The Isolated Hepatocyte and Isolated Perfused Liver as Models for Studying Drug- and Chemical-Induced Hepatotoxicity
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
The parenchymal cell (hepatocyte) is the main functional unit of the liver, constituting 60% of the liver cell population and 80% of the total liver volume. Because of the vast number and size of hepatocytes relative to other cell types (i.e., Kupffer and endothelial) in the liver, the isolation of hepatocytes from whole liver has become a fairly simple and routine procedure. Hepatocytes can be isolated from practically any species (e.g., chicken, fish, human), but those from rodent, especially the rat, are the most widely used in drug metabolism and toxicity studies. The present chapter therefore describes the use of isolated rat hepatocytes as a model for studying drug- and chemical-induced hepatotoxicity. While isolated rat hepatocytes in culture have been suggested to be useful for certain toxicological studies (McQueen and Williams, 1987), the present chapter deals exclusively with the use of freshly isolated suspensions of hepatocytes.
The patient with acute gastrointestinal problems
Peate Ian, Dutton Helen in Acute Nursing Care, 2020
The liver is dark reddish-brown in colour and is divided into two main lobes (the larger right and the smaller left) which are further subdivided into approximately 100,000 small lobes, or lobules. About 60% of the liver is made up of liver cells called hepatocytes, which absorb nutrients and detoxify and remove harmful substances from the blood. A hepatocyte has an average lifespan of 150 days. There are approximately 202,000 hepatocytes in every milligram of liver tissue. The liver receives its blood supply via the hepatic artery and portal vein. Instead of capillaries, the liver has large endothelium lined spaces (sinusoids) through which blood passes. The sinusoids also contain fixed phagocytes called stellate reticuloendothelial (Kupffer) cells which perform several functions, including the breakdown of worn out red blood cells, bacteria and other foreign matter which can then pass into the venous circulation.
Liver, Gallbladder, and Exocrine Pancreas
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
The parenchymal cell of the liver, the hepatocyte, is responsible for the key metabolic and exocrine functions of the liver and is most often the target cell of hepatotoxicity. Hepatocytes are structurally arranged in cords that are lined by a specialized sinusoidal endothelium that is fenestrated and lacks basement membrane (Braet and Wisse 2002). This facilitates free exchange of blood solutes with the subendothelial membrane of the hepatocytes. Hepatocytes are connected to each other by gap junctions and tight junctions, the latter forming bile canaliculi, which are lined by the plasma membrane at the excretory pole of adjacent hepatocytes. The canaliculi form the channels for bile flow from the hepatocytes through the canals of Herring into the portal bile ducts that ultimately merge and conduct the bile out of the liver.
Microanatomy of the metabolic associated fatty liver disease (MAFLD) by single-cell transcriptomics
Published in Journal of Drug Targeting, 2023
Lijun Wang, Kebing Zhou, Qing Wu, Lingping Zhu, Yang Hu, Xuefeng Yang, Duo Li
Metabolic-associated fatty liver disease remains a prominent risk factor for many chronic diseases, including obesity, diabetes, cardiovascular disease, and cancer [16]. Moreover, MAFLD can progress to steatohepatitis or cirrhosis. However, there is no definite target and therapeutic mechanism for MAFLD. Single-cell sequencing has guiding significance for screening potential therapeutic targets and molecular mechanisms of MAFLD. In the present study, we conducted transcriptome profiling of 30,038 single cells, including hepatocytes and non-hepatocytes, from normal and steatosis adult mouse livers. Comparative analysis of hepatocytes and non-hepatocytes revealed significant heterogeneity, and non-hepatocytes acted as major cell communication hubs. Systematic analysis of cellular compositions and cell-cell interaction networks showed that hepatocyte metabolism was significantly correlated with changes in liver function. We also uncovered the active involvement of non-hepatocyte cells in regulating the behaviour of hepatocytes, exemplified by Kupffer cells, which could preserve liver function after steatosis.
Mitochondrial dysfunction and mitochondrion-targeted therapeutics in liver diseases
Published in Journal of Drug Targeting, 2021
Li Xiang, Yaru Shao, Yuping Chen
Well-being mitochondria warrant cell, tissue and organ to carry out energy and matter metabolism so its dysfunction associates with aetiologies of human diseases including metabolic syndrome and cancer [3]. Liver function is closely related to the mitochondrial vigour of liver cells, especially of hepatocytes which bear the most of liver responsibility. Mitochondrial metabolic and functional abnormalities and its initiated apoptosis play important roles in the occurrence and development of liver diseases from fatty liver to HCC [4]. Mitochondrial DNA (mtDNA) integrity, membrane composition, redoxidation balance and metabolic supply and demand all affect their function and structure. To maintain their own health, mitochondria incite mitochondrial quality control (MQC) mechanism to prevent further injury to cells, including fission and fusion, mitophagy and biogenesis, etc. [5]. Agents correcting mitochondrial abnormalities, particularly targeting the MQC system, have thus been shown to serve as therapeutic options for liver diseases.
Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis
Published in Pharmaceutical Biology, 2021
Yuan Zhou, Rong Wu, Fei-fei Cai, Wen-Jun Zhou, Yi-Yu Lu, Hui Zhang, Qi-Long Chen, Ming-Yu Sun, Shi-Bing Su
Liver fibrosis is a pathological condition characterized by the replacement of normal liver tissue with scar tissue due to a variety of liver diseases, such as hepatitis B, hepatitis C, autoimmune liver diseases, as well as alcohol-induced or non-alcoholic fatty liver disease. It occurs due to repeated damage and repair processes, which are directly related to excessive accumulation of the extracellular matrix (Seki and Schwabe 2015). Excessive liver fibrosis can lead to hepatic cirrhosis and loss of liver function as well as digestive tract bleeding and hepatocellular carcinoma (Koyama and Brenner 2015). Liver fibrosis is involved in multiple liver cell types, including hepatic parenchymal cells, Kupffer cells, endothelial cells, hepatic stellate cells (HSCs), and infiltrated blood inflammatory cells, which proliferate and replace lost liver cells and produce the extracellular matrix in the injured liver (Higashi et al. 2017). Molecularly, upon the expression of liver disease-induced fibrogenic factors, such as transforming growth factor-β (TGF-β) as a profibrotic mediator, HSCs start to proliferate from their quiescent state due to the loss of cytoplasmic retinoids into proliferative and fibrogenic myofibroblasts, which express α-smooth muscle actin (α-SMA) and extracellular matrix type I, III and IV collagen, and depose them into the space of the lost hepatic parenchymal cells, resulting in liver fibrosis (Tsuchida and Friedman 2017). However, the molecular mechanisms of hepatic fibrogenesis remain to be defined, and there is still a lack of effective drugs for the treatment of liver fibrosis (Yoon et al. 2016).
Related Knowledge Centers
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- Carbohydrate
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- Cholesterol
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