In vivo effects of o-coumaric acid on rat liver flavin-containing monooxygenase (fmo) activity and expression

Abstract

Phenolic compounds are biologically active molecules and suggested to have some disease-preventive properties such as cardiovascular and certain types of cancer. Coumaric acid has been known as a phenolic compound and found in a wide variety of plants such as peanuts, tomatoes, carrots, and garlic and form the part of human diet; function as antioxidant and chemopreventive agents. 1-2 Flavin-containing monooxygenases (FMOs, EC 1.14.13.8) are phase I enzymes, responsible for oxygenation of a wide range of nucleophilic heteroatom-containing xenobiotics such as drugs, pesticides, neurotoxins, and other chemicals. They contain FAD in their structure and use NADPH as cofactor and molecular oxygen for their reactions. FMOs can be affected by hormonal and dietary components.3 The aim of this study was to determine the in vivo effects of o-coumaric acid on rat liver FMO activity, protein and mRNA expressions. 30 mg/kg of body weight of o-coumaric acid was intraperitonally injected to 14 albino Wistar rats, while 8 rats were used as control. After 9 days of injection, the rats were decapitated and microsomal fractions of livers were prepared using homogenization and differential centrifugation. FMO enzyme activity of microsomal samples was assayed by using methimazole as substrate. Protein and mRNA expressions were carried out by Western Blot and quantitative Real-Time PCR techniques respectively. The results showed that FMO activity and protein expression were increased 48% and 34%, respectively, by o-coumaric acid injection compared to controls (p<0.05). In addition, o-coumaric acid injection increased the mRNA expression of FMO as 2.1-fold compared to controls (p<0.05). In conclusion, our data suggest that o-coumaric acid found in diet may induce FMO expression and FMO activity enhanced metabolism of drugs, pesticides, and other xenobiotics.