Biotransformation of NSAIDs by pig liver microsomes in vitro: Kinetics, metabolites identification and toxicity prediction. (November 2017)

• Record Type: Journal Article
• Authors: Ma, Liyun; Mao, Xiaojing; Sun, Xiao; Xu, Li
• Is Part Of: Chemosphere. Volume 186(2017)
• Page Start: 466
• Page End: 474
• Publication Date: 2017-11
• Subjects: Non-steroidal anti-inflammatory drugs -- Pig liver microsomes -- Biotransformation kinetics -- Metabolites -- Toxicity; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2017.08.026
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used pharmaceuticals in animals. In the current study, the biotransformation of five NSAIDs by pig liver microsomes (PLMs) was studied. The pseudo-first-order kinetics mode was obtained for the metabolization of the studied NSAIDs by PLMs in vitro . The metabolites were identified by high performance liquid chromatography with a high-resolution LTQ-Orbitrap mass spectrometry. The hydroxylation of benzene was confirmed to be the dominating metabolic pathway. Finally, the toxicity of the metabolites was predicted by the Estimation Programs Interface Suite software based on quantitative structure-activity relationships. Decreased toxicity was expected for the most metabolites of the studied NSAIDs except flurbiprofen, whose main metabolite exhibited slightly more toxicity. The present study provided a preliminary foundation to understand the metabolites of some NSAIDs and their toxicity, which was of great significance in animal food safety. Highlights: Five N -arylanthranilic acid derivates were metabolized by pig liver liposome. The hydroxylation of benzene was the dominating metabolic pathway. The toxicity of most metabolites was less than the parent compounds. It was of great significance in animal food safety.