumulation of UDPGalN derivatives in the liver, leading to depletion of hepatic UTP.…”