Biochanin A and formononetin are abundant in legumes. These proestrogenic isoflavones can be converted by 4'-O-demethylation to the more potent phytoestrogens genistein and daidzein. Incubation of biochanin A or formononetin with human liver microsomes resulted in 4'-O-demethylation and the production of additional metabolites. Three new hydroxylated formononetin derivatives, 6,7-dihydroxy-4'-methoxyisoflavone, 7,8-dihydroxy-4'-methoxyisoflavone, and 7,3'-dihydroxy-4'-methoxyisoflavone, were isolated and characterized. We surveyed the O-demethylase competence of cytochrome P450 isoforms found in human liver. Human cytochrome P450 isoforms 1A2, 2E1, 2C9*1, 2C19, and 2D6*1 catalyzed biochanin A consumption and genistein production. Human cytochrome P450 isoforms 1A2, 2C9*1, 2A6, 2D6*1, and 2C19 catalyzed formononetin consumption and daidzein production. These isoforms also generated other hydroxylated metabolites. Although O-demethylation of isoflavones has been attributed to metabolism by gut microflora, our study demonstrates that human hepatic microsomal enzymes can perform the same transformation and may play a key role in the conversion of 4'-O-methylated isoflavones to more potent phytoestrogens.
The human melanocytes of the skin, hair, eyes, inner ears, and covering of the brain provide physiologic functions important in organ development and maintenance. Melanocytes develop from embryonic neural crest progenitors and share certain traits with other neural crest derivatives found in the adrenal medulla and peripheral nervous system. The distinctive metabolic feature of melanocytes is the synthesis of melanin pigments from tyrosine and cysteine precursors involving over 100 gene products. These complex biochemical mechanisms create inherent liabilities for melanocytic cells if intracellular systems necessary for compartmentalization, detoxification, or repair are compromised. Melanocyte disorders may involve pigmentation, sensory functions, autoimmunity, or malignancy. Environmental factors such as ultraviolet radiation and chemical exposures, combined with heritable traits, represent the principal hazards associated with melanocyte disorders.
Ricin is a plant toxin with high bioterrorism potential due to its natural abundance and potency in inducing cell death. Early detection of the active toxin is essential for developing appropriate countermeasures. Here we review concepts for designing ricin detection methods, including mechanism of action of the toxin, advantages and disadvantages of current detection assays, and perspectives on the future development of rapid and reliable methods for detecting ricin in environmental samples.
Sunlight is a known human carcinogen. Many cosmetics contain retinoid-based compounds, such as retinyl palmitate (RP), either to protect the skin or to stimulate skin responses that will correct skin damaged by sunlight. However, little is known about the photodecomposition of some retinoids and the toxicity of these retinoids and their sunlight-induced photodecomposition products on skin. Thus, studies are required to test whether topical application of retinoids enhances the phototoxicity and photocarcinogenicity of sunlight and UV light. Mechanistic studies are needed to provide insight into the disposition of retinoids in vitro and on the skin, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied retinoids in the presence of UV light. This paper reports the update information and our experimental results on photostability, photoreactions, and phototoxicity of the natural retinoids including retinol (ROH), retinal, retinoid acid (RA), retinyl acetate, and RP (Figure 1).
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