Bazı antibiyotiklerin Tip 2 diabetes mellitus’lu hastaların polimorfonüklear lökosit (PNL) fonksiyonları ve PNL’lerin miyeloperoksidaz aktivitesi, glutatyon ile malondialdehit düzeyleri üzerine in vitro etkisi

Amaç: Çalışmamızda diabetes mellitus (DM)’lu hastaların polimorf nüveli lökosit (PNL) fonksiyonları ile sağlıklı gönüllülerin miyeloperoksidaz (MPO) aktivitesi, glutatyon (GSH) ve malondialdehit (MDA) düzeylerini karşılaştırıp arasındaki ilişkiyi saptamayı amaçladık. Bunun yanında siprofloksasin, rifampisin ve doksisiklinin PNL fonksiyonları, MPO aktivitesi ve GSH ile MDA düzeyleri üzerine immunomodülatör etkilerini araştırdık.Yöntemler: Çalışmamızda Tip 2 diyabeti olan 13 hasta ve 13 sağlıklı gönüllü yer almaktadır. Antibiyotiklerin PNL fonksiyonları üzerine olan etkileri in vitro koşullarda araştırıldı. PNL’ler (1x107 hücre/ml) venöz kandan Ficoll-hypaque gradient santrifügasyon metodu kullanılarak izole edildi. PNL’lerin MPO aktivitesi modifiye O-dianisidin yöntemi, GSH miktarı Ellman yöntemi ve MDA düzeyleri ise Beuge yöntemi kullanılarak belirlendi.Bulgular: DM’lu hasta PNL’lerinin fagositik (p<0.05) ve hücre içi öldürme aktivitesi (p<0.01) sağlıklı gönüllülere göre anlamlı olarak azaldı. Siprofloksasin sağlıklı gönüllü ve tüm hasta PNL’lerinin fagositik ve hücre içi öldürme aktivitesini kontrol değerlere göre anlamlı olarak artırdı (p<0.01 ve p<0.01). Rifampisin, DM’lu hasta PNL’lerinin hücre içi öldürme aktivitesini anlamlı olarak artırdı (p<0.05). Rifampisin ve doksisiklin ise, sağlıklı gönüllü PNL’lerinin fagositik ve hücre içi öldürme aktivitesini kontrol değerlerine göre anlamlı olarak azalttı (p<0.05). Siprofloksasin (2.5 µg/ml) sağlıklı gönüllülerin (p<0.01) ve hastaların MPO aktivitesini ve MDA düzeyini ilaçsız kontrole göre anlamlı olarak artırdı (p<0.01). Ancak aynı ilaç DM’lu hasta PNL’lerinin GSH düzeyini anlamlı olarak azalttı (p<0.05).Sonuçlar: İmmün sistemi bozulmuş Tip 2 DM’lu hastalardaki ve sağlıklı gönüllerdeki MPO aktivitesi ile PNL fonksiyonları arasındaki ilişkinin önemi siprofloksasin ile hücresel immün sistemin desteklenmesi ve PNL’lerin MPO aktivitesi ile beraber PNL aktivitelerinin artışı ile gösterildi.

The effect of some antibiotics on polymorphonuclear leukocyte (PMN) functions and PMN’s myeloperoxidase activity, glutathione and malondialdehyde levels of patients with type 2 diabetes mellitus in vitro

Objective: In this study, our objective was to compare PMN functions and myeloperoxidase (MPO) activity, glutathione (GSH) and malondialdehyde (MDA) levels and assess the relationship between PMN functions and enzyme levels in patients with type 2 diabetes mellitus (T2DM) and healthy volunteers. We also examined the immunomodulatory effects of ciprofloxacin, rifampicine and doxycycline on PMN functions, MPO activity and GSH and MDA levels.Methods: Thirteen patients with T2DM and 13 healthy volunteers were included in the study. The effect of antibiotics on PMN functions were investigated in vitro. PMN’s (1x107cells/ml) were isolated from venous blood by Ficoll-hypaque gradient centrifugation method. MPO activity was assayed by modified O-dianisidine method. GSH level was determined using Ellman’s method and MDA level by Beuge’s method.Results: The PMN’s phagocytic (p<0.05) and intracellular killing activity (p<0.01) of T2DM patients significantly decreased when compared with healthy volunteers. Ciprofloxacin increased PMN’s phagocytic (p<0.01) and intracellular killing activity (p<0.01) of T2DM patients and healthy volunteers when compared with drug-free controls. Rifampicine increased PMN’s intracellular killing activity of patients with T2DM (p<0.05). Rifampicine and doxycycline decreased PMN’s phagocytic and inracellular activity of healthy volunteers (p<0.05). Ciprofloxacin increased PMN’s MPO activity (p<0.01) and MDA levels of T2DM patients (p<0.01) and healthy volunteers (p<0.01). However, it decreased PMN’s GSH levels of T2DM patients (p<0.05). Conclusions: The importance of the relationship between MPO activity and PMN functions was shown by the support of cellular immunity and increase of PMN’s MPO activity and PMN functions with ciprofloxacin in healthy volunteers and T2DM patients whose immune system is deteriorated.

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