The Effects of Amoxicillin and Vancomycin Hydrochloride Hydrate on Glutathione S-Transferase Enzyme Activity: An in vitro study

Yıl 2018, , 141 - 148, 30.06.2018

Fikret Türkan , Mehmet Nuri Atalar

https://doi.org/10.21597/jist.428354

Cited By: 6

Öz

Glutathione S-transferase (GST) enzymes detoxify a broad spectrum of xenobiotics, including

chemotherapeutic drugs, environmental carcinogens, and endogenous molecules. Glutathione transferases catalyze

the conversion of some metabolites into less toxic substances. Phase II reactions, which often result in detoxification,

are conjugation reactions of glutathione through GST enzymes that protect the organism from the attacks of highly

reactive electrophilic substances. Since the GST enzyme can metabolize toxic exogenous compounds, it has been

extensively investigated in mammals. In this study, the GST enzyme was purified in human erythrocytes with a

specific activity of 5.56 EU mg-1 protein and a yield of 2316.0 fold with 65% efficienc. SDS-polyacrylamide gel

electrophoresis was performed to check the purity of the purified enzyme and the molecular mass was determined

to be about 26 kDa. The IC50 and Ki values for amoxycillin and vancomycin hydrochloride drugs on the purified

GST enzyme were calculated and the type of inhibition was determined. As a result of the inhibition studies, we

observed that these antibiotics inhibited the GST enzyme at low doses.

Anahtar Kelimeler

Amoxicillin, vancomycin hydrochloride hydrate, glutathione s-transferase

Glutatyon S-Transferaz Enzim Aktivitesi Üzerine Amoksilin ve Vankomisin Hidroklorid Hidratın Etkisi: Bir in vitro çalışma

Öz

Glutatyon S-transferaz enzimleri kemoterapik ilaçlar, çevresel karsinojenler, endojen moleküller olmak

üzere ksenobiyotiklerin geniş bir spektrumunu detoksifiye ederler. Glutatyon transferazlar, bazı metabolitleri daha

az toksik olan maddelere dönüşmesini katalize eder. Çoğunlukla detoksifikasyonla sonuçlanan faz II reaksiyonları

arasında organizmayı son derece reaktif elektrofilik maddelerin ataklarından koruyan GST enzimleri aracılığıyla

gerçekleşen glutatyonun konjugasyon reaksiyonlarıdır. GST enzimi toksik ekzojen bileşikleri metabolize

edebildiğinden dolayı ayrıntılı biçimde memelilerde araştırılmıştır. Bu çalışmada GST enzimi insan eritrositlerinde

5.56 EU mg-1 protein spesifik aktiviteyle ve 65 %verimle 2316.0 kat saflaştırıldı. Saflaştırılan enzimin saflığını

kontrol etmek için SDS-poliakrilamid jel elektroforezi yapıldı ve molekül kütlesi yaklaşık 26 kDa olarak belirlendi.

Saflaştırılan GST enzimi üzerine inhibisyon etkisi gösteren amoksisilin ve vankomisin hidroklorür için IC50

değerleri ve Ki sabitleri hesaplanarak inhibisyon tipleri belirlendi. İnhibisyon çalışmalarının sonucu olarak, bu

antibiyotiklerin düşük dozlarda GST enzimini inhibe ettiği gözlendi.

Anahtar Kelimeler

Amoksisilin, vankomisin hidroklorür, glutatyon s- transferaz

Kaynakça

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