Abstract
Cytochromes are expressed in many different tissues of the human body. They are found mostly in intestinal and hepatic tissues. Cytochromes P450 (CYPs) are enzymes that oxidize substances using iron and are able to metabolize a large variety of xenobiotic substances. CYP enzymes are linked to a wide array of reactions including and O-dealkylation, S-oxidation, epoxidation, and hydroxylation. The activity of the typical P450 cytochrome is influenced by a variety of factors, such as genus, environment, disease state, herbicide, alcohol, and herbal medications. However, diet seems to play a major role. The mechanisms of action of dietary chemicals, macro- and micronutrients on specific CYP isoenzymes have been extensively studied. Dietary modulation has effects upon the metabolism of xenobiotics. Cytochromes harbor intra- or interindividual and intra- or interethnic genetic polymorphisms. Bacteria were shown to express CYP-like genes. The tremendous metabolic activity of the microbiota is associated to its abundant pool of CYP enzymes, which catalyze phase I and II reactions in drug metabolism. Disease states, intestinal disturbances, aging, environmental toxic effects, chemical exposures or nutrition modulate the microbial metabolism of a drug before absorption. A plethora of effects exhibited by most of CYP enzymes can resemble those of proinflammatory cytokines and IFNs. Moreover, they are involved in the initiation and persistence of pathologic pain by directly activating sensory neurons and inflammatory cytokines.
Highlights
Over centuries the human immune system has evolved to battle against pathogenic microorganisms
As stated previously [2, 3], expression of CYPs enzymes is mainly downregulated in the hepatic tissue during the host response to inflammation or infection, inducing changes in drug activity, and resulting in toxin release. Proinflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor α (TNFα) are the key inflammatory mediators modulating the synthesis of acute phase proteins (APP) in inflammation
It should be mentioned that inflammation is associated with downregulations of hepatic and extrahepatic CYP enzymes drug metabolism
Summary
Over centuries the human immune system has evolved to battle against pathogenic microorganisms. Immunodeficiency, and infectious disease states could modulate drug metabolism and pharmacokinetics. The liver is an essential site of metabolism clearance [2]. Infection and inflammation are closely connected to the hepatic and extrahepatic metabolism of cytochromes P450 (CYPs), enzymes [2]. Cytochromes are proteins belonging in superfamilies containing heme as a cofactor. They are called hemoproteins and are used as substrates in enzymatic reactions. They are called CYPs. The term “P450” is issued from the spectrophotometric peak obtained at the maximum optic density of the enzyme (450 nm) when it is in its reduced state associated with carbon monoxide [2]
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