Metabolism of Glutamine and Glutamate in the Liver — Regulation and Physiological Significance
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
The concept of hepatocyte heterogeneity in the liver has been firmly established. This subject has been reviewed by Jungermann and co-workers.79,81 Cells in the periportal zone receive blood directly from the portal circulation and this is rich in oxygen and substrates. Cells in the perivenous region receive blood which is relatively depleted in substrates and oxygen, but enriched in the metabolic products of cells in the periportal region. The cells in these two regions differ somewhat in their enzymic composition and presumably also in their metabolic capacity. This phenomenon has been studied mainly by determination of enzyme activities following microdissection of lyophilized liver sections, and also in some cases by immunohistochemical detection of various enzymes in preparations of intact tissue. As judged by these techniques, the periportal cells contain relatively higher activities of enzymes specifically involved in gluconeogenesis while the perivenous cells have relatively higher contents of enzymes involved in glucose utilization.
Structural Organization of the Liver
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
The hepatocytes are the main functional unit of the liver. Human hepatocytes measure between 15 and 30 μm in greatest dimension with the average diameter of 25 μm. A single mononuclear hepatocyte has an average volume of 11 × 103 μm, which is twice as large as that of rodents, dogs, and cows (4.77 × 103-5.54 × 103 μm3) (Rohr et al., 1976; Weibel et al., 1969). According to Rohr et al. (1976), subcellular organelles subdivide the total volume of the human hepatocyte as follows: nucleus, 6.0%; rough endoplasmic reticulum (RER) 9.4%; smooth endoplasmic reticulum (SER) 5.9%; mitochondria 22%; “dense bodies” (lysosomes) 0.8%; peroxisomes (microbodies) 1.2%; cytosol (ground substance) 45% (Table 1-6). The volumetric composition of organelles in the rat hepatocyte (Table 1-6) (Weibel, 1969) is similar to that of the human hepatocyte. Morphometric data on the hepatic ultrastructure of the rats of different strains and age are available in the following references: Blouin (1983), Blouin et al. (1977), Jones and Schmucker (1977), Loud (1968), Meihuizen and Blahsjaar 1980), Schmucker et al. (1978), and Schmucker and Jones (1975).
Liver, Gallbladder, and Exocrine Pancreas
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
The normally low frequency of proliferating hepatocytes in the adult liver enables regeneration to be readily monitored by a variety of approaches. One approach to monitoring hepatocellular proliferation is by conventional histology. By light microscopy, hepatocellular regeneration may be detected as increased mitotic figures or by nuclear changes such as nucleolar enlargement and usually increase in cytoplasmic basophilia. Hepatocellular regeneration may also be detected histologically as an increased frequency of certain markers using techniques that directly or indirectly label proliferating cells. Among direct methods, immunohistochemical detection of proliferation markers such as Ki67, phospho-histone H3, or proliferating cell nuclear antigen (PCNA) has been utilized (Nolte et al. 2005). Hepatocellular proliferation may also be monitored indirectly by analysis of replicative DNA synthesis in nuclei following premortem labeling with tritiated thymidine (detected autoradiographically) or the thymidine analog, bromodeoxyuridine (detected immunohistochemically; Eldridge et al. 1990). An advantage of the indirect labeling method is that the duration of labeling can be extended to integrate the frequency of S-phase over time. This increases the sensitivity and reduces the variability in response that may occur among groups of animals. Furthermore, the use of both direct and indirect labeling methods for proliferating cells is amenable to automated image analysis to increase the number of cells evaluated.
Advances in the clinical use of collagen as biomarker of liver fibrosis
Published in Expert Review of Molecular Diagnostics, 2020
Steffen K. Meurer, Morten A. Karsdal, Ralf Weiskirchen
Hepatocytes (PC) constitute the main cell mass of the liver. Some early studies implied that isolated hepatocytes are capable of synthesizing collagen I and collagen IV [45-48–49]. It is assumed that pure and homogenous hepatocytes cultured on a basal matrix substrate (laminin- or collagen IV-coated) or interstitial ECM substrate (Collagen I, Fibronectin) are vital, possess a regular metabolism and produce Fibronectin and Collagen IV [50]. Hepatocytes in the healthy liver express collagen XVIII, an expression which is kept high also in fibrosis and cirrhosis [21]. Nevertheless, several other studies indicated that hepatocytes are not the main producers (if at all) of collagens [51-53–54]. Therefore, the contribution of hepatocytes to hepatic collagen production is still discussed controversially. In contrast to HSC, TGF-β1 causes growth arrest in hepatocytes [55]. In order to promote tumorigenesis or to overcome the anti-proliferative effect during regeneration, hepatocytes escape from this control by downregulation of TGF-β receptors rendering those cells insensitive toward this key profibrogenic growth factor [56,57].
Histological and immunohistochemical study of the effect of liraglutide in experimental model of non-alcoholic fatty liver disease
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Mai Salah Nour, Zeinab Abd El-Hay Sakara, Nawal Awad Hasanin, Shereen Mohamed Hamed
H&E-stained liver sections of the control group revealed the normal structure of the classical hepatic lobule which was formed of hepatocytes arranged in plates extending from the central vein (in the center of the lobule) toward the periphery where the portal tract was present. The hepatic plates were separated by blood sinusoids that were lined by endothelial cells and von Kupffer cells. The hepatocytes were polyhedral in shape with central, round and vesicular nucleus. Some hepatocytes were binucleated. The cytoplasm was acidophilic and vacuolated (Figures 1(a) and 2(a)). The FLD group showed hepatocytes that had large, empty vacuole that pushed the nucleus peripherally (signet ring). Hepatocytes had large, multiple empty vacuoles (macrovesicular steatosis). Some hepatocytes with central nucleus showed small empty vacuoles (microvesicular steatosis). Some hepatocytes with darkly stained nuclei and lysed nuclei were detected. Blood sinusoids could not be seen clearly (Figures 1(b) and 2(b)). Mononuclear cellular infiltration and satellitosis (polymorphs encircle ballooned hepatocytes) were also seen (Figure 2(c)). The FLD + Lira group revealed a much better histological picture and most of the hepatocytes had small empty vacuoles. Minimal mononuclear cellular infiltration could be seen (Figures 1(c) and 2(d)).
Assessment of dose-dependent reproductive toxicity of diclofenac sodium in male rats
Published in Drug and Chemical Toxicology, 2019
Archana Vyas, Ashok Purohit, Heera Ram
Beside this, administration of diclofenac also altered non-significantly to the serum cholesterol concentration and glucose. This may be the reason of androgen insufficiency in the treated group because cholesterol is the precursor of the androgens which are important steroid hormones (English et al.2000). Whereas, the reduction in glucose levels may be followed by several mechanisms including decreased synthesis or release of glucose by the liver or increased secretion of insulin or increased peripheral glucose utilization (Fausto et al.2001). The non-significant and significant alterations in serum protein contents were also indicating toxicity of diclofenac treatments which is followed by interference in protein metabolism (Subramanian 2009). The fluctuations in the activity of SGPT transaminases suggest the changes in the concentration of glutamate and aspartate in the extra-cellular environment. Such alterations of their concentrations by the adjuvant may be expected since both glutamate and aspartate are employed in numerous metabolic pathways (Hollands and Logan 1966, Saran et al.2016). Whereas, the hepatocytes have been increasingly applied to identify pharmacological and toxicological responses of drugs. It is illustrated that lactic dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) increased levels taken as serum markers of liver injury seem to damage liver cell induced by oxygen free radicals and the efficacy of the drug (Kučera et al. 2016).
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