2.3. Metabolization

Usually, drug metabolism is the process of biochemical transformation using drug metabolism enzymes (DME) of xenobiotics, i.e., exogenous compounds introduced into organisms. The organs and tissues of animals have a diversity of DME that protects the body against both potential harmful substances from the environment (xenobiotics) and certain substances produced by the organism itself (endobiotics) [41]. Detoxification reactions comprise three phases and enzymes: phases I and II consist of metabolization reactions and enzymes, and phase III consists of transporters involved in efflux mechanisms [42]. Enzymes of phase I participate in reactions of conversion, mainly involving oxidation, reduction, and hydrolysis. These are classified as oxidoreductases (such as CYP450 monooxygenases, flavine monooxygenases, cyclooxygenases, and alcohol dehydrogenase) and hydrolases [33, 43]. Conversely, enzymes of phase II participate in reactions of conjugation and inactivation of chemical carcinogens and include transferases. Altogether, enzymes of both phases occurring independently, sequentially, or simultaneously transform xenobiotics into polar water-soluble and excretable metabolites [41]. In mammals, the metabolism of exogenous chemicals is carried out mainly in the liver, the primary site in which CYP450 enzymes are present [44]. Although procarcinogens tend to be chemically stable, they are metabolized in the liver by CYP450, a phase I enzyme, which detoxifies typically xenobiotic compounds. The activity of detoxifying enzymes in phase I is critical for carcinogenic activation of xenobiotics, while the activity of enzymes of phase II is essential for xenobiotic neutralization [45].
