Evaluation of the impacts of antibiotic drugs on PON 1; a major bioscavenger against cardiovascular diseases

Paroxonase 1(PON1) is an antiatherogenic enzyme which is also an organophosphate hydrolyzer. It has crucial roles in detoxification of highly toxic substances and protecting LDL against oxidation. Decrease in the levels of this enzyme is a great risk for the patients with cardiovascular diseases, diabetes mellitus, chronic renal failure, rheumatoid arthritis, hyperthyroidism, and age-related macular degeneration. Therefore, inhibitors and activators of PON1 must be well-characterized, and drug studies would be a good starting point in this regard. Moreover, purification of PON1 has been a challenge for scientists due to its tight association with HDL. Here we report the purification of human serum PON1 using very simple methods and investigation of the interactions between the enzyme and some commonly used antibiotics. We purified PON1 from human serum with a high specific activity and used the pure enzyme for inhibition studies. We observed that some antibiotics inhibit the enzyme at very low doses while some are efficient at higher doses. The antibiotics exhibited different inhibition mechanisms. We concluded that usage of these antibiotics would be very dangerous in some cases. (C) 2009 Elsevier B.V. All rights reserved.