Mast Cell Density, Hepatic Stellate Cell Activation and TGF-β1 Transcripts in the Aging Sprague-Dawley Rat During Early Acute Liver Injury

Abstract

Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2-and 19-month old rats treated with carbon tetrachloride (CCl 4 ) to assess the relationships between MC density, hepatocellular damage, mRNA encoding TGF-β 1 , hepatic stellate cell (HSC) activation and collagen levels. Consecutive histological sections from each age group were stained with toluidine blue to identify granulated MCs, Direct Red 80 to recognize collagen matrix, and by immunohistochemistry to identify activated hepatic stellate cells (HSCs), which were subsequently counted by means of a computer-aided image analysis. Histology showed hepatocellular necrosis with inflammatory cell infiltration and collagen matrix deposition. Two and 24 hours after intoxication, MC density had considerably increased in the younger rats, but less in those aged 19 months. Although the untreated older rats had a larger area occupied by activated HSCs than the untreated younger rats, the increase in the number of HSCs was greater in the younger rats both two and 24 hours after intoxication. The greater MC density in younger rats suggests that older rats have a reduced immune response or recruit fewer MCs. The activated HSCs and TGF-β 1 transcripts did not increase significantly during the study period, thus indicating that these are later events in chemically induced hepatic toxicity. In conclusion, MC density may be an index of acute liver inflammation after CCl 4 intoxication.

The hepatoprotective effects of dihydromyrcenol and geranyl formate in an experimental model of acute hepatic injury induced by the use of carbon tetrachloride

“…Additionally, changes involving fat were in the form of a few drops of variable size to diffuse involvement (32). After 24 hours, the same characteristic findings were reported to be more severe (32). In our study, histopathological and biochemical changes were observed in the rats exposed to CCl 4 , which were compatible with the results of earlier studies.…”

“…In that particular study, in the hepatocytes located near the centrilobular zone, hydropic degeneration, vacuolization and swelling were observed (32). Additionally, changes involving fat were in the form of a few drops of variable size to diffuse involvement (32). After 24 hours, the same characteristic findings were reported to be more severe (32).…”

“…In the study of Grizzi et al (32), in which the rats were treated with CCl 4 , the authors determined hepatocyte necrosis in the centrilobular zone and inflammatory cell infiltration with high macrophage and lymphocyte concentration 2 hours after the application of CCl 4 . In that particular study, in the hepatocytes located near the centrilobular zone, hydropic degeneration, vacuolization and swelling were observed (32). Additionally, changes involving fat were in the form of a few drops of variable size to diffuse involvement (32).…”

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

“…However, the metabolic perturbation in the DG/CCl 4 group at the 1st and 4th day post-dose of CCl 4 appeared less significant than those in the CCl 4 group. We selected the different expressed metabolites in the rats of CCl 4 group relative to NC group at the 1st day (P1) post CCl 4 exposure, a key time point of liver injury study, and evaluated their variances at different time points of the DG/CCl 4 group (Grizzi et al 2003). Sixteen out of 21 differentially expressed peaks, including amino acids such as alanine, glycine, proline, and glutamine, and organic acids such as citrate and hexanoate, were identified from spectral dataset, verified by reference standards (Fig.…”

The Complex Functions of Mast Cells in Chronic Human Liver Diseases

“…A further two 3-µm-thick biopsy sections were used for immunohistochemistry in order to recognize the whole inflammatory cell system by treating one with antibodies raised against leukocyte common antigen (DAKO, Milan, Italy) and to distinguish MCs by treating the other with antibodies raised against tryptase (DAKO). The percentages of the biopsy sections covered by collagenous ECM and the inflammatory cell system and the density of the MCs (expressed as the number of cells per square millimeter of available tissue section) were automatically and objectively calculated using a computer-aided image analysis system as previously described [60][61][62]. It was found that 11% of the biopsy tissue section was covered by collagenous ECM, and 5% by the whole inflammatory cell system.…”