Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen

Abstract

Background: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. Methods: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. Results: The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Conclusion: Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity.

Metabolomic Studies for Metabolic Alterations Induced by Non-Steroidal Anti-Inflammatory Drugs: Mini Review

“…Nine studies (2011-2021) have been performed in the front of metabolomics and NSAIDs. Three of the studies used targeted lipidomics approach [10,37,38] while rest six studies used the approach of untargeted metabolomics [39][40][41][42][43][44]. All studies involved murine subjects.…”

“…Indomethacin stomach 45 mg/kg 6 h Rats Choline(dn), Cis-aconitate(dn), Tryptophan(dn), Spermidine(dn), Trimethylamine(up), N,N-Dimethylglycine(dn), Acetylcarnitine(dn) Creatinine(dn), Pantothenate(dn), Betaine(dn), Carnitine(dn), Isoleucine(dn), Glucose(dn), Kynurenine(dn), Methionine(dn), Acetylcholine(up) NMR [43] In 2017, GC-MS-based metabolomics was used to investigate metabolic effects in rats that were fed aspirin (15 mg/kg) or ibuprofen (15 mg/kg) intragastrically for three weeks [44]. A total of 145 features were identified by the investigators in the three groups of rats.…”

“…The FDR for TCA cycle is 0.0056 for both the drugs. In 2017, GC-MS based metabolomics was used to investigate metabolic effects in rats that were fed aspirin (15 mg/kg) or ibuprofen (15 mg/kg) intragastrically for three weeks [44]. The significant pathways are "synthesis and degradation of ketone bodies" with FDR 0.08 in ibuprofen and FDR of 0.03 in aspirin group respectively.…”