Bazı Kemoterapötik İlaçların İnsan Serumu Paraoksonaz-1 (PON1) Üzerindeki İnhibisyon Etkisinin Araştırılması

Kemoterapötik tedavide sıklıkla kullanılan iki ilacın (kladribin ve mitoksantron) insan serum paraoksanaz1 (PON1) enzim aktivitesi üzerindeki etkilerini in vitro inceledik. Kemoterapötik kullanılan bu ilaçlar in vitro PON1 aktivitesini azalttı. Kladribin ve mitoksantron inhibisyon mekanizması yarışmasızdır. Kladribin ve mitoksantron için IC50 değerleri sırasıyla 0.077 mM, ve 0.099 mM, olarak hesaplandı ve Ki sabitleri sırasıyla 0.057 ± 0.016 mM ve 0.067 ± 0.027 mM,olarak hesaplandı. IC50 ve Ki değerleri, kladribin’in daha güçlü inhibisyona sahip olduğunu gösterdi. Bulduğumuz sonuçlar kemoterapötik tedavide sıklıkla kullanılan bu ilaçların düşük dozlarda aynı inhibisyon mekanizmaları ile enzim aktivitesini inhibe ettiğini göstermiştir.

Anahtar Kelimeler:

Paraoksonaz, inhibisyon, kladribin, mitoksantron

Investigation of Inhibition Effect of Some Chemotherapeutic Drugs on Human Serum Paraoxonase-1 (PON1)

We examined the effects of two different drugs (cladribine and mitoxantrone), which are frequently used in chemotherapeutic treatment, on human serum paraoxanase1 (PON1) enzyme activity in vitro. Chemotherapeutic drugs decreased in vitro PON1 activity. Cladribine and mitoxantrone inhibition mechanism were not competitive inhibitors. IC50 values for cladribine and mitoxantrone were calculated as 0.077 mM and 0.099 mM, respectively, and Ki constants were calculated as 0.057 ± 0.016 mM and 0.067 ± 0.027 mM, respectively. IC50 and Ki values showed that cladribine has a stronger inhibition. The results we found showed that these drugs, which are frequently used in chemotherapeutic treatment, inhibit enzyme activity with the same inhibition mechanisms at low doses.

Keywords:

Paraoxonase, inhibition, cladribine, mitoxantrone,

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