Pathology of the Liver: Functional and Structural Alterations of Hepatocyte Organelles Induced by Cell Injury
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
The localization of the hepatocyte within the liver lobule is an important determinant of susceptibility to injury. Differences in enzyme composition, organelle distribution, and oxygen tensions are the main determinants of susceptibility to injury. For example, the enhanced susceptibility of centrilobular hepatocytes to hypoxic injury such as occurs in shock is well known. Oxygen tensions are important in the regulation of metabolic reactions in hepatocytes (Marzella et al., 1986). By reversing the flow of perfusate to the perfused liver, the oxygen gradient across the liver lobule can be reversed; rates of some metabolic reactions can be altered and the localization of hepatocyte necrosis within the hepatic lobule can be shifted (Marotto et al., 1988). The susceptibility of the liver to cell injury caused by toxins metabolized by reductive or oxidative metabolism can be, for example, altered by increasing the tissue oxygen tensions with hyperbaric hyperoxia (Bernacchi et al., 1984; Marzella et al., 1986).
Yellow Fever
James H. S. Gear in CRC Handbook of Viral and Rickettsial Hemorrhagic Fevers, 2019
The major diagnostic pathologic changes are found in the liver. The histopathologic changes seen are considered to be specific29 with a high degree of accuracy. In a region with much malaria, pathologic changes of malaria can be seen in most of the fatal cases of yellow fever, even in infants of a year of age.30 The liver is usually normal in size and yellowish. There is necrosis and necrobiosis of parenchymal cells located primarily in the midzone of the liver lobule, but sometimes involving the entire lobule. The necrotic cells are hyaline and eosinophilic, with finely granular appearance of cytoplasm and pycnotic nuclei. Such cells are the so-called “Councilman bodies”. There is no inflammatory reaction evident. Should there be inflammation, it can be considered as due to some concomitant condition. Fatal cases of yellow fever have been seen, with diagnosis confirmed by virus isolation from the liver specimen, where minimal parenchymal cell necrosis can be detected. Other conditions have to be considered when making a diagnosis from liver specimens, among them malaria, hepatitis of several types, changes induced by chemicals or drugs toxic to liver cells, and changes seen in Reyes’ disease, to name a few.
Role of Macrophages and Endothelial Cells in Hepatotoxicity
Timothy R. Billiar, Ronald D. Curran in Hepatocyte and Kupffer Cell Interactions, 2017
Approximately 30 to 35% of the cells in the liver are nonparenchymal cells. The majority of these cells, which include Kupffer cells, endothelial cells, fat-storing cells, and pit cells, reside within the hepatic sinusoids. Epithelial cells and fibroblasts are also found in the liver. The epithelial cells form the walls of the bile ducts, whereas fibroblasts are distributed throughout the liver lobule. Nonparenchymal cells have been largely ignored in studies aimed at elucidating cellular mechanisms of hepatotoxicity, both because of their small size relative to hepatocytes and the small volume they occupy in the liver. However, following exposure to hepatotoxic chemicals, nonparenchymal cells can become “activated”. They release large quantities of highly reactive mediators such as superoxide anion, hydrogen peroxide, nitric oxide, eicosinoids, and proteolytic enzymes which can damage hepatic tissue. These “activated” cells may thus contribute to toxicity.
Metformin ameliorates acetaminophen-induced sub-acute toxicity via antioxidant property
Published in Drug and Chemical Toxicology, 2022
Shambhoo Sharan Tripathi, Sandeep Singh, Geetika Garg, Raushan Kumar, Avnish Kumar Verma, Abhishek Kumar Singh, Akalabya Bissoyi, Syed Ibrahim Rizvi
Figure 2(A,B) explains that the control tissue sections of the liver after H&E staining exhibited normal histology. Tissue section of the metformin group also exhibited normal liver histological architecture (Figure 2(C,D)). Hepatocytes were normal, and no central vein (CV) congestion was prominent in both control as well as metformin groups. Moreover, regular shapes of lobuli were observed and vacuolization of hepatocytes was not seen. In APAP treated group, the section of liver exhibited congestion of CV, infiltration of inflammatory cells, necrotic cells, severe stage of parenchymatous degeneration and vacuolized cytoplasm (Figure 2(E,F)). The nuclei were small and intensely stained. The pathohistological changes were present in whole liver lobule. After metformin treatment in the APAP group, there was improvement in parenchymatous degeneration from a mild to a moderate level (Figure 2(G,H)).
Ferritinophagy was involved in long-term SiNPs exposure induced ferroptosis and liver fibrosis
Published in Nanotoxicology, 2023
Qingqing Liang, Yuexiao Ma, Fenghong Wang, Mengqi Sun, Lisen Lin, Tianyu Li, Junchao Duan, Zhiwei Sun
The H&E staining was performed to evaluate the histopathological effects of SiNPs on rat livers. The images (Figure 1(A)) exhibited that the liver lobule structure was intact and liver cells were arranged neatly in the control group. A few inflammatory cells were observed near the central venous in the livers of rats exposed to SiNPs for a long term. The granulomas were still observed in the vicinity of the central venous after exposure ceased and resumed. The Masson staining results (Figure 1(B)) demonstrated that, compared with the corresponding control group, liver fibrosis appeared near the portal area and the fibrosis area was significantly increased after long-term SiNPs exposure or exposure cessation and recovery (p<0.05) (Figure 1(D)). α-SMA was a marker of hepatic stellate cell activation, and the development of fibrosis was closely related to its level. In this study, the expression level of α-SMA in rat livers was observed by the immunofluorescence method. The immunofluorescence images (Figure 1(C,E)) revealed that, compared with the corresponding control group, α-SMA in the rat liver tissues were obviously upregulated after long-term SiNPs exposure or exposure cessation and recovery (p<0.05).
Hepatocyte Differentiation from iPSCs or MSCs in Decellularized Liver Scaffold: Cell–ECM Adhesion, Spatial Distribution, and Hepatocyte Maturation Profile
Published in Organogenesis, 2022
Radiana Dhewayani Antarianto, Adrian Pragiwaksana, Wahyunia Likhayati Septiana, Nuzli Fahdia Mazfufah, Ameer Mahmood
Native liver scaffold from New Zealand White Rabbit liver was made with decellularization methods by using multiple syringe injection. This method based on previous study that conducted.14 Ten lobules of liver were cut to a size of 1.5 cm x 1.5 cm with a thickness of 0.7–1 cm. The liver cubes were immersed in 0.001 M EGTA for 30 min and placed in a petri dish. A 1- ml syringe was fixed with a fixation device, with red wire attached with a toothpick on top of a styrofoam. The injection using fixated syringe was started with aquadest, continued with graded concentrations of 0.1%, 0.25%, 0.5%, 0.75%, and 1% SDS, and distilled water 25 times at the same point. Injections were carried out at the same site until the liver cube became clear. Further injection was repetitively done on 4–7 sites in the cube. The scaffolds were stored in 0.9% NaCl solution and placed in a freezer at −20°C (Supplementary Figure 1).
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