Vitamin A deficiency potentiates carbon tetrachloride-induced liver fibrosis in rats

Abstract

Earlier studies have shown that retinoid administration suppresses the generation of hepatic fibrosis and stimulates its regression in normal (i.e., vitamin A-sufficient) carbon tetrachloride-treated rats. This study focuses on the possible role of a marginal or deficient vitamin A status on carbon tetrachloride-induced fibrosis. This experimental study in rats shows that vitamin A status, reflected by hepatic retinoid content (retinol and retinyl esters), modulates the development of hepatic fibrosis induced by carbon tetrachloride. In rats with low hepatic retinoid levels (12 +/- 0.9 micrograms/gm liver), carbon tetrachloride-induced liver fibrosis was more pronounced than in rats with sufficient hepatic retinoid levels (1,065 +/- 327 micrograms/gm liver). Enhanced liver fibrogenesis was confirmed both morphologically and by a higher hydroxyproline content of the liver. It was associated with a reduced liver weight and the development of parenchymal regeneration nodules. Furthermore, carbon tetrachloride treatment itself reduced the hepatic retinoid content in rats independently of the liver vitamin A status before treatment and increased serum retinol levels in vitamin A-sufficient rats. The results show that the vitamin A status of the liver plays an important role in hepatic fibrogenesis. Low hepatic vitamin A levels, which can be the result not only of low dietary intake but also of interference with vitamin A metabolism by agents such as ethanol and carbon tetrachloride, may be a risk factor for the development of liver fibrosis. We suggest that retinoids modulate collagen synthesis and deposition irrespective of the degree of hepatocellular necrosis induced by carbon tetrachloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

“…Although loss of retinoid is a prominent feature accompanying stellate cell activation both in vivo (421) and in culture (175), it is unknown whether this process is a prerequisite for activation to occur. The reports about effects of retinoids on stellate cells and fibrogenesis are contradictory (115,116,199,236,423,460,461,563,582,583,588). In culture, both retinol and retinoic acid suppress stellate cell proliferation, and retinoic acid (RA) is 1,000 times more potent than retinol (116).…”

PPARβ regulates vitamin A metabolism-related gene expression in hepatic stellate cells undergoing activation

“…Esterification of retinol might be one of these pathways. VitA deficiency in rats has been shown to potentiate CCl 4 -induced liver fibrosis (18), whereas chronic hypervitaminosis A results in severe liver fibrosis by a poorly understood mechanism (19). The goal of the present study was to analyze the expression of a number of genes involved in FA and retinol uptake and storage during conversion of hepatic stellate cells into their activated phenotype.…”

Protective Role of <i>Commiphora molmol</i> Extract against Liver and Kidney Toxicity Induced by Carbon Tetrachloride in Mice

“…Carbon tetrachloride (CCl 4 ) is a common industrial solvent characterized by its toxic effects on the liver [1]. However, the liver is not the only targeted organ for CCl 4 ; it also affects the kidney as well [2].…”