Formation of glucoside conjugate of acetaminophen by fungi separated from soil

Huang, Haihua; Lin, Li; Zhang, P.; Qi, Xiu-Lan; Zhong, Dafang

doi:10.1007/bf03191126

Cited by 8 publications

(14 citation statements)

References 16 publications

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“…Based on the molecular structure of the acetaminophen and the characteristic loss of the dehydrosugar, we propose the formation of an O-glucoside, binding the glucose to the hydroxyl group of the benzene ring. The conjugation of paracetamol with 1 U of glucose was already shown for filamentous fungi, separated from soil but not in plants (Huang et al 2006). The conjugation of free paracetamol to either the glutathione or the glucose conjugate is a rapid process: all conjugation products are present right after 3 h of incubation.…”

Section: Discussionmentioning

confidence: 88%

Metabolism of acetaminophen (paracetamol) in plants—two independent pathways result in the formation of a glutathione and a glucose conjugate

Huber¹,

Bartha²,

Harpaintner³

et al. 2009

Environ Sci Pollut Res

124

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Background, aim, and scope Pharmaceuticals and their metabolites are detected in the aquatic environment and our drinking water supplies. The need for high quality drinking water is one of the most challenging problems of our times, but still only little knowledge exists on the impact of these compounds on ecosystems, animals, and man. Biological waste water treatment in constructed wetlands is an effective and low-cost alternative, especially for the treatment of non-industrial, municipal waste water. In this situation, plants get in contact with pharmaceutical compounds and have to tackle their detoxification. The mechanisms for the detoxification of xenobiotics in plants are closely related to the mammalian system. An activation reaction (phase I) is followed by a conjugation (phase II) with hydrophilic molecules like glutathione or glucose. Phase III reactions can be summarized as storage, degradation, and transport of the xenobiotic conjugate. Until now, there is no information available on the fate of pharmaceuticals in plants. In this study, we want to investigate the fate and metabolism of N-acetyl-4-aminophenol (paracetamol) in plant tissues using the cell culture of Armoracia rusticana L. as a model system. Materials and methods A hairy root culture of A. rusticana was treated with acetaminophen in a liquid culture. The formation and identification of metabolites over time were analyzed using HPLC-DAD and LC-MS n techniques. Results With LC-MS technique, we were able to detect paracetamol and identify three of its metabolites in root cells of A. rusticana. Six hours after incubation with 1 mM of acetaminophen, the distribution of acetaminophen and related metabolites in the cells resulted in 18% paracetamol, 64% paracetamol-glucoside, 17% paracetamol glutathione, and 1% of the corresponding cysteine conjugate. Discussion The formation of two independently formed metabolites in plant root cells again revealed strong similarities between plant and mammalian detoxification systems. The detoxification mechanism of glucuronization in mammals is mirrored by glucosidation of xenobiotics in plants. Furthermore, in both systems, a glutathione conjugate is formed. Due to the existence of P450 enzymes in plants, the formation of the highly reactive NAPQI intermediate is possible. Conclusions In this study, we introduce the hairy root cell culture of A. rusticana L. as a suitable model system to study the fate of acetaminophen in plant tissues. Our first results point to the direction of plants being able to take up and detoxify the model substrate paracetamol. These first findings underline the great potential of using plants for waste water treatments in constructed wetlands. Recommendations and perspectives This very first study on the detoxification of a widely used antipyretic agent in plant tissues again shows the flexibility of plant detoxification systems and their potential in waste water treatment facilities. This study covers only the very first steps of acetaminophen detoxification in plants; s...

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Section: Discussionmentioning

confidence: 88%

Metabolism of acetaminophen (paracetamol) in plants—two independent pathways result in the formation of a glutathione and a glucose conjugate

Huber¹,

Bartha²,

Harpaintner³

et al. 2009

Environ Sci Pollut Res

124

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“…Error bars represent standard errors of experimental triplicates nisation is not common in plants, conjugation with glucose can be alternatively found. The formation of glucosides is also described during detoxification of xenobiotics in mammalians (Kirkman et al 1998) and filamentous fungi, separated from soil (Huang et al 2006), but these two independent processes of acetaminophen detoxification in a whole plant system were not described yet.…”

Section: Discussionmentioning

confidence: 96%

Effects of acetaminophen in Brassica juncea L. Czern.: investigation of uptake, translocation, detoxification, and the induced defense pathways

Bartha¹,

Huber²,

Harpaintner³

et al. 2010

Environ Sci Pollut Res

103

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The major metabolic pathways in mammals are conjugation with activated sulfate and glucuronic acid, while a small amount of acetaminophen forms a chemically reactive and highly toxic, hydroxylated metabolite. We identified a glutathionyl and a glycoside conjugate, which refer to the similarities to mammalian detoxification. Increased GST activities in leaf tissues were observed correlated with the appearance of the acetaminophen-glutathione conjugate which shows the involvement of this enzyme group in the metabolism of acetaminophen in plants to organic pollutants and xenobiotics. High acetaminophen concentrations lead to oxidative stress and irreversible damages in the plants, which necessitates further investigations using lower drug concentrations for the deeper understanding of the induced detoxification-and defense processes.

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“…fg-2 Paracetamol 13.23 mM Zhang et al ( 2013 ) Penicillium sp. Paracetamol 0.66 mM Hart and Orr ( 1975 ) Filamentous fungi Paracetamol 0.99 mM Huang et al ( 2006 ) Nocardia sp. NRRL 5646 Ibuprofen 4.85 mM Chen and Rosazza ( 1994 ) Sphingomonas Ibu-2 Ibuprofen 2.42 mM Murdoch and Hay ( 2005 ) Patulinobacter sp.…”

Section: Acetylsalicylic Acid Biodegradation By Microorganismsmentioning

confidence: 99%

“…Furthermore, Huang et al ( 2006 ) described the formation of glucoside conjugates with paracetamol by soil filamentous fungi via O- and N-linkages. This is a similar way to the human detoxication routes of xenobiotics in phase II of detoxication (Halling-Sorensen et al 1998 ).…”

Section: Microbial Degradation and Transformation Of Paracetamolmentioning

confidence: 99%

Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

Marchlewicz

Wojcieszyńska

2015

Water Air Soil Pollut

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Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic non-steroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may be caused by fungal or bacterial microorganisms. Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases. The key intermediate of the paracetamol degradation pathways is hydroquinone. Sometimes, after hydrolysis of this drug, 4-aminophenol is formed, which is a dead-end metabolite. Ibuprofen is metabolized by hydroxylation or activation with CoA, resulting in the formation of isobutylocatechol. The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of over-the-counter anti-inflammatory drugs, their sources and the biotransformation and/or biodegradation pathways of these drugs.

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Formation of glucoside conjugate of acetaminophen by fungi separated from soil

Cited by 8 publications

References 16 publications

Metabolism of acetaminophen (paracetamol) in plants—two independent pathways result in the formation of a glutathione and a glucose conjugate

Metabolism of acetaminophen (paracetamol) in plants—two independent pathways result in the formation of a glutathione and a glucose conjugate

Effects of acetaminophen in Brassica juncea L. Czern.: investigation of uptake, translocation, detoxification, and the induced defense pathways

Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

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