Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver

Date

2005-08-01

Author

Arinc, E
Arslan, S
Adalı, Orhan

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

222
views

0
downloads

The effects of diabetes on cytochrome P450 (CYP)-dependent drug metabolizing enzymes are yet to be clarified. The most widely used animals in these studies have been rats, and information on the effects of diabetes on rabbit liver drug metabolizing enzymes have been unavailable until now. In this study, for the first time, a significant induction of liver CYP2E1 is demonstrated via immunoblot analysis in alloxan-induced rabbits. The CYP2E1 content of diabetic microsomes was highly correlated with the activities of liver aniline 4-hydroxylase (r=0.82, p < 0.05), and p-nitrophenol hydroxylase (r=0.86, p < 0.01), and diabetes increased the activities of the enzymes associated with CYP2E1. The activities of aniline 4-hydroxylase and p-nitrophenol hydroxylase were significantly increased by 1.7 and 1.8-fold, respectively compared to those of control rabbits. In marked contrast, diabetes had no effect on the protein levels of CYP2B4 as determined by immunoblotting and on benzphetamine N-demethylase activity, which is known to be specifically metabolized by CYP2B4 in rabbit liver. The present study demonstrates that diabetes increases the activities of CYP2E1 and associated enzymes but does not change the activity levels of CYP2B4 and associated enzymes in diabetic rabbits. These findings are in contrast to those of mice, hamsters and rats, and that suggest the presence of species-dependent responses of CYP-dependent drug metabolizing enzymes to diabetes.

Subject Keywords

Toxicology, Health, Toxicology and Mutagenesis, General Medicine

URI

https://hdl.handle.net/11511/43974

Journal

ARCHIVES OF TOXICOLOGY

DOI

https://doi.org/10.1007/s00204-005-0654-8

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung Arinc, Emel; Arslan, Sevki; Bozcaarmutlu, Azra; Adalı, Orhan (Elsevier BV, 2007-01-01) There are limited number of studies regarding the influence of diabetes on the regulation of cytochrome P450s and associated drug metabolizing enzyme activities especially in extrahepatic tissues such as kidney. However, there is almost no such study in lung. Alloxan-induced diabetes did not change CYP2B4 expression as measured with immunoblot analysis and associated enzyme, benzphetamine N-demethylase, activity in rabbit kidney and lung. Induction of cytochrome P4502E1 by diabetes was identified by immunoc...
STIMULATORY EFFECTS OF BENZENE ON RABBIT LIVER AND KIDNEY MICROSOMAL CYTOCHROME-P-450 DEPENDENT DRUG-METABOLIZING-ENZYMES ARINC, E; Adalı, Orhan; ISCAN, M; Güray, Nülüfer Tülün (Springer Science and Business Media LLC, 1991-01-01) Treatment of rabbits with benzene (880 mg/kg/day), s.c. for 3 consecutive days, caused 3.8- and 5.7-fold increases in aniline 4-hydroxylation rates of liver and kidney microsomes, respectively. Benzene treatment markedly enhanced hydroxylation rates of p-nitrophenol by liver and kidney by 7.2- and 4.2-fold, respectively. Both of these enzymes are associated with cytochrome P-450 LM3a. In contrast, the activity of benzphetamine N-demethylase, associated with P-450 LM2, was not altered significantly in eit...
Effects of benzene on liver, kidney and lung cyp1a, cyp2b4, cyp2e1 and cyp3a6 mrna, protein level, and drug metabolizing enzyme activities and toxicity in diabetic rabbits Arslan, Şevki; Arınç, Emel; Department of Biochemistry (2008) The effects of diabetes on cytochrome P450 dependent drug metabolizing enzymes have not to be clarified yet. The most widely used animals in these studies have been rats, and information regarding the effects of diabetes on cytochrome P450 dependent procarcinogen/carcinogen metabolism in rabbits is limited. In the present study, we investigated, for the first time, the influence of benzene on liver, kidney and lung microsomal cytochrome P450 dependent drug metabolizing enzyme activities, protein and mRNA le...
Association between polymorphisms of EPHX1 and XRCC1 genes and the risk of childhood acute lymphoblastic leukemia TÜMER, TUĞBA; Sahin, Gurses; Arinc, Emel (Springer Science and Business Media LLC, 2012-03-01) Microsomal epoxide hydrolase, EPHX1, plays a central role in the detoxification of potentially genotoxic epoxide intermediates. In this study, we firstly aimed to investigate the relationship between EPHX1 Tyr113His and His139Arg variants, and the risk of incidence of childhood acute lymphoblastic leukemia (ALL) in Turkish population, comprised of 190 healthy controls and 167 ALL patients. In exon 3 Tyr113His polymorphism, 113His/His homozygous mutant genotype with slow activity was 18.6% in ALL patients an...
Effects of Early Postnatal Exposure to Ethanol on Retinal Ganglion Cell Morphology and Numbers of Neurons in the Dorsolateral Geniculate in Mice Dursun, Ilknur; Jakubowska-Dogru, Ewa; van der List, Deborah; Liets, Lauren C.; Coombs, Julie L.; Berman, Robert F. (Wiley, 2011-11-01) Background: The adverse effects of fetal and early postnatal ethanol intoxication on peripheral organs and the central nervous system are well documented. Ocular defects have also been reported in about 90% of children with fetal alcohol syndrome, including microphthalmia, loss of neurons in the retinal ganglion cell (RGC) layer, optic nerve hypoplasia, and dysmyelination. However, little is known about perinatal ethanol effects on retinal cell morphology. Examination of the potential toxic effects of alcoh...

Citation Formats

E. Arinc, S. Arslan, and O. Adalı, “Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver,” ARCHIVES OF TOXICOLOGY, pp. 427–433, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/43974.