Kava or kava kava is a crop of the Pacific Islands. The name kava is from Tongan and Marquesan, meaning 'bitter'; other names for kava include ʻawa (Hawaiʻi), ʻava (Samoa), yaqona or yagona (Fiji), sakau (Pohnpei), seka (Kosrae), and malok or malogu. Kava is consumed for its sedating effects throughout the Pacific Ocean cultures of Polynesia, including Hawaii and Vanuatu, Melanesia, some parts of Micronesia, such as Pohnpei and Kosrae, and the Philippines.
Kavalactones are a class of lactone compounds found in kava roots and Alpinia zerumbet. Kavalactones are under research for potential to have various psychotropic effects, including anxiolytic and sedative/hypnotic activities.
Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.
Benzo[a]pyrene (BaP or B[a]P) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F). The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. The substance with the formula C20H12 is one of the benzopyrenes, formed by a benzene ring fused to pyrene. Its diol epoxide metabolites (more commonly known as BPDE) react with and bind to DNA, resulting in mutations and eventually cancer. It is listed as a Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma, was already known to be connected to soot.
Methylcholanthrene is a highly carcinogenic polycyclic aromatic hydrocarbon produced by burning organic compounds at very high temperatures. Methylcholanthrene is also known as 3-methylcholanthrene, 20-methylcholanthrene or the IUPAC name 3-methyl-1,2-dyhydrobenzo[j]aceanthrylene. The short notation often used is 3-MC or MCA. This compound forms pale yellow solid crystals when crystallized from benzene and ether. It has a melting point around 180 °C and its boiling point is around 280 °C at a pressure of 80 mmHg. Methylcholanthrene is used in laboratory studies of chemical carcinogenesis. It is an alkylated derivative of benz[a]anthracene and has a similar UV spectrum. The most common isomer is 3-methylcholanthrene, although the methyl group can occur in other places.
Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
Toxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as well as by abiotic chemical reactions. While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis. Different classes of enzymes, such as P450-monooxygenases, epoxide hydrolase, or acetyltransferases can catalyze the process in the cell, mostly in the liver.
Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.
The epoxyeicosatrienoic acids or EETs are signaling molecules formed within various types of cells by the metabolism of arachidonic acid by a specific subset of Cytochrome P450 enzymes termed cytochrome P450 epoxygenases. These nonclassic eicosanoids are generally short-lived, being rapidly converted from epoxides to less active or inactive dihydroxy-eicosatrienoic acids (diHETrEs) by a widely distributed cellular enzyme, Soluble epoxide hydrolase (sEH), also termed Epoxide hydrolase 2. The EETs consequently function as transiently acting, short-range hormones; that is, they work locally to regulate the function of the cells that produce them or of nearby cells. The EETs have been most studied in animal models where they show the ability to lower blood pressure possibly by a) stimulating arterial vasorelaxation and b) inhibiting the kidney's retention of salts and water to decrease intravascular blood volume. In these models, EETs prevent arterial occlusive diseases such as heart attacks and brain strokes not only by their anti-hypertension action but possibly also by their anti-inflammatory effects on blood vessels, their inhibition of platelet activation and thereby blood clotting, and/or their promotion of pro-fibrinolytic removal of blood clots. With respect to their effects on the heart, the EETs are often termed cardio-protective. Beyond these cardiovascular actions that may prevent various cardiovascular diseases, studies have implicated the EETs in the pathological growth of certain types of cancer and in the physiological and possibly pathological perception of neuropathic pain. While studies to date imply that the EETs, EET-forming epoxygenases, and EET-inactivating sEH can be manipulated to control a wide range of human diseases, clinical studies have yet to prove this. Determination of the role of the EETS in human diseases is made particularly difficult because of the large number of EET-forming epoxygenases, large number of epoxygenase substrates other than arachidonic acid, and the large number of activities, some of which may be pathological or injurious, that the EETs possess.
Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.
Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.
Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.
A benzopyrene is an organic compound with the formula C20H12. Structurally speaking, the colorless isomers of benzopyrene are pentacyclic hydrocarbons and are fusion products of pyrene and a phenylene group. Two isomeric species of benzopyrene are benzo[a]pyrene and the less common benzo[e]pyrene. They belong to the chemical class of polycyclic aromatic hydrocarbons.
Dihydromethysticin is one of the six major kavalactones found in the kava plant.
Benzo[c]fluorene is a polycyclic aromatic hydrocarbon (PAH) with mutagenic activity. It is a component of coal tar, cigarette smoke and smog and thought to be a major contributor to its carcinogenic properties. The mutagenicity of benzo[c]fluorene is mainly attributed to formation of metabolites that are reactive and capable of forming DNA adducts. According to the KEGG it is a group 3 carcinogen. Other names for benzo[c]fluorene are 7H-benzo[c]fluorene, 3,4-benzofluorene, and NSC 89264.
(+)-Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide is an organic compound with molecular formula C20H14O3. It is a metabolite and derivative of benzo[a]pyrene (found in tobacco smoke) as a result of oxidation to include hydroxyl and epoxide functionalities. (+)-Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide binds to the N2 atom of a guanine nucleobase in DNA, distorting the double helix structure by intercalation of the pyrene moiety between base pairs through π-stacking. The carcinogenic properties of tobacco smoking are attributed in part to this compound binding and inactivating the tumor suppression ability of certain genes, leading to genetic mutations and potentially to cancer.
