Induction of Peroxisomal β-Oxidation by Nonsteroidal Anti-inflammatory Drugs

Foxworthy, Patricia S.; Perry, David N.; Eacho, Patrick I.

doi:10.1006/taap.1993.1033

Cited by 20 publications

(5 citation statements)

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“…Much to our surprise, ibuprofen exerted a beneficial influence on lipid metabolism by increasing HDL levels in smokers and non‐smokers, and reducing triglyceride levels in smokers. The structure of the drug resembles that of clofibric acid [43]. Foxworthy et al .…”

Section: Discussionmentioning

confidence: 99%

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Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non‐smokers

Zapolska-Downar

Naruszewicz

Zapolski-Downar

et al. 2000

Eur J Clin Investigation

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Section: Discussionmentioning

confidence: 99%

“…Foxworthy et al . [43] have found that ibuprofen, just like clofibric acid, increases peroxisomal β‐oxidation in cultured rat hepatocytes. Following a 2‐week dietary administration to rats, ibuprofen reduced serum lipids.…”

Section: Discussionmentioning

confidence: 99%

Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non‐smokers

Zapolska-Downar

Naruszewicz

Zapolski-Downar

et al. 2000

Eur J Clin Investigation

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“…In addition to acyl glucuronidation, carboxylic acid drugs may undergo metabolism to CoA-thioesters, which may further become metabolized to amino acid conjugates or take part in lipid neogenesis (10)(11)(12)(13) or β-oxidation (14)(15)(16). Because of the chemical nature of the thioester bond, the CoA thioesters of carboxylic acids are more reactive than the corresponding 1-O-acyl glucuronides (8,9,17).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Reactivity of Carboxylic Acid-CoA Thioesters with Glutathione

Sidenius

Skonberg

Olsen

et al. 2003

Chem. Res. Toxicol.

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The chemical reactivity of acyl-CoA thioesters toward nucleophiles has been demonstrated in several recent studies. Thus, intracellularly formed acyl-CoAs of xenobiotic carboxylic acids may react covalently with endogenous proteins and potentially lead to adverse effects. The purpose of this study was to investigate whether a correlation could be found between the structure of acyl-CoA thioesters and their reactivities toward the tripeptide, glutathione (gamma-Glu-Cys-Gly). The acyl-CoA thioesters of eight carboxylic acids (ibuprofen, clofibric acid, indomethacin, fenbufen, tolmetin, salicylic acid, 2-phenoxypropionic acid, and (4-chloro-2-methyl-phenoxy)acetic acid (MCPA)) were synthesized, and each acyl-CoA (0.5 mM) was incubated with glutathione (5.0 mM) in 0.1 M potassium phosphate (pH 7.4, 37 degrees C). All of the acyl-CoAs reacted with glutathione to form the respective acyl-S-glutathione products, with MCPA-CoA having the highest rate of conjugate formation (120 +/- 10 microM/min) and ibuprofen-CoA having the lowest (1.0 +/- 0.1 microM/min). The relative reactivities of the acyl-CoAs were dependent on the substitution at the carbon atom alpha to the acyl carbon and on the presence of an oxygen atom in a position beta to the acyl carbon and were as follows: phenoxyacetic acid > o-hydroxybenzoic acid--phenoxypropionic acid > arylacetic acid derivatives > 2-methyl-2-phenoxypropionic acid--2-phenylpropionic acid. For each acyl-CoA thioester, the overall hydrolysis rate was determined as the time-dependent formation of parent compound. A linear trend was observed when comparing the reactivities of the acyl-CoAs with glutathione with the corresponding overall hydrolysis rates. Thus, the most reactive compound (MCPA-CoA) was also the compound with the highest rate of hydrolysis and the least reactive compounds (ibuprofen-CoA, clofibryl-CoA) were also the compounds least susceptible to hydrolysis.

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“…Certain NSAIDs are also ligands for the PPAR-α form [56]. Several NSAIDs have marked effects on peroxisome activity in rodent hepatocytes when used either in vitro or in vivo [58,59], and it appears likely that these effects are mediated by PPAR-α activation.…”

Section: Synthetic and Natural Ligands Of Pparsmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors and Shock State

Esposito

Cuzzocrea²,

Meli³

2006

The Scientific World JOURNAL

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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of PPARs have been identified: alpha, beta/delta, and gamma, encoded by different genes and distributed in various tissues. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and, thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert anti-inflammatory effects by inhibiting the induction of proinflammatory cytokines, adhesion molecules, and extracellular matrix proteins, or by stimulating the production of anti-inflammatory molecules. Moreover, PPARs modulate the proliferation, differentiation, and survival of immune cells. This review presents the current state of knowledge regarding the involvement of PPARs in the control of inflammatory response, and their potential therapeutic applications in several types of shock, as well as hemorrhagic, septic, and nonseptic shock.

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Induction of Peroxisomal β-Oxidation by Nonsteroidal Anti-inflammatory Drugs

Cited by 20 publications

References 0 publications

Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non‐smokers

Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non‐smokers

In Vitro Reactivity of Carboxylic Acid-CoA Thioesters with Glutathione

Peroxisome Proliferator-Activated Receptors and Shock State

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