Browsing by Subject "Rat liver"

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    Decreased density of ß1-adrenergic receptors in preneoplastic and neoplastic liver lesions of F344 rats
    (Murcia : F. Hernández, 2005) Cardani, R.; Zavanella, T.
    There is some evidence that rodent hepatocarcinogenesis is accompanied by changes in the adrenergic responsiveness of liver cells to catecholamines. In this study, immunohistochemical expression of ß1-adrenergic receptors (ß1-ARs) has been examined in spontaneous and chemically induced preneoplastic and neoplastic liver lesions of female and male Fischer 344 rats. An antibody specific for ß1-AR subtype was used. The study was carried out on archival formalin-fixed and paraffin-embedded livers from rats used in a previous study of hepatocarcinogenesis. One control group given distilled water by gavage, and two experimental groups, one initiated with a single dose of diethylnitrosamine (DEN) and one initiated with DEN and continuously treated with phenobarbital (PB) were examined. Rats were sacrificed after 2, 4, 8 and 21 months of experimentation. All types of liver putative preneoplastic lesions examined (basophilic, glycogenretaining, or mixed cell foci) show a lower density of ß1- ARs than the surrounding normal liver parenchyma, either in control and in DEN-treated or DEN+PB-treated rats. No immunostaining is detectable in several altered cell foci. Hepatocellular adenomas and hepatocellular carcinomas also show a very low density of ß1-ARs, extensive areas completely devoid of ß1-ARs being mingled with areas showing a weak immunostaining.
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    Subchronic toxicity of 3,3',4,4'-tetrachlorobiphenyl in the rat liver. An electron microscope study
    (Murcia : F. Hernández, 1994) MacLellan, K.; Singhl, A.; Chu, I.; Villeneuve, David C.
    Ultrastructural effects of 3,3'4,4'-tetrachlorobiphenyl (PCB) congener #77 on the liver were evaluated following its feeding to Sprague-Dawley weanling rats. Treatment diets were prepared by dissolving the congener in 4% corn oil. Ten animals, either male or female, in each group were placed on the respective diets containing 10, 100, 1.000 and 10,000 ppb congener for 13 weeks. Ten animals of each sex served as the control that had only the oil added to the diets. In the congener-exposed animals the alterations consisted of a marked increase in the profiles of smooth endoplasmic reticulum, and in the heightened number of lipid droplets in many parenchyma1 cells. Several mitochondria showed abnormalities such as dumbbell shapes, and in others, the cristae were oriented parallel to the long axis of the organelle. Peroxisomes were numerous in the 10 ppb group and apparently had increased numerically in the liver of animals from the higher dose groups. Females were notably more affected by the congener when compared to their male counterparts. The results indicated that the compound is mildly toxic, and alteration in structure and function can be noted at the lowest dose used (10 ppb congener exposure). It is concluded that congener #77 may be moderately toxic and it may affect the overall health of the exposed animal.
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    Upregulation of fibronectin but not of entactin, collagen IV and smooth muscle actin by anaphylatoxin C5a in rat hepatic stellate cells
    (Murcia : F. Hernández, 2004) Schlaf, G.; Schmitz, M.; Heine, I.; Demberg, T.; Götze, O.
    Rat Kupffer cells (KC), hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC) all express the C5a receptor (C5aR) constitutively in contrast to hepatocytes (HC). HSC showed an unexpectedly high level of expression of the C5aR. As these cells are known to play a key role in the induction of liver fibrosis we hypothesized that C5a may possibly induce fibrogenetic proteins in these cells. HSC are known to express the extracellular matrix (ECM) proteins collagen IV, fibronectin, entactin and the structure protein smooth muscle actin (SMA) which is regarded as a marker for the fibrotic conversion of HSC to myofibroblast-like cells. We investigated the effect of recombinant rat C5a (rrC5a) on the upregulation of these ECM-proteins and of SMA, all of which are known to be expressed by HSC. The profibrotic cytokine TGF-ß1 (2 ng/ml), which was used as a control, clearly upregulated the three matrix proteins but not SMA. In the absence of any stimulus HSC upregulated the three ECM-proteins as well as SMA during their conversion into myofibroblastlike cells. This resulted in a high stimulus-independent plateau of the mRNA expressions for all four proteins after four to five days of culture. Readouts were therefore taken at 72 h after the isolation of the HSC when the investigated mRNA levels had not yet reached their maxima due to the conversion of the cells. The first 24 h of culture were performed without stimulus and the following 48 h in the presence of 100 nM rrC5a (1 µg/ml) or TGF-ß1 (2 ng/ml). Only fibronectin-specific mRNA was clearly upregulated by C5a whereas entactin, collagen IV and SMA were not affected by C5a. By competitive-quantitative PCR the upregulation of fibronectin-specific mRNA was determined to be about five-fold. As TGF-ß1 upregulated all of the three investigated ECM-proteins but not SMA it was checked as to whether C5a might act indirectly by upregulating the expression of TGF-ß1 in KC and HSC, as both cell types are known to be sources of this profibrotic cytokine. However, using RT-PCR, such an effect was not detectable in either cell type after 3, 10 or 24 h.