Inhibitory Effect of Methotrexate (MTX) Used in Human Cancer Treatment on Paraoxonase-1 (PON1)

Söy&u, Hakan; Uluta&#;, Yakup; Köksa, Ekrem

doi:10.3923/ijp.2022.942.946

International J. of Pharmacology

2022

DOI: 10.3923/ijp.2022.942.946

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Inhibitory Effect of Methotrexate (MTX) Used in Human Cancer Treatment on Paraoxonase-1 (PON1)

Hakan Söy&u¹,

Yakup Uluta&#;²,

Ekrem Köksa³

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2023

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Cited by 1 publication

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Inhibition Effects of Oncological Drugs for Treatment of Cancer, on Paraoxonase-1 Enzyme (PON1) Activity and Cardiovascular Toxicity

Söyüt¹

2023

International J. of Pharmacology

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Background and Objective: Paraoxonase-1 Enzyme (PON1) is a high-density lipoprotein-associated cardioprotective enzyme that prevents the formation of oxidized low-density lipoprotein. This study focused on the investigation of the in vitro inhibition effects of trastuzumab and nivolumab, which are used in the treatment of cancer, on paraoxonase-1 enzyme activity. Materials and Methods: In this study, blood samples belonging to individuals aged 7-12 years were first taken and kept for the completion of coagulation. The serum was carefully separated by centrifugation. It was then used to investigate the inhibition effects of trastuzumab and nivolumab on the separated serum paraoxonase 1. In addition, the type of inhibition between enzymes and drugs was found by using Lineweaver-Burk curves. Results: Trastuzumab and nivolumab inhibited the human serum PON1 in vitro and their IC 50 and K i values were 0.0071 and 0.0062 µM, 0.0043 and 0.0053, respectively. Trastuzumab showed competitive inhibition. Nivolumab showed non-competitive inhibition. Conclusion: This study showed that trastuzumab and nivolumab inhibit PON1 enzymatic activity. These findings suggested that a decrease in the level of PON1 enzymatic activity may contribute to the increased risk of cardiovascular toxicity.

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Inhibition Effects of Oncological Drugs for Treatment of Cancer, on Paraoxonase-1 Enzyme (PON1) Activity and Cardiovascular Toxicity

Söyüt¹

2023

International J. of Pharmacology

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Inhibitory Effect of Methotrexate (MTX) Used in Human Cancer Treatment on Paraoxonase-1 (PON1)

Cited by 1 publication

References 18 publications

Inhibition Effects of Oncological Drugs for Treatment of Cancer, on Paraoxonase-1 Enzyme (PON1) Activity and Cardiovascular Toxicity

Inhibition Effects of Oncological Drugs for Treatment of Cancer, on Paraoxonase-1 Enzyme (PON1) Activity and Cardiovascular Toxicity

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