Functions of the Liver
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The breakdown of glucose to carbon dioxide and water with the production of energy is called glycolysis. Glucose catabolism proceeds by two pathways, either by cleavage to trioses producing pyruvic acid and lactic acid (the Embden–Meyerhof pathway) or via oxidation and decarboxylation to pentose (hexose monophosphate shunt). The net energy gain from glycolysis is three molecules of ATP. Pyruvic acid enters the citric acid cycle by conversion to acetic acid with the loss of one molecule of CO2. The citric acid cycle generates 12 molecules of ATP for every molecule of acetic acid. In total, 38 molecules of ATP are produced by the aerobic breakdown of glucose to pyruvate and its incorporation into the citric acid cycle. Pyruvic acid can be formed from the metabolism of amino acids and fat. Glycolysis produces acetyl CoA, which is used as a substrate for lipogenesis and subsequently the production of triglycerides. Another important property of the liver is the formation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. Two NADPH molecules and ribose-5-phosphate are produced from one glucose molecule. NADPH is required for microsomal and mitochondrial hydroxylation of steroid hormones and biotransformation of many drugs.
Phagocytosis By Human Neutrophils
Hans H. Gadebusch in Phagocytes and Cellular Immunity, 2020
The O2- can spontaneously give rise to singlet oxygen that in turn can react with various constituents to generate chemiluminescence. In the presence of NBT dye, the O2- can serve to reduce the dye to the blue formazan. This scheme seems to best fit all the experimental data. In addition, it is consistent with the clinical cases previously described. The defect in chronic granulomatous disease probably lies in an inability of the cell to achieve activation of the oxidase by phagocytosis. In contrast, the syndrome represented by the complete deficiency of glucose-6-phosphate dehydrogenase would be characterized by a normal oxidase enzyme, but the substrate (NADPH) would be unavailable due to congenital absence of the HMS that is required to maintain adequate levels of NADPH.
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 formation of the reactive oxygen species by menadione-stimulated redox cycling can potentially lead to the development of hepatotoxicity. However, under normal conditions the hepatocyte is capable of detoxifying these reactive oxygen species. The superoxide radical can be rapidly dismutated to H2O2, which can be subsequently metabolized by mitochondrial or cytoplasmic glutathione peroxidase. The reduction of H2O2 by glutathione peroxidase occurs at the expense of GSH, leading to the formation of GSSG. The loss of GSH is minimized by the reduction of GSSG by glutathione reductase, utilizing reducing equivalents supplied by NADPH. The capacity of the hepatocyte to reduce GSSG by glutathione reductase appears to be an important means of maintaining a supply of GSH under conditions of oxidative stress, since the toxicity of menadione to isolated hepatocytes is increased in the presence of BCNU, an inhibitor of glutathione reductase (Ross et al., 1986). Moreover, the capacity to supply NADPH for the glutathione reductase system appears to be an important factor in the prevention of oxidative injury. This is suggested by the observation that hepatocytes isolated from rats in which the activity of the pentose pathway (i.e., supply of NADPH) was decreased (e.g., by fasting) were more susceptible to menadione-induced toxicity (Smith et al., 1987).
The nuclear receptor REV-ERBα regulates CYP2E1 expression and acetaminophen hepatotoxicity
Published in Xenobiotica, 2022
Li Zhang, Fugui Zhang, Yifei Xiao, Jianhao Du, Xingwang Zhang, Min Chen, Baojian Wu
APAP and alamethicin were purchased from Aladdin Chemicals (Shanghai, China). Nicotinamide adenine dinucleotide phosphate (NADPH) was obtained from Sigma-Aldrich (St. Louis, MO). p-Nitrophenol was purchased from Macklin Biochemical (Shanghai, China). The assay kits for ALT (alanine aminotransferase) and AST (aspartate aminotransferase) were obtained from Jiancheng Bioengineering Institute (Nanjing, China). Anti-CYP2E1 (ab28146), anti-CYP3A11 (ab3572), and anti-CYP1A2 (ab22717) antibodies were purchased from Abcam (Cambridge, MA). Anti-REV-ERBα (14506-1-AP) and anti-GAPDH (10494-1-AP) antibodies were obtained from Proteintech (Chicago, IL). All primary antibodies were diluted with 5% bovine serum albumin at a ratio of 1:1000. siRev-erbα (siRNA targeting Rev-erbα) and siNC (a negative control for siRev-erbα) were obtained from Tsingke Biotechnology (Beijing China). Short hairpin RNA (shRNA) targeting human REV-ERBα (named shREV-ERBα) and a control shRNA were purchased from Biowit Technologies (Shenzhen, China).
Effects of cinnamaldehyde on glucose-6-phosphate dehydrogenase activity, some biochemical and hematological parameters in diabetic rats
Published in Biomarkers, 2022
Remzi Çelik, Handan Mert, Bahat Comba, Nihat Mert
G6PD, is the first and rate-limiting enzymes of the pentose phosphate gateway produced ribose 5 P and NADPH (Xu et al.2005). As it plays an important role in cell metabolism, it has been found to play a role in the pathophysiology of various diseases such as diabetes, aldosterone stimulating endothelial dysfunction and cancer (Mahmoud and Nor El-Din 2013). The central role of G6PD is that it is a major source of NADPH as a carrier of hydrogen by various essential cellular systems such as glutathione cycle, nitric oxide synthesis, cytochrome P450 system (Stanton 2012). G6PD activity is of great importance in NADPH production, which is required for defense against oxidative stress rather than ribose production (Winzer et al.2001). A complete antioxidant system is based on the producion of NADPH. NADPH is mainly intracellular reductant for all cells. Because G6PD is the source of NADPH, the decrease in activity leads to a decrease in NADPH, which in turn sensitises cells to oxidative damage. Since the change in G6PD activity changes the NADPH level, the antioxidant system is affected (Xu et al.2005).
Novel polymethyl methacrylate modified with metal methacrylate monomers: biological, physicomechanical, and optical properties
Published in Biofouling, 2022
Georgia Arla Cabrera Khader, Andressa da Silva Barboza, Juliana Silva Ribeiro, Monika Lamas Ferreira, Carlos Enrique Cuevás-Suarez, Evandro Piva, Rafael Guerra Lund
This work also evaluated the effect of the incorporation of metal-containing methacrylate compounds on the cell viability of human keratinocytes through the CellTiter 96® Aqueous One Solution test. The CellTiter 96® Aqueous One Solution Reagent contains a tetrazolium compound which is bioreduced by cells into a colored formazan product. This conversion is accomplished by NADPH or NADH produced by dehydrogenase enzymes in metabolically active cells. It is important to emphasize that the incorporation of 10% by weight of metallic monomers in acrylic resins for denture bases promoted cell viability to human keratinocyte cells (HaCaT) similar to previous studies (Cocco et al. 2018; Guimarães et al. 2020). It should also be noted that human keratinocytes are ideal cells for this assay as they are present on the outermost surface of the oral mucosa. The results found are in accordance with ISO 10993-5: 2009, which determines that values with cell viability above 70% are considered biocompatible. It is important to assess the cytotoxicity of potentially antimicrobial biomaterials to rule out possible microbial residual effects due to material toxicity.