China
Africa
Explore chapters and articles related to this topic
Functions of the Liver
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
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
Published in Hans H. Gadebusch, 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
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
David J. Sweeny, Robert B. Diasio
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).
Purification and characterisation of glutathione reductase from scorpionfish (scorpaena porcus) and investigation of heavy metal ions inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Glutathione reductase (EC 1.8.1.7; GR), a major enzyme in glutathione metabolism, is required for the maintenance of the reduced form of cellular glutathione, which is strongly nucleophilic for many reactive electrophiles10,11. The flavin enzyme GR acts as an antioxidant to protect cells from oxidative stress by reducing glutathione disulphide (GSSG) to its reduced form (GSH)12. It has an important role in the drug and detoxification mechanisms especially in the liver. This is due to the cytochrome P-450 system found in liver microsomes, which provides detoxifying events13. Maintaining the GSH/GSSG ratio in the cell environment is one of the most important known targets of the GR enzyme-catalysed reactions14. Glutathione reductase is involved in the reduction-oxidation of intracellular glutathione for GSSG, which is generated through the detoxification of hydroperoxides and reduction of some other chemicals catalysed by glutathione perdoxidase15. The NADP+ dependent malate dehydrogenase and pentose phosphate pathways provide the NADPH needed in this catalytic process16,17. NADPH, a key product of the pentose phosphate cycle, is employed extensively in reductive biosynthesis. Furthermore, it aids in the protection of the cell against oxidative damage9.
Prevalence of G6PD deficiency in Thai blood donors, the characteristics of G6PD deficient blood, and the efficacy of fluorescent spot test to screen for G6PD deficiency in a hospital blood bank setting
Published in Hematology, 2022
Phinyada Rojphoung, Thongbai Rungroung, Usanee Siriboonrit, Sasijit Vejbaesya, Parichart Permpikul, Janejira Kittivorapart
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked inherited disorder that is characterized by the insufficiency of an enzyme that is used in the pentose phosphate pathway to generate nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is a crucial oxidation reduction molecule that protects red blood cells (RBC) from reactive oxygen species (ROS). Patients with G6PD deficiency manifest varying degrees of acute hemolysis in response to oxidative stress precipitated by certain medications and foods. Transfusion of red cell products from G6PD enzyme deficient donors could cause a potentially unfavorable outcome, especially in newborns and those with hemoglobinopathies [1–3]. Current screening criteria of blood donors relative to red cell disorders in Thailand relies mostly on history taking and point-of-care hemoglobin (Hb) testing. The screening of G6PD deficiency is not performed in the donors at the moment. According to the World Health Organization (WHO) Blood Donor Selection guidelines, only donors with a previous history of hemolysis are to be permanently deferred [4]. However, countries with a high prevalence of G6PD deficiency should establish their own criteria for screening at-risk donors, and they should establish their own transfusion guidelines [5].
Evidence for the efficacy of the emetic PP796 in paraquat SL20 formulations – a narrative review of published and unpublished evidence
Published in Clinical Toxicology, 2022
Paraquat dichloride is a bipyridyl compound that has been widely used as a rapid-acting non-selective contact herbicide since 1962 [1–3]. It exerts its herbicidal activity by interfering with electron transfer, inhibiting the reduction of nicotinamide adenine dinucleotide phosphate (NADP) to nicotinamide adenine dinucleotide phosphate (NADPH) during photosynthesis (PS I electron diversion, HRAC MoA classification 22) [4]. Unfortunately, despite being of moderate acute toxicity to rodents (rat oral LD50 150 mg/kg, WHO hazard class II [5]), it is highly toxic to humans, with deaths after ingestion of small amounts being reported soon after its introduction into agricultural practice [6,7]. Tens of thousands of deaths have occurred from self-poisoning since its introduction [8–11]. Toxicity results from direct corrosive effects on the gut and from oxidative damage, through redox cycling, causing multi-organ failure at high doses of paraquat and lung injury and fibrosis at lower doses [4,12]. Case fatality is often over 50% with liquid 20% paraquat ion (SL20) formulations [10,13]. Treatment is generally ineffective [14].