Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease

Lares‐Asseff, Ismael; Flores‐Pérez, Janett; Juárez-Olguı́n, Hugo; Ramírez-Lacayo, Martha; Loredo-Abdalá, Arturo; Carbajal-Rodríguez, Luis

doi:10.1093/ajcn/69.2.318

Cited by 14 publications

(7 citation statements)

References 15 publications

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“…In this study, we set out to determine if mutations in PIK3CA sensitized breast cancer cells to physiologic doses of aspirin, as determined by the range of basal serum aspirin levels previously described [ 28 , 29 ]. We initially observed only a modest effect of aspirin on cells carrying mutant PIK3CA alone.…”

Section: Discussionmentioning

confidence: 99%

Mutations in PIK3CA sensitize breast cancer cells to physiologic levels of aspirin

Turturro

Najor

Ruby

et al. 2016

Breast Cancer Res Treat

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A review of the literature finds that women diagnosed with breast cancer, who were on an aspirin regimen, experienced a decreased risk of distant metastases and death. Several recent studies have reported an improvement in overall survival in colorectal cancer patients who harbored mutations in the oncogene PIK3CA and received a daily aspirin regimen. Breast cancer patients on a daily aspirin regimen experienced decreased risk of distant metastases and death. PIK3CA is the most frequently mutated oncogene in breast cancer, occurring in up to 45 % of all breast cancers. In order to determine if mutations in PIK3CA sensitized breast cancers to aspirin treatment, we employed the use of isogenic cellular clones of the non-tumorigenic, breast epithelial cell line MCF-10A that harbored mutations in either PIK3CA or KRAS or both. We report that mutations in both PIK3CA and KRAS are required for the greatest aspirin sensitivity in breast cancer, and that the GSK3β protein was hyperphosphorylated in aspirin-treated double knockin cells, but not in other clones/treatments. A more modest effect was observed with single mutant PIK3CA, but not KRAS alone. These observations were further confirmed in a panel of breast cancer cell lines. Our findings provide the first evidence that mutations in PIK3CA sensitize breast cancer cells to aspirin.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3729-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Mutations in PIK3CA sensitize breast cancer cells to physiologic levels of aspirin

Turturro

Najor

Ruby

et al. 2016

Breast Cancer Res Treat

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“…The elimination rate constants of gentisic acid, salicyluric acid and salicylic acid in plasma are slower for underweight children than for normal‐weight children. Underweight children excreted less gentisic and salicylic acids but more salicyluric acid than did normal‐weight children 64. The urine of patients suffering from Reye's syndrome contained significantly more salicylic acid and less gentisic acid than that of patients suffering from juvenile rheumatoid arthritis, while the concentrations of conjugated metabolites were not different between the two groups 65.…”

Section: Absorption and Metabolismmentioning

confidence: 92%

Dietary hydroxybenzoic acid derivatives - nature, occurrence and dietary burden

Tomás‐Barberán

Clifford

2000

J. Sci. Food Agric.

239

110

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Quantitative data for hydroxybenzoic acids (naturally occurring and permitted additives) and their conjugates in foods and beverages are summarised. Tea, rosaceous fruits, red wines and potatoes are important sources for which more comprehensive compositional data are required. Their absorption, metabolism, toxicological evaluation and possible biological significance are discussed. There are insufficient data to properly define the dietary burdens, but it would seem that ellagic acid and gallic acid from natural sources may dominate in many cases, although the intake of added benzoic acid may be of a similar magnitude. It is pointed out that an additional, previously overlooked and possibly significant burden, particularly of benzoic acid itself, might arise as a result of the gut flora metabolism of larger‐mass dietary phenols. © 2000 Society of Chemical Industry

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“…Specifically, antipyrine CL was decreased in underweight adults, 25 while the CLs of acetylsalicylic acid and penicillin decreased in underweight children. 26 27 Different types of CYP450 enzymes are responsible for the metabolism of caffeine and acetylsalicylic acid, while penicillin is usually eliminated without undergoing hepatic metabolism. Acetylsalicylic acid is metabolised by CYP3A4, while caffeine is predominantly metabolised by CYP1A2.…”

Section: Discussionmentioning

confidence: 99%

Lack of a significant change in caffeine metabolism in underweight children as determined by the caffeine breath test

et al. 2015

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ObjectiveLimited data from pharmacokinetic studies in underweight and severely malnourished children have indicated an impaired activity of their hepatic enzymes. We used the caffeine breath test to assess the metabolising activity of cytochrome P450 1A2 (CYP1A2) enzyme in underweight children.MethodsUnderweight children from the paediatric outpatient clinic, Lagos State University Teaching Hospital, Ikeja in Nigeria, were studied. After an overnight fast, 15 underweight children took 3 mg/kg labelled caffeine orally. Breath samples were collected in duplicate at −20, −10 and −1 min and at 15 min intervals for 2 h. The mean cumulative per cent dose recovered (CPDR) of labelled caffeine in the expired carbon dioxide was determined over the study period. This was repeated after 2–6 weeks of nutritional rehabilitation.ResultsThe mean areas under the enrichment-time curve before and after nutritional rehabilitation were 0.539±0.320 and 0.620±0.322 atom per cent excess minute, respectively. The difference between the two values was not statistically significant (p=0.528). The mean CPDR in the exhaled carbon dioxide of the underweight children over a period of 2 h was 7.56±4.01% and 7.95±3.68% before and after nutritional rehabilitation, respectively, and there was no significant difference in the mean values (p=0.603).ConclusionsThe metabolism of caffeine was not significantly affected in underweight children compared with after 2–6 weeks of nutritional rehabilitation. This suggests that hepatic CYP1A2-metabolising activity was not significantly impaired in underweight children.

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Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease

Cited by 14 publications

References 15 publications

Mutations in PIK3CA sensitize breast cancer cells to physiologic levels of aspirin

Mutations in PIK3CA sensitize breast cancer cells to physiologic levels of aspirin

Dietary hydroxybenzoic acid derivatives - nature, occurrence and dietary burden

Lack of a significant change in caffeine metabolism in underweight children as determined by the caffeine breath test

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