7-Ethoxyresorufin

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that is encoded by human CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes. CYP1A1 is involved in phase I xenobiotic and drug metabolism. CYP1A1 is inhibited by fluoroquinolones and macrolides and induced by aromatic hydrocarbons. 7-Ethoxyresorufin is a specific subtrate of CYP1A.

In vitro: 7-Ethoxyresorufin (2-10 microM), a substrate for cytochrome P450, which binds to the heme moiety of the enzyme, reduced responses to acetylcholine concentration-dependently but not the other agonists indicating an effect on nitric oxide synthesis although neither affected the conversion of L-arginine to L-citrulline [1].

In vivo: Activities of CYP1A (7-ethoxyresorufin) in the liver was determined for comparative purposes. In mice, LPS depressed CYP2A5 at low doses but not at doses that increased pro-inflammatory cytokines and NO serum levels, and depressed CYP1A activity. Blockade of proinflammatory cytokines extended down-regulation of CYP2A5 while not affecting LPS-induced depression of CYP1A [2].

Clinical trial: Cytochrome P-450 enzyme activities of 7-ethoxyresorufin O-deethylase (ERDE) was measured in human liver needle biopsy samples from smokers and non-smokers. ERDE activity was significantly elevated in the livers of cigarette smokers. No correlation was observed between plasma cotinine concentration and ERDE activity [3].

References:
[1] Oyekan AO, McGiff JC, Rosencrantz-Weiss P, Quilley J.  Relaxant responses of rabbit aorta: influence of cytochrome P450 inhibitors. J Pharmacol Exp Ther. 1994 Jan;268(1):262-9.
[2] De-Oliveira AC, Poça KS, Totino PR, Paumgartten FJ.  Modulation of cytochrome P450 2A5 activity by lipopolysaccharide: low-dose effects and non-monotonic dose-response relationship. PLoS One. 2015 Jan 30;10(1):e0117842.
[3] Pelkonen O, Pasanen M, Kuha H, Gachalyi B, Kairaluoma M, Sotaniemi EA, Park SS, Friedman FK, Gelboin HV.  The effect of cigarette smoking on 7-ethoxyresorufin O-deethylase and other monooxygenase activities in human liver: analyses with monoclonal antibodies. Br J Clin Pharmacol. 1986 Aug;22(2):125-34.


Impaired dacarbazine activation and 7-ethoxyresorufin deethylation in vitro by polymorphic variants of CYP1A1 and CYP1A2: implications for cancer therapy.[Pubmed:27428168]

Pharmacogenet Genomics. 2016 Oct;26(10):453-61.

OBJECTIVES: To extend our understanding of how interindividual variability mediates the efficacy of cancer treatment. MATERIALS AND METHODS: The kinetics of dacarbazine (DTIC) N-demethylation by the most frequent polymorphic variants of CYP1A1 (T461N, I462V) and CYP1A2 (F186L, D348N, I386F, R431W, R456H) were characterized, along with kinetic parameters for the O-deethylation of the prototypic CYP1A substrate 7-Ethoxyresorufin, using recombinant protein expression and high-performance liquid chromatographic techniques. RESULTS: A reduction of approximately 30% in the catalytic efficiencies (measured as in-vitro intrinsic clearance, CLint) was observed for DTIC N-demethylation by the two CYP1A1 variants relative to wild type. Although a modest increase in the CLint value for DTIC N-demethylation was observed for the CYP1A2 D348N variant relative to the wild type, the CLint for the F186L variant was reduced and the I386F, R431W, and R456H variants all showed loss of catalytic function. CONCLUSION: Comparison of the kinetic data for DTIC N-demethylation and 7-Ethoxyresorufin O-deethylation indicated that alterations in the kinetic parameters (Km, Vmax, CLint) observed with each of the CYP1A1 and CYP1A2 polymorphic variants were substrate dependent. These data indicate that cancer patients treated with DTIC who possess any of the CYP1A1-T461N and I462V variants or the CYP1A2-F186L, D348N, I386F, R431W, and R456H variants are likely to have decreased prodrug activation, and hence may respond less favorably to DTIC treatment compared with individuals with wild-type CYP1A alleles.

In vitro inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and p-nitrophenol hydroxylase (PNPH) activities by sesamin in hepatic microsomes from two fish species.[Pubmed:23065221]

Mol Biol Rep. 2013 Jan;40(1):457-62.

In the present study, we investigated the effect of sesamin on CYP1A (7-Ethoxyresorufin-O-deethylase, EROD) and CYP2E1-like activities (p-nitrophenol hydroxylase, PNPH) in hepatic microsomes obtained from Atlantic salmon (Salmo salar) and common carp (Cyprinus carpio). Addition of sesamin to the incubations in a concentration range from 1 to 200 muM decreased the activities of EROD and PNPH in a concentration dependent manner. It is likely that the inhibition of EROD was mechanism-based as demonstrated by the decrease in the IC50 value from 5.9 to 3.2 muM for A. salmon and from 7.9 to 3.0 muM for common carp when 5 min pre-incubation step was included. Similarly, PNPH activity was inhibited by sesamin with a decrease in the IC50 values from 61.7 to 15.2 muM for A. salmon and from 194.3 to 20.7 muM for common carp. Thus, our results indicated that sesamin can act as a mechanism-based inhibitor of EROD and PNPH activity with similar degree of inhibition in both fish species. More importantly, the inhibition of CYP1A, in addition to being mechanism-based, was competitive with K(i) value of 5.3 muM.

The responses of the hepatosomatic index (HSI), 7-ethoxyresorufin-O-deethylase (EROD) activity and glutathione-S-transferase (GST) activity in sea bass (Dicentrarchus labrax, Linnaeus 1758) caged at a polluted site: implications for their use in environmental risk assessment.[Pubmed:23644668]

Environ Monit Assess. 2013 Nov;185(11):9009-18.

The present study investigates the response of three hepatic biomarkers in adult sea bass (Dicentrarchus labrax, Linnaeus 1758) caged at a wastewater outlet of an oil refinery with fish caged at a pristine site used as controls. The biomarkers that were investigated were the hepatosomatic index (HSI), 7-Ethoxyresorufin-O-deethylase (EROD) activity and glutathione-S-transferase (GST) activity. In addition, we have measured the levels of polycyclic aromatic hydrocarbons (PAHs) and selected heavy metals (lead, cadmium, mercury, copper and zinc) in sediment samples at the polluted site. Although the polluted site had high environmental levels of PAHs and heavy metals, there was no difference in hepatic EROD activity and HSI between fish caged at the polluted site and controls. On the other hand, GST activity was significantly lower in fish caged at the polluted site compared to controls. Our results point out that the studied biomarkers have limited use in environmental risk assessment studies, at least when caged adult sea bass is used as the sentinel species and complex toxicant mixtures are involved.

Assessment of cytotoxicity, genotoxicity and 7-ethoxyresorufin-O-deethylase (EROD) induction in sediment extracts from New Zealand urban estuaries.[Pubmed:28083773]

Ecotoxicology. 2017 Mar;26(2):211-226.

Sediments represent a major sink for contaminants resulting from industrial and agricultural activities - especially lipophilic substances. This study exclusively used in vitro methodologies to characterize specific toxicity effects of contaminants in sediment extracts from two urban New Zealand estuaries. Sediment extracts were prepared and tested for a range of biological endpoints. The micronucleus and comet assays in V79 cells were used to assess genotoxicity. Induction of 7-Ethoxyresorufin-O-deethylase in piscine RTL-W1 cells was determined to estimate dioxin-like toxicity. Cytotoxic potentials were analyzed by neutral red uptake and MTT reduction. There was evidence of strong dioxin-like toxicity and moderate cytotoxicity. Genotoxicity was distinct in the micronucleus assay, but low in the comet assay. The results indicate the presence of chemicals in the sediments with the potential to pose a risk through multiple mechanisms of toxicity, the identities and amounts of which will be disclosed in a parallel study alongside with in vivo toxicity data.