Inhibition of hepatic glutathione transferases by propylthiouracil and its metabolites

Kariya, Kimio; Sawahata, Tadashi; Okuno, Shiroh; Lee, E

doi:10.1016/0006-2952(86)90112-7

Cited by 11 publications

(2 citation statements)

References 22 publications

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“…Lymphocyte activation by PTU has been reported to produce favourable results in a number of cases [24]. There is evidence that PTU and/or its metabolites inhibit glutathione transferase (GST) or glutathione peroxidase (GPx) enzymes in a dose-dependent manner [25]. So, the GSH reserves ran out, which came to an increase in free radicals' concentration compared to SOD, CAT, and GSH concentrations, which in turn damaged liver cells and released the GGT enzyme into the extracellular medium [26].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the hepatoprotective role of ethanolic Saussurea lappa root extract in female rats experimentally exposed to propylthiouracil

Rashed¹,

Rahim²,

Saleh³

2023

Tikrit J. Pure Sci.

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Propylthiouracil (PTU) is often used to produce experimental hypothyroidism. In general, PTU generates hepatotoxicity, albeit with dissimilar incidence rates of hepatotoxicity. This study examined the hepatoprotective effects of Saussurea lappa root ethanol extract on experimentally induced hepatotoxicity in female rats. For this study, 25 adult female albino rats were placed into five equal groups: control, PTU, post treated with S. lappa extract, co-administered PTU with S. lappa extract 300mg/kg, and post-treated with levothyroxine. Serum gamma-glutamyl transferase (GGT) activity, total protein, thyroid hormones (T3, T4, and TSH), and oxidative stress parameters (catalase, superoxide dismutase, reduced glutathione, and lipid peroxidation levels) were measured. The liver tissue underwent histological examination. Current findings revealed that S.lappa ethanol root extract significantly improved hepatotoxicity as evidenced by reversal of various biochemical and histopathological changes in female rats. Current study has shown that this promising impact may be due to the antioxidant and free radical scavenging characteristics of S.lappa constituents.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the hepatoprotective role of ethanolic Saussurea lappa root extract in female rats experimentally exposed to propylthiouracil

Rashed¹,

Rahim²,

Saleh³

2023

Tikrit J. Pure Sci.

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“…PTU or its metabolites might also affect some intracellular targets, which consequently mediate hepatoxicity. Moreover, it was reported that glutathione transferase and glutathione peroxidase were inhibited in a concentration-dependent manner by PTU and its sulfated metabolites [13].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Quantification of Propylthiouracil and Its N-β-d Glucuronide by HPLC-MS/MS: Application to a Metabolic Study

Yao

et al. 2021

Pharmaceuticals

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Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.

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Impairment of sulfobromophthalein biliary excretion and inhibition of glutathione S-transferase activity induced by perhexiline maleate in rats

Mariscal

Muñoz

Collado

et al. 1988

Biochemical Pharmacology

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Inhibition of hepatic glutathione transferases by propylthiouracil and its metabolites

Cited by 11 publications

References 22 publications

Evaluation of the hepatoprotective role of ethanolic Saussurea lappa root extract in female rats experimentally exposed to propylthiouracil

Evaluation of the hepatoprotective role of ethanolic Saussurea lappa root extract in female rats experimentally exposed to propylthiouracil

Simultaneous Quantification of Propylthiouracil and Its N-β-d Glucuronide by HPLC-MS/MS: Application to a Metabolic Study

Impairment of sulfobromophthalein biliary excretion and inhibition of glutathione S-transferase activity induced by perhexiline maleate in rats

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