Unidirectional Inversion of Ibuprofen in Caco-2 Cells: Developing a Suitable Model for Presystemic Chiral Inversion Study

Hao, Haiping; Wang, Guangji; Ding, Zhongxiang; Wu, Xiujie; Roberts, Michael S.

doi:10.1248/bpb.28.682

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…The Caco-2 cell line was validated by STR genotyping while the other cells were not validated. Drug concentrations were chosen based on previously published articles reporting changes in processes in different cell lines and, when possible, specifically in Caco-2 cells, as follows: paracetamol [16][17][18][19][20] and ibuprofen [21][22][23][24][25].…”

Section: Cell Culture and Drug Treatmentsmentioning

confidence: 99%

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Leal

Chen

et al. 2021

COVID

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Ibuprofen is a common over-the-counter drug taken for pain relief. However, recent studies have raised concerns about its potential toxic effect with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been proposed that ibuprofen may increase levels of angiotensin-converting enzyme 2 (ACE2), the human receptor for SARS-CoV-2 infection. Therefore, paracetamol is suggested as an alternative to ibuprofen for treating COVID-19 symptoms. Nevertheless, the relationship between intake of paracetamol or ibuprofen and either susceptibility to infection by SARS-CoV-2 or modulation of cellular ACE2 levels remains unclear. In this study, we combined data from human medical records and cells in culture to explore the role of the intake of these drugs in COVID-19. Although ibuprofen did not influence COVID-19 infectivity or ACE2 levels, paracetamol intake was associated with a lower occurrence of COVID-19 in our cohort. We also found that paracetamol led to decreased ACE2 protein levels in cultured cells. Our work identifies a putative protective effect of paracetamol against SARS-CoV-2 infection. Future work should explore the molecular mechanisms underlying the relationship between paracetamol and COVID-19.

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Section: Cell Culture and Drug Treatmentsmentioning

confidence: 99%

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Leal

Chen

et al. 2021

COVID

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“…Chiral NSAIDs are unlike many other chiral pharmaceuticals in that they can undergo chiral inversion whereby one enantiomer can convert into its antipode (Wsol et al 2004). For example, unidirectional inversion of the biologically less active enantiomer R(−)-ibuprofen to the active enantiomer S(+)-ibuprofen has been reported in in vivo mammalian studies (Hao et al 2005). The inversion process proceeds with an enzyme mediated reaction to form an activated Coenzyme A derivative of R(−)-ibuprofen (Fig.…”

Section: Chiral Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Analysis, fate and toxicity of chiral non-steroidal anti-inflammatory drugs in wastewaters and the environment: a review

Petrie

Camacho‐Muñoz

2020

Environ Chem Lett

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Non-steroidal anti-inflammatory drugs (NSAIDs) are found in the aquatic environment globally. Such drugs including naproxen, ibuprofen and ketoprofen are chiral molecules. Enantiomers of those drugs have identical physicochemical properties but can behave and interact differently in chiral environments due to differences in their three-dimensional shape. This results in enantiospecific differences in environmental fate and toxicity, which is often overlooked. Therefore, we review the analytical methods, occurrence and fate, and toxicity of chiral non-steroidal anti-inflammatory drugs at the enantiomeric level. The advancement of enantioselective chromatography methods, particularly the use of polysaccharide-based stationary phases, has enabled trace determination of enantiomers in complex environmental matrices. Macrocosm and microcosm studies of engineered and natural environments revealed that such drugs can undergo both enantioselective degradation and chiral inversion. Enantioselectivity has been reported during wastewater treatment, in surface waters and in agricultural soils. The use of microcosms spiked with individual enantiomers over racemates is essential to evaluate these degradation and inversion fate processes. The chiral inversion process whereby one enantiomer converts into its antipode can be significant if the more toxic enantiomers are formed. Existing enantiospecific effect studies report less than an order of magnitude difference in enantiomer toxicity. However, toxicity data for enantiomers are limited and further research is needed to better appreciate the environmental risk at the enantiomeric level.

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“…For example, incubation at ˚C resulted in EF changes from 0.00 to 0.28±0.02 in the R(-)-ibuprofen spiked microcosm and from 1.00 to 0.48±0.03 in the S(+)ibuprofen spiked microcosm over 56 d (Figure S14). In vivo mammalian studies have reported unidirectional conversion of R(-)-ibuprofen to S(+)-ibuprofen (Hao et al, 2005). Similarly, fungi such as Verticillium lecanii have been found to preferentially convert R(-)-ibuprofen to S(+)-ibuprofen by an enzymatic process related to mammalian studies (Thomason et al, 1998).…”

Section: Transformation Processes Responsible For Enantiospecific Drug Changesmentioning

confidence: 99%

Enantiospecific behaviour of chiral drugs in soil

Bertin

Yates

Petrie

2020

Environmental Pollution

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The importance of stereochemistry on the behaviour and effects of chiral pharmaceutical and illicit drugs in amended agricultural soils has been over looked to date. Therefore, this study was aimed at investigating the enantiospecific behaviour of a chemically diverse range of chiral drugs including naproxen, ibuprofen, salbutamol, bisoprolol, metoprolol, propranolol, acebutolol, atenolol, chlorpheniramine, amphetamine, fluoxetine and citalopram in soil microcosms. Considerable changes of the enantiomeric composition of ibuprofen, naproxen, atenolol, acebutolol and amphetamine were observed within 56 d. This is significant as enantiomer enrichment can favour the pharmacologically active (e.g., S(-)-atenolol) or less/non-active forms of the drug (e.g., R(-)-amphetamine). Single enantiomer microcosms showed enantiospecific degradation was responsible for enantiomer enrichment of atenolol and amphetamine. However, naproxen and ibuprofen enantiomers were subject to chiral inversion whereby one enantiomer converts to its antipode. Interestingly, chiral inversion was bidirectional and this is the first time it is reported in soil. Therefore, introduction of the less active enantiomer to soil through irrigation with reclaimed wastewater or biosolids as fertiliser can result in the formation of its active enantiomer, or vice versa. This phenomenon needs considered in risk assessment frameworks to avoid underestimating the risk posed by chiral drugs in amended soils. CapsuleChanges to the enantiomeric composition of chiral drugs in soil due to enantiospecific degradation (e.g., atenolol and amphetamine) or chiral inversion (e.g., ibuprofen and naproxen) could result in the underestimation of environmental risk.

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Unidirectional Inversion of Ibuprofen in Caco-2 Cells: Developing a Suitable Model for Presystemic Chiral Inversion Study

Cited by 12 publications

References 29 publications

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Analysis, fate and toxicity of chiral non-steroidal anti-inflammatory drugs in wastewaters and the environment: a review

Enantiospecific behaviour of chiral drugs in soil

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