Changes in hepatic metabolic enzyme activities and biliary excretion of 4-nitrophenol in streptozotocin induced diabetic rats

Almási, Attila; Pinto, Évora Da Ibéria Leite Nogueira; Kovács, Noémi Piroska; Fischer, Tamás; Markovics, Zoltán; Fischer, E.; Perjési, Pál

doi:10.1590/s2175-97902018000117347

Cited by 5 publications

(8 citation statements)

References 30 publications

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“…Formation of phenyl glucuronides and phenyl sulfates are generally considered to be detoxification processes [56]. As our present and previous results [22,23,29,30,34] demonstrate, the formed phenol conjugates can be reexcreted into the gastrointestinal system both by the liver and the small intestine. At the lower PNP concentrations (up to 500 µM), a higher fraction of the absorbed dose is reexcreted into the small intestine in the PNP-G form.…”

Section: Discussionsupporting

confidence: 73%

“…Earlier, we investigated the intestinal disappearance as well as the intestinal and hepatic phase II metabolism of p-nitrophenol in control and STZ-treated experimental animals [19][20][21][22][23]. p-Nitrophenol (PNP) was used as a model compound because it is well known that that PNP is metabolized almost exclusively by phase II metabolic reactions, namely by conjugation with glucuronic acid and sulfate [19,[24][25][26][27][28], to form the metabolites p-nitrophenyl glucuronide (PNP-G) and p-nitrophenol sulfate (PNP-S).…”

Section: Of 14mentioning

confidence: 99%

“…Using this experimental protocol, we aimed to collect simultaneous data on the amount of PNP and its two phase II conjugates excreted to the small intestine by the gut epithelium and the liver (through the bile). The parent compound and the metabolites were determined by our previously developed, validated HPLC methods [19,22,23,29,30].…”

Section: Of 14mentioning

confidence: 99%

“…The experiments were performed according to the protocol used before [19][20][21][22][23]29,30]. Male Wistar rats (weighing 220-250 g) were used.…”

Section: Animals and Experimental Proceduresmentioning

confidence: 99%

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The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

2020

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Intestinal and hepatic function have been investigated in phase II metabolic reactions and elimination of p-nitrophenol (PNP) in the rat. A jejunal loop was cannulated and recirculated with isotonic solutions containing PNP in different concentrations (0, 20, 100, 500, 1000 µM). Samples were obtained from the perfusate at given intervals. To investigate the metabolic and excretory functions of the liver, the bile duct was cannulated, and the bile was collected. Metabolites of PNP were determined by validated HPLC (high pressure liquid chromatography) methods. The results demonstrated the relative importance of the small intestine and the liver in phase II metabolic transformations and elimination of PNP. There were significant differences between the luminal and biliary appearances of p-nitrophenol-glucuronide (PNP-G) and p-nitrophenol–sulfate (PNP-S). The PNP-G appeared in the intestinal lumen at the lower PNP concentrations (20 µM and 100 µM) at higher rate than in the bile. No significant difference was found between the intestinal and the biliary excretion of PNP-G when PNP was administered at a concentration of 500 µM. However, a reverse ratio of these parameters was observed at the administration of 1000 µM PNP. The results indicated that both the small intestine and the liver might play an important role in phase II metabolic reactions and elimination of PNP. However, the relative importance of the small intestine and the liver can be dependent on the dose of drugs.

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Section: Discussionsupporting

confidence: 73%

Section: Of 14mentioning

confidence: 99%

Section: Of 14mentioning

confidence: 99%

“…The experiments were performed according to the protocol used before [19][20][21][22][23]29,30]. Male Wistar rats (weighing 220-250 g) were used.…”

Section: Animals and Experimental Proceduresmentioning

confidence: 99%

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The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

2020

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“…Activity of the UDP-glucuronyltransferase was significantly decreased in the liver of the STZ-treated rats. On the other hand, activity of the sulfotransferase and the respective hydrolytic enzymes did not change significantly [14]. According to these observations, we found the biliary excretion of ibuprofen glucuronide (IBP-GLU) in the STZ-treated (hyperglycemic) experimental animals statistically lower than in the controls [15].…”

Section: Introductionmentioning

confidence: 59%

The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia

Mohammed

Almási²,

Molnár³

et al. 2022

Molecules

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Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyzed oxidative metabolites. The present work aimed to investigate how experimental hyperglycemia affects the intestinal and biliary appearance of the oxidative and Phase II metabolites of ibuprofen in rats. In vivo studies were performed by luminal perfusion of 250 μM racemic ibuprofen solution in control and streptozotocin-treated (hyperglycemic) rats. Analysis of the collected intestinal perfusate and bile samples was performed by HPLC-UV and HPLC-MS. No oxidative metabolites could be detected in the perfusate samples. The biliary appearance of ibuprofen, 2-hydroxyibuprofen, ibuprofen glucuronide, hydroxylated ibuprofen glucuronide, and ibuprofen taurate was depressed in the hyperglycemic animals. However, no specific non-enzymatic (hydroxyl radical initiated) hydroxylation product could be detected. Instead, the depression of biliary excretion of ibuprofen and ibuprofen metabolites turned out to be the indicative marker of hyperglycemia. The observed changes impact the pharmacokinetics of drugs administered in hyperglycemic individuals.

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Metal–Organic Framework-Based Composite for Photocatalytic Detection of Prevalent Pollutant

Liu

Dordick²,

Dinu

2019

ACS Appl. Mater. Interfaces

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Photocatalytic properties of 2,5-furandicarboxylic acid (FDCA), a model organic molecule used for biopolymer production, are reported for the first time. Further integration of FDCA into metal–organic framework (MOF) structures and subsequent silver-based photoactivation leads to the next generation of hybrids with controlled morphologies, capable of forming sensorial platforms for prevalent phenol contaminant detection. The mechanisms that allow photocatalytic functionality are driven by the charge carrier generation in the organic molecule (either in its alone or integrated form) and depend on sample’s physical and chemical properties as confirmed by scanning and transmission electron microscopy, Fourier transform infrared and X-ray photoelectron spectroscopy, and X-ray diffraction, respectively. Electrochemical analysis using cyclic voltammetry confirmed high sensitivity for p-nitrophenol (p-NP) detection as dictated by the selective electron migration at a user-controlled electrode interface. Considering the wide usage of p-NP and its increased discharge shown to lead to harmful effects on both the environment and biosystems, this new detection method is envisioned to allow effective control and regulation of such compound release, all under low-cost and environmentally friendly conditions.

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Changes in hepatic metabolic enzyme activities and biliary excretion of 4-nitrophenol in streptozotocin induced diabetic rats

Cited by 5 publications

References 30 publications

The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia

Metal–Organic Framework-Based Composite for Photocatalytic Detection of Prevalent Pollutant

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