Plant-Based Adjunct Therapy for Tuberculosis
Namrita Lall in Medicinal Plants for Cosmetics, Health and Diseases, 2022
Cytochrome P450 enzymes are heme-containing proteins found in humans and bacteria. Discovery and characterization of P450 in liver extracts occurred in the 1950s (Garfinkel, 1958; Klingenberg, 1958). The pigment displayed the ability to absorb maximally at 450 nm when reduced with carbon monoxide present. Hence, the term P450 from the indication ‘pigment-450.’ Expression of P450 enzymes occurs throughout nature. In mammals, about one-third of the P450 enzymes are expressed in the liver and play a role in the degradation of numerous xenobiotic compounds (Furge and Guengerich, 2006). Cytochrome P450 pathways are categorized according to similar gene sequences and assigned a family member (e.g. CYP1, CYP2) and a subfamily letter (e.g. CYP1A, CYP2C) and further differentiated by a number for the isoform or individual enzyme (e.g. CYP1A1, CYP2C9). Drugs that undergo common pathways have the potential for drug–drug interactions (McDonnell et al., 2013, Nelson, 2009).
Occupational Cancer
Peter G. Shields in Cancer Risk Assessment, 2005
An example of markers of risk is the relationship of polymorphic variants of cytochrome P450 in the metabolic activation of precarcinogens. Many Phase I P450 enzymes bioactivate carcinogens, whereas Phase II enzymes participate in the deactivation process. Both the CYP1A1 and CYP2E1 variants of Phase I P450 enzymes are involved in the metabolism of many suspected and established carcinogens. Since genetic polymorphisms have been identified for both Phase I and Phase II enzymes, risk assessments could be enhanced if polymorphisms in both enzyme categories are considered as biomarkers for susceptibility to cancer (30). Genetic and molecular epidemiology research involving the use of biomarkers also raises ethical questions, related to the potential for such information to be used for discriminatory purposes (31–33).
Bioavailability of Herbal Drugs
Ravindra Kumar Pandey, Shiv Shankar Shukla, Amber Vyas, Vishal Jain, Parag Jain, Shailendra Saraf in Fingerprinting Analysis and Quality Control Methods of Herbal Medicines, 2018
The following are the chief mechanisms via which the various bioenhancers exert their bioavailability by enhancing properties on the drug molecules: By enhancing the absorption of orally administered drugs from the gastrointestinal tract by an increase in blood supply (Dudhatra et al., 2012).By modulating the active transporters located in various locations, for example: P-glycoprotein (P-gp) is an efflux pump which pumps out a drug and prevents it from reaching the target site. Bioenhancers in such a case act by inhibiting the P-gp.Decreasing the elimination process thereby extending the sojourn of a drug in the body. Inhibiting the drug metabolizing enzymes such as CYP 3A4, CYP1A1, CYP1B2, and CYP2E1 in the liver, gut, lungs, and various other locations. This will, in addition, help to overcome the first pass effect of administered drugs.Inhibiting the renal clearance by preventing glomerular filtration and active tubular secretion by inhibiting P-gp and facilitating passive tubular reabsorption. Sometimes biliary clearance is also affected by inhibiting the uridine diphosphate (UDP) glucuronyl transferase enzyme which conjugates and inactivates the drug (Kang et al., 2009).
Particulate matter less than 10 μm (PM10) activates cancer related genes in lung epithelial cells
Published in Inhalation Toxicology, 2020
Daeun Kang, In Beom Jung, Su Yel Lee, Se Jin Park, Sun Jung Kwon, Dong Ho Park, Ji Woong Son
Among the top 10 genes upregulated and downregulated genes in our study, those whose NGS and qRT-PCR results match are the CYP1A1, CYP1B1, LINC01816, and BPIFA2, as mentioned above. CYP1A1 and CYP1B1 encode a member of the cytochrome P450 superfamily of enzymes. The expression of CYP1A1 is induced by some polycyclic aromatic hydrocarbons (PAHs) or tobacco smoke, and they can metabolize some PAHs to carcinogenic intermediates (Shimada and Fujii-Kuriyama 2004). The expression can be regulated by heavy metal (Korashy and El-Kadi 2005; Anwar-Mohamed et al. 2009). There are many reports that CYP1A1 is linked to lung cancer. CYP1A1 can initiate carcinogenesis in lung cells through PAH metabolism (Uppstad et al. 2010). CYP1A1 plays an important role in lung DNA adduct formation and causes a higher susceptibility to lung cancer among women than men (Mollerup et al. 2006). Przygodzki et al. (1998) reported that CYP1A1 activation contributes to lung cancer via p53 inactivation. Some studies show that CYP1A1 polymorphism contributes to lung cancer susceptibility (Taioli et al. 2003; Ji et al. 2012).
CYP1A1 gene (6235T<C) polymorphism as a risk factor for polycystic ovarian syndrome among Egyptian women
Published in Human Fertility, 2020
Nervana Bayoumy, Mohamed El-Shabrawi, Soha Younes, Khaled Atwa
The CYP1A1 gene encodes a member of the cytochrome P450 enzyme superfamily and is located at 15q22-q24 (Lanca et al., 2002). Cytochrome P450 proteins (monooxygenases) are involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The expression of these proteins is induced by some of the products of cigarette smoking, including polycyclic aromatic hydrocarbons (PAHs). PAHs were found to be carcinogenic intermediates and are considered to be associated with lung cancer (Loft et al., 2005). Also, they have been hypothesized to affect folliculogenesis and oogenesis. CYP1A1 is involved in oestradiol oxidation to 2-OH and 4-OH catechol oestrogens in both ovarian and extra-ovarian tissues. These catechol oestrogens were found to be more risky for granulosa cell replication and follicular growth. Also, CYP1A1 was found to activate many environmental procarcinogens like benzo[a]pyrene and CYP1A1 enzymes can be induced by other endocrine disruptors such as dioxins and organochlorines, causing aggravation of these changes. These mechanisms can cause abnormal folliculogenesis and the formation of cystic ovaries by causing cell damage and toxicity to the oocyte and granulosa cell (Neal, Zhu, Holloway, & Foster, 2007; Shen, Li, Hu, Liu, & Song, 2013).
Structure–activity relationship and in vitro inhibition of human cytochrome CYP2A6 and CYP2A13 by flavonoids
Published in Xenobiotica, 2020
Supattra Boonruang, Khanistha Prakobsri, Phisit Pouyfung, Aruna Prasopthum, Pornpimol Rongnoparut, Songklod Sarapusit
Flavonoids are a large diverse group of phytochemicals ubiquitously distributed in all foods of plant origin. These derivatives have been recognized to possess a broad spectrum of biological activity such as anti-allergic, anti-inflammatory, anti-oxidative, anti-microbial, anti-tumorigenic, and antimutagenic activities, thus affecting a number of diseases including cancer, heart disease, and bone loss in humans (Arct & Pytkowska, 2008; Havsteen, 2002; Kale et al., 2008; Khlebnikov et al., 2007; Seyoum et al., 2006; Shimada, 2017; Walle et al., 2007; Zhang et al., 2005). Moreover, modulation of cytochrome P450 (CYP) activity by flavonoids has become an area of interest because flavonoids may act as either an inhibitor or inducer of various human CYPs and affects drug metabolism such as CYP1A1 (Zhai et al., 1998), CYP1A2 (Lautraite et al., 2002), CYP1B1 (Doostdar et al., 2000), and CYP3A4 (Chan et al., 1998).
Related Knowledge Centers
- Drug Metabolism
- Macrolide
- Protein
- Theophylline
- Xenobiotic
- Flavonoid
- Cytochrome P450
- Gene
- Hesperetin
- Quinolone Antibiotic