Cytochrome P450 dependent drug metabolism in diabetic rabbits

Download
2003
Arslan, Şevki
Diabetus mellitus is a metabolic disorder of carbohydrate, fat and protein metabolism as a result of insulin deficiency or diminished tissue response to insulin. In this study, diabetes was induced in rabbits experimentally by intravenous injection of 100mg/kg alloxan. Injection of a single dose of alloxan to rabbits induced diabetus mellitus as it was understood from 4-fold increase in the blood glucose level and also 2-fold increase in blood urea concentrations. The influence of diabetus mellitus on cytochrome P450 levels, microsomal cytochrome P450 dependent drug metabolizing enzymes and on the biomarkers used to measure chemical-induced toxicity including AST, ALT and LDH were examined in rabbit liver, kidney and lung.Results obtained in this study showed that diabetus mellitus elevated microsomal cytochrome P450 contents of liver and kidney by 1.3- and 2-fold, respectively. Induction of the cytochrome P450 isozymes was observed with the high intensity bands having Mr between 51 000 Da and 53 000 Da and 45 000 Da to 48 000 Da in the SDS-PAGE profiles of liver microsomes obtained from the diabetic rabbits. However, the changes in kidney and lung microsomal protein patterns of diabetic rabbits compared to control animals were not so pronounced as observed in rabbit liver. Induction of diabetus mellitus caused 1.67-, 2.36- and 1.32-fold increases in aniline 4-hydroxylation rates of liver, kidney and lung microsomes, respectively. Induction of experimental diabetes enhanced hydroxylation rates of /Miitrophenol by liver, kidney and lung microsomes about 1.8-, 2.3- and 1.32-fold, respectively. NDMA N- demethylase activity was enhanced by diabetes in all three of these organs. (1.98-fold in liver, 1.85-fold in kidney, 1.35-fold in lung). Induction of diabetes in rabbits caused an increase of the P4502E1 level of microsomes and this was reflected in increased rate of metabolism of aniline, p-nitrophenol and NDMA. In this study, blood serum triglyceride, creatinine, urea and cholesterol concentrations were determined in control and diabetic rabbits. In addition, the effects of diabetes on transaminases (ALT and AST) and lactate dehydrogenase enzyme activities of rabbit blood serum and soluble fractions of rabbit liver, kidney and lung were investigated. Histological studies were carried out in control and diabetic rabbit liver and kidney tissue samples to investigate any tissue degeneration (necrosis). This is the first time induction of cytochrome P450 dependent monooxygenases has been reported for liver, kidney and lung microsomes of diabetic rabbits.

Suggestions

MATERNAL OBESITY EFFECT ON OFFSPRING PANCREATIC ENDOCRINE CELLS: INVESTIGATION OF THE CELL TRANSDIFFERENTIATION PROFILE THAT CAUSES DIABETIC SUSCEPTIBILITY
FEYAT, MEHMET SEDAT; Yanık, Tülin; Özçubukçu, Salih; Department of Biotechnology (2022-6-13)
In general, Type 2 Diabetes (T2D) is a disease characterized by impaired functioning of pancreatic beta cells and progressive insulin hormone deficiency progressively in combination with physiologically ongoing insulin resistance. In the later stages of the disease, beta cell dysfunction is defined as beta cell death and a decrease in functional cell count. It is a common clinical finding in patients with T2D that therapeutic drugs lowering insulin resistance and diet in the course of the disease treatment ...
Biophysical characterization and diagnosis of obesity from adipose tissue by fourier transform infrared spectroscopy and imaging
Küçük Baloğlu, Fatma; Severcan, Feride; Department of Biology (2017)
Obesity is a heterogeneous disorder originating from the enlargement of visceral (VAT) and subcutaneous (SCAT) adipose tissue mass in the body and this process usually results in disturbed glucose and lipid metabolism. The first part of this study aimed to characterize and compare VAT and SCAT with regard to biomolecular content and also investigate transdifferentiation between white and brown adipocytes. Regarding this aim, Fourier transform infrared (FTIR) microspectroscopy and uncoupling protein 1 (UCP1)...
The effects of streptozotocin induced-diabetes on rat testes and the recovery role of vitamin c
Güldağ, Damla; Severcan, Feride; Department of Biology (2012)
Type I Diabetes is a multisystem disease having both biochemical and structural consequences. It causes alterations in carbohydrate, protein, and fat metabolisms due to hyperglycemia. Type I diabetes is also correlated with increased formation of free radicals and decreased levels of antioxidant potential. Lower endogeneous antioxidant amounts and elevated lipid peroxidation levels in diabetes constitute the basis of risk factors for the development of diabetic complications. These complications lead to irr...
The effects of high cholesterol/high fat diet on endoplasmic reticulum stress and neuronal dysfunction in the hippocampus and cerebral cortex of APOE-/- MICE
Mengi, Naz; Yanık, Tülin; Department of Molecular Biology and Genetics (2019)
Hyperlipidemia is an obesity-associated lipid metabolism disorder with high serum total cholesterol (TC) levels and is known to be a risk factor for neurodegenerative diseases. High-fat diet (HFD) induced elevated inflammation levels accompanied by increased levels of apoptosis markers and decreased levels of synaptic proteins in the hippocampus points out a possible neuronal loss. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway is activated by endoplasmic reticulum (ER) stress. The acti...
The effect of diabetes mellitus on rat skeletal extensor digitorum longus muscle tissue: An FTIR study
Bozkurt, Ozlem; Bilgin, Mehmet Dincer; Severcan, Feride (Hindawi Limited, 2007)
Diabetes mellitus (DM) is a chronic disorder of carbohydrate, fat and protein metabolism, which is characterized by a defective insulin secretory response. Skeletal muscle takes role in determination of carbohydrate and lipid metabolism, therefore; it is one of the target tissues of diabetes. Herein this study, application of Fourier Transform Infrared (FTIR) spectroscopy in diabetic skeletal Extensor Digitorum Longus (EDL) muscle tissues will be presented which highlight the promise of this technique in me...
Citation Formats
Ş. Arslan, “Cytochrome P450 dependent drug metabolism in diabetic rabbits,” M.S. - Master of Science, Middle East Technical University, 2003.