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Biotransformation of Xenobiotics in Living Systems—Metabolism of Drugs: Partnership of Liver and Gut Microflora
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Glucuronidation is the most common and the most important conjugation reaction. The UGTs catalyze the transfer of glucuronic acid from donor molecule, uridine-α-glucuronide to a variety of substrates, both endogenous compounds and xenobiotics (Foti and Dalvie, 2016). UGTs are located predominantly in the endoplasmic reticulum of liver, but may be also found in other organs such as kidney, intestine, lungs, prostate, mammary glands, skin, brain, spleen, and nasal mucosa (Penner et al., 2012). Well-characterized endogenous substrates of UGTs include bilirubin, estradiol and serotonin (Foti and Dalvie, 2016). Glucuronidation is an important metabolic pathway for many anesthetic drugs; for example it is the major route of propofol metabolism (Le Guellec et al., 1995). Although the majority of glucuronic conjugates are inactive metabolites, the important exception is morphine-6-glucuronide, as previously mentioned, and the reaction of activation is shown in Fig. 6.12. Regarding the glucuronidation of morphine, two metabolites are formed, morphine-3-glucuronide, which is the major metabolite (45–55%) but inactive and morphine-6-glucuronide (20–30%), which is the more potent analgesic than its parent compound (Christrup, 1997).
HIV-Integrase
Published in Mihai V. Putz, New Frontiers in Nanochemistry, 2020
Corina Duda-Seiman, Daniel Duda-Seiman, Mihai V. Putz
Pharmacokinetics of HIV-integrase inhibitors is a very interesting issue; its understanding of providing information regarding the route of administration, dose, and efficiency. Glucuronidation is the main metabolic pathway of RAL, obtaining RAL glucuronide (RAL-GLU) via UDP-glucuronosyltransferase 1A1 (UGT1A1). RAL and RAL-GLU can be simultaneously detected and quantified using liquid chromatography-tandem mass spectrometry. This method provides knowledge about the therapeutic window of RAL in different patient categories. (Wang et al., 2011). RAL is rapidly absorbed from the gastrointestinal tract when orally administered; peak plasma concentrations are achieved after 0.5–1.3 hours. 9% of the administered dose is excreted unmodified in urine. (Gupta et al., 2015). Recently, a liquid chromatography-tandem mass spectrometry assay was proven to be sufficiently sensitive and accurate to quantify antiretroviral drugs including RAL in plasma and saliva, providing the relationship between drug concentrations in plasma and saliva. (Yamada et al., 2015).
Pharmaceuticals: Some General Aspects
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Other drug-metabolizing biocatalysts are flavin-containing monooxygenases (FMOs). They act mechanistically different from CYP enzymes in that they catalyze the oxidation of organic compounds using NADPH and molecular oxygen. UDP-glucuronosyl transferase (UGT) enzymes, as well as aldehyde oxidase, γ-glutamyl transpeptidase, cathepsin B, and ADP-ribosyltransferase, as examples of non-P450- and non-UGT-mediated metabolism have been reviewed by Fan et al. (2016). The UGT1A and 2B subfamilies are involved in terminating the biological actions and enhancing the renal elimination of lipophilic drugs from all therapeutic classes (Rowland et al., 2013). UDP-glucuronosyl transferase (UGT) enzymes, glutathione transferases (GSTs), sulfotransferases, and N-acetyltransferases are Conjugative DMEs. For example UGT uses UDP-glucuronic acid as a donor to catalyze the glucuronidation of the drug (UDP-glucuronic acid + drug → UDP + drug-glucuronide) resulting in products with enhanced solubility, whereas GSTs catalyze the formation of thioether conjugates between glutathione and reactive xenobiotics.
Antiinflammatory effect of the ethanolic extract of Korean native herb Potentilla rugulosa Nakai in Bisphenol-a-stimulated A549 cells
Published in Journal of Toxicology and Environmental Health, Part A, 2023
Yong Geon Choi, Won Seok Choi, Jin Yong Song, Yubin Lee, Su Hyun Lee, Jong Seok Lee, Sarah Lee, Se Rin Choi, Choong Hwan Lee, Ji-Yun Lee
Figure 1 illustrates phytochemical analysis of PRE tentatively identified 26 metabolites, including 10 flavonoids (procyanidin dimer, catechin, procyanidin trimer, quercetin 3-O-arabino-glucoside, quercetin-O-glucuronide, kaempferol glucuronide, quercetin-acetylhexoside, kaempferol coumaroyl hexose, quercetin, and kaempferol), three cinnamic acids (coumaric acid derivative, caftaric acid, and p-coumaric acid), one carboxylic acid (ethyl citrate), one isocoumarin (brevifolin carboxylic acid), one tannin (ellagic acid pentoside), one triterpene acid (triterpen acid-O-hexoside acetyl), one phenol (dihydrocapsiate), one fatty acyl (roseoside), 6 fatty acid esters (oxo-dihydroxy-octadecenoic acid, 15,16-dihydroxy 9,12-octadecadienoic acid, gingerglycolipid A, 13-HODE, lysoPC [16:0], and lysoPC [18:0]), and one other classification (caffeoyl hexaric acid). These metabolites of PRE were analyzed by ultrahigh-performance liquid chromatography-Q extractive-orbitrap-mass spectrometric (UHPLC-Q-Orbitrap-MS) analysis and annotated based upon their retention times and tandem – mass-spectrometric fragments, as described previously (Table 2).
Cytogenotoxic evaluations of leaves and stems extracts of Rubus rosifolius in primary metabolically noncompetent cells
Published in Journal of Toxicology and Environmental Health, Part A, 2023
Ana Paula Oliveira de Quadros, Isabel Bragança Baraldi, Marcel Petreanu, Rivaldo Niero, Mario Sergio Mantovani, Isabel O’Neill De Mascarenhas Gaivão, Edson Luis Maistro
Although the chemical characterization of R. rosifolius leaf and stem extracts demonstrated the presence of niga-ichigoside, quercetin glucuronide, tormentic acid, and 5,7-dihydroxy-6,8,4ʹ-trimethoxyflavonol as major compounds (Quadros et al. 2020, 2023), different pharmacological effects of each extract indicate the existence of differences in their chemical composition. Petreanu (2017) carried out pharmacological studies with two extracts and observed that the leaf extract exerted an antiproliferative effect on glioma (U251), breast (MCF-7), and kidney (786–0), while stem extract did not produce these effects. On the other hand, the stem extract exhibited gastroprotective effect in the anti-ulcer activity assays, while leaf extract did not produce this effect. In addition to the possibility of chemical differences between extracts of leaves and stems of this plant, the present study, as well as previous investigations conducted by our group with this plant, indicated the presence of genotoxic effects of extracts of aerial parts of R. rosifolius regardless of biotransformation by liver enzymes.
Drying kinetics and effect of air-drying temperature on chemical composition of Phyllanthus amarus and Phyllanthus niruri
Published in Drying Technology, 2018
Adriana Dutra Sousa, Paulo Riceli Vasconcelos Ribeiro, Kirley Marques Canuto, Guilherme Julião Zocolo, Rita de Cassia Alves Pereira, Fabiano André Narciso Fernandes, Edy Sousa de Brito
The results of the PCA of P.amarus and P. niruri extracts obtained by different air-drying temperatures are shown in Figure 4. The PC1 vs. PC2 biplot accounted for 69.79% of the total variance (PC1 = 62.11%, PC2 = 7.68%). In the PCA loadings biplot, the X variables represent all the chemical compounds present in the samples, and the plot demonstrates how the X variables in the data sets correlate with each other. According to Figure 4, P.amarus samples clustered on the left side of the graph and P. niruri samples clustered on the right side. This division indicated that the two species presented significant differences in the composition of their extracts. The difference between the two aforementioned groups occurred along PC1. Sprenger et al.[23] compared the chemical profiles of four Phyllanthus species, including P.amarus and P. niruri, and found vitexin-2″-O-rhamnoside, orientin-2″-O-rhamnoside, and orientin as chemical markers of P. niruri extract; rutin, quercetin-3-O-glucuronide, and kaempferol-3-O-rutinoside were present in P.amarus extract but absent in P. niruri extract.