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

Date

2007-01-01

Author

Arinc, Emel
Arslan, Sevki
Bozcaarmutlu, Azra
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

127
views

0
downloads

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 immunochemical detection on Western blots in the lung and kidney microsomes of rabbits. In parallel to CYP2EI induction, aniline 4-hydroxylase and p-nitrophenol hydroxylase activities were markedly increased in diabetic rabbit lung and kidney. CYP2B4 and CYP2E1 dependent drug metabolism did not show any tissue variation in diabetic rabbit. These findings are in contrast to those of rats, mice and hamster. The results of the present work, in combination with those of the previous work [Arinc, E., Arslan, S., Adali, O., 2005. Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver. Arch. Toxicol. 79, 427433], indicate the existence of species-dependent response of GYP-dependent drug metabolizing enzymes to diabetes. A procarcinogen and food contaminant, N-nitrosodimethylamine (NDMA), is converted to its carcinogenic form after it is activated with NDMA N-demethylase. In the current study, a statistically significant increase of liver, kidney and lung NDMA N-demethylase activity associated with CYP2E1 was shown in diabetic rabbit. Thus, it is expected that, the risk of nitrosamine induced carcinogenesis will be greater in liver, kidney and lung of the diabetic subjects.

Subject Keywords

Toxicology, Food Science, General Medicine

URI

https://hdl.handle.net/11511/47121

Journal

FOOD AND CHEMICAL TOXICOLOGY

DOI

https://doi.org/10.1016/j.fct.2006.07.026

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver Arinc, E; Arslan, S; Adalı, Orhan (Springer Science and Business Media LLC, 2005-08-01) 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 activi...
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...
Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet (Liza saliens) Bozcaarmutlu, Azra; Arinc, Emel (Elsevier BV, 2007-04-01) Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg(+2), Cd(+2), Ni(+2), Cr(+3) and Zn(+2) ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn(+2). At 50 mu M metal concentration, Hg(+2...
Effects of early postnatal alcohol exposure on the developing retinogeniculate projections in C57BL/6 mice DURSUN, İLKNUR; Jakubowska-Dogru, Ewa; Elibol-Can, Birsen; van der List, Deborah; Chapman, Barbara; Qi, Lihong; Berman, Robert F. (Elsevier BV, 2013-05-01) Previous studies on the adverse effects of perinatal exposure to ethanol (EtOH) on the developing visual system mainly focused on retinal and optic nerve morphology. The aim of the present study was to investigate whether earlier reported retinal and optic nerve changes are accompanied by anomalies in eye-specific fiber segregation in the dorsal lateral geniculate nucleus (dLGN). C57BL/6 mice pups were exposed to ethanol by intragastric intubation at either 3 or 4 g/kg from postnatal days (PD) 3-10, the thi...
Effect of vitamin C and lipoic acid on streptozotocin-induced diabetes gene expression: mRNA and protein expressions of Cu-ZnSOD and catalase Sadi, Goekhan; Yilmaz, Oekkes; Güray, Nülüfer Tülün (Springer Science and Business Media LLC, 2008-02-01) The involvement of oxidative stress in the pathogenesis of diabetes mellitus has been confirmed by numerous studies. In this study, the expression of two antioxidant enzymes, superoxide dismutase (SOD), and catalase which are involved in the detoxification of reactive oxygen species was studied in the streptozotocin-induced diabetic rat liver tissues. The enzyme assays showed a significant decrease in both enzymes activities compared to control animals. The RT-PCR and Western-blot analysis results demonstra...

Citation Formats

E. Arinc, S. Arslan, A. Bozcaarmutlu, and O. Adalı, “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,” FOOD AND CHEMICAL TOXICOLOGY, pp. 107–118, 2007, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/47121.