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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).
IDH1 and IDH2 Mutations as Novel Therapeutic Targets in Acute Myeloid Leukemia (AML): Current Perspectives
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Angelo Paci, Mael Heiblig, Christophe Willekens, Sophie Broutin, Mehdi Touat, Virginie Penard-Lacronique, Stéphane de Bottona
Enasidenib is known to inhibit UDP glucuronosyltransferase 1A1 (UGT1A1), and induced elevation of unconjugated bilirubin (up to 83% of the treated patients) (Stein et al., 2017; 2019) as in Gilbert’s disease but with no serious consequences.
Pharmacokinetics of α-amanitin in mice using liquid chromatography-high resolution mass spectrometry and in vitro drug–drug interaction potentials
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Ria Park, Won-Gu Choi, Min Seo Lee, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Chang Hwan Sohn, Im-Sook Song, Hye Suk Lee
α-Amanitin did not markedly inhibit UGT1A1-catalyzed SN-38 glucuronidation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-β-glucuronidation, UGT1A4-catalyzed trifluoperazine N-β-D-glucuronidation, UGT1A6-catalyzed N-acetylserotonin β-D-glucuronidation, UGT1A9-catalyzed mycophenolic acid β-D-glucuronidation, and UGT2B7-catalyzed naloxone 3-β-D-glucuronidation at 50 μM in HLMs (Figure 5).
Nexus between perfluoroalkyl compounds (PFCs) and human thyroid dysfunction: A systematic review evidenced from laboratory investigations and epidemiological studies
Published in Critical Reviews in Environmental Science and Technology, 2021
Weiping Xie, Wei Zhong, Brice M. R. Appenzeller, Jianqing Zhang, Muhammad Junaid, Nan Xu
Exposure to PFCs may not always directly lead to alterations in the transcriptional levels of thyroid-sensitive genes. In other words, the transcriptional levels of the genes may be influenced by the reduction of TH levels or thyroid dysfunction (e.g. T3/T4 alterations, thyroid development, etc.), which may be a result of PFC exposure (Dong et al., 2016; Shi et al., 2008; Yu et al., 2009). Uridine diphospho-glucuronosyltransferases (UGTs) are capable of inducing regulatory effects during TH homeostasis. PFOS exposure enhanced T4 metabolism and excretion in rats by inducing ugt1a1 expression, which raised the glucuronidation and subsequent elimination of T4 in the liver (Yu et al., 2009). PFHxS significantly decreased plasma free thyroxine (FT4) levels in chicken embryonic neuronal cells and upregulated the mRNA expression levels of type II and type III 5′-deiodinases (d2 and d3) (Cassone et al., 2012). PFHxS decreased the expression of gene d3, neurogranin (rc3), and transthyretin (ttr), while perfluorohexanoic acid (PFHxA) treatment upregulated expression levels of d2 and d3 (Vongphachan et al., 2011). Exposure to PFOA at the 500 μg/L level significantly upregulated the expression levels of marker genes (hhex and pax8) related to early thyroid development by 1.6-fold and 2.4-fold in zebrafish, respectively (Du, Huang, et al., 2013). PFOS also induced developmental toxicity in zebrafish and significantly upregulated the expression of hhex and pax8 (Du, Hu, et al., 2013). PFOA was potentially associated with the transcriptional activation of thyroid-hormone-dependent genes such as malic enzyme (me), mitochondrial glycerol-3-phosphate dehydrogenase (g3pd), glucose-6-phosphate dehydrogenase (g6pd) and spot 14 (s14). Chang et al. (2008) observed that the expression of me increased after 2 h of PFOS exposure. PFDA exposure induced hyperactivity of glycerophosphate dehydrogenase in rats (Gutshall et al., 1988). Further, deiodinase activity is critical for the regulation of TH levels and acts as a sensitive biomarker to indicate thyroid disturbance upon exposure to high concentrations of PFCs. Two microsomal iodothyronine deiodinases, type I (Dio1) and type II (Dio2) accomplish the conversion of the majority of T4–T3. Shi et al. (2009) revealed significant upregulation of dio1 and trα, and downregulation of trβ and ttr in zebrafish after 15 days postfertilization (dpf) of PFOS exposure, which as a consequence, significantly increased T3 levels. Similarly, PFDoA treatment significantly increased the expression levels of dio1 and dio2 and decreased TH levels, implying hypothyroidism in zebrafish after PFC exposure (Zhang et al., 2018).