Key result
Trastuzumab and nivolumab inhibited human serum PON1 in vitro with IC50 values of 0.0071 and 0.0062 µM, respectively, suggesting a potential mechanism for cardiovascular toxicity.
Why the study?
PON1 is a cardioprotective enzyme that prevents ox-LDL formation, prompting investigation into the in vitro inhibition effects of trastuzumab and nivolumab on its activity.
Do trastuzumab and nivolumab inhibit paraoxonase-1 enzyme (PON1) activity in vitro?
Do trastuzumab and nivolumab inhibit paraoxonase-1 enzyme (PON1) activity in vitro?
Effect estimate: IC50 0.0071 and 0.0062 µM; Ki 0.0043 and 0.0053
Trastuzumab and nivolumab inhibit the cardioprotective enzyme PON1 in vitro, suggesting a potential mechanism for their cardiovascular toxicity.
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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Hakan Söyüt (2022) studied this question. Trastuzumab and nivolumab was evaluated on Inhibition of human serum PON1 in vitro (IC50 and Ki values) (IC50 0.0071 and 0.0062 µM; Ki 0.0043 and 0.0053). Trastuzumab and nivolumab inhibited human serum PON1 in vitro with IC50 values of 0.0071 and 0.0062 µM, respectively, suggesting a potential mechanism for cardiovascular toxicity.
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