Investigation of Inhibition of Busulfan (Chemotherapeutic Drug) on Human Serum Paraoxonase-1 (PON1)

Hakan Soyut

Background and Objective: Paraoxonase 1 (PON1) is an antiatherogenic lactonase. It plays the role of an antioxidant enzyme by protecting HDLs from oxidative stress and also has important roles such as protection of Low-Density Lipoprotein (LDL) against oxidation and detoxification of highly toxic substances. Lowering the levels of this enzyme is a major risk in patients with cardiovascular disease. This study, it was aimed to investigate the in vitro effect of busulfan which is widely used in chemotherapy, on the human paraoxonase-1 enzyme. Materials and Methods: This study identifies interactions between the enzyme and busulfan, which is widely used in cancer chemotherapy. Paraoxonase activity measurement was used to determine the chemotherapeutic drug constants. Results: This study found that busulfan exhibited very potent inhibitory properties for human serum PON1 with an IC₅₀ value of 77 μM and an average K_i value of 42.83 μM. Busulfan showed competitive inhibition. Conclusion: The use of busulfan, which has a very strong inhibition, in chemotherapeutic treatment can be very dangerous.

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