Akademik Veri Yönetim Sistemi
Tezin Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Pamukkale Üniversitesi, Fen-Edebiyat Fakültesi, Biyoloji Bölümü, Türkiye
Tezin Onay Tarihi: 2007
Tezin Dili: Türkçe
Öğrenci: Begüm Tütüncü
Danışman: Alaattin Şen
Özet:
Sulfite oxidase (SOX) is an essential enzyme in the pathway of the
oxidative degradation of sulfur containing amino acids. It protects
cells from toxicity of sulfite which has both endogenous and exogenous
provenances. SOX deficiency is an inborn error of the metabolism of
sulfated amino acids. Individuals affected with SOX deficiency most
commonly present in the neonatal period with intractable seizures,
characteristic dysmorphic features, and profound mental retardation.
Xenobiotic metabolism is carried out by large groups of
xenobiotic metabolizing enzymes (XME) that include the phase I
cytochrome P450s and phase II enzymes including various transferases.
XME play a dual role in xenobiotics metabolism. On one hand, they
transform compounds to more water soluble metabolites and thus enhance
their excretion. On the other hand, some of the intermediates arising
during this process become more toxic. Some factors like species, sex,
age, diet and genetic polymorphism alter XME levels and
causes considerable differences in biotransformation ability of
individuals, which is a problem faced by drug researchers interpreting
toxicological results to humans. The present project investigates the
role of SOX deficiency on xenobiotic metabolism, which is the first
report on changes of XME in SOX deficiency. In this study, male Wistar
albino rats, aged 3 months, were used. Three experimental groups, each
consisting of 30 rats, were formed; control group, SOX deficient group,
and the SOX deficient group treated with sulfite. Animals were housed
in groups of four to five rats in stainless steel cages at standard
conditions (24 ± 2°C and 50 ± 5% humidity) with a 12 h light?dark cycle
and fed ad libitum with standard rat chow and tap water. SOX deficiency
was produced in rats by the administration of a low molybdenum
diets (AIN 76a, Research Diets Inc, USA) with concurrent addition of 200
ppm tungsten to their drinking water. At the end of the experimental
period (7 weeks), livers, kidney, lung and small intestine were taken
and cytosolic and microsomal fractions were prepared. First, hepatic
SOX activity in deficient groups was measured to confirm SOX deficiency.
Then, Nnitrosodimethylamine N-demethylase (NDMA-ND), aniline
4-hydroxylase (A4H), erythromycin N-demethylase (ERND), aminopyrene
N-demethylase (APND), caffeine 3- N-demethylase (C3- ND),
ethoxyresorufin O-deethylase (EROD), penthoxyresorufin O-depenthylase
(PROD), benzyloxyresorufin O-debenzylase (BROD), methoxyresorufin
O-demethylase (MROD) and glutathione S-transferase (GST) activities were
determined to monitor XME activity changes in SOX deficiency. Our
results clearly demonstrated that SOX deficiency significantly
elevated A4H, ERND and NDMA-ND activities while decreasing EROD and GST
activities. No significant changes were observed with CN3D, MROD and
PROD activities. These alterations in XME can contribute to the varying
susceptibility and response of these individuals to different drugs
and/or therapeutics used for treatments