A Study of the Protective Properties of an Antibody-Based Antidote Metabolizing Organophosphorus Pesticide Paraoxon


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Abstract

A catalytic antibody A17 and its mutants highly efficiently interact with organophosphorus pesticide paraoxon. In this work, we studied the protective properties of antibody A17-K47 in paraoxon poisoning using a mouse model. The optimal paraoxon dose simulating the acute toxic effect of organophosphorus compounds was 550 μg/kg. The pharmacokinetic parameters of A17-K47 antibody were t1/2distr=7.2±1.4 min, t1/2el=330±20 min. The antibody did not cause toxic effects when administered at a ten-fold calculated therapeutic dose (610 mg/kg). The drug did not reduce mortality from acute paraoxon poisoning; however, the absence of drug toxicity opens up prospects for its use in symptomatic treatment of chronic paraoxon poisoning.

About the authors

Yu. A. Mokrushina

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Author for correspondence.
Email: yuliana256@mail.ru
Russian Federation, Moscow

A. V. Stepanova

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow

V. A. Palikov

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow region, Pushchino

A. V. Stepanov

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow

G. I. Belous

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow region, Pushchino

I. A. Dyachenko

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow region, Pushchino

V. D. Knorre

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow

I. V. Smirnov

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow

A. G. Gabibov

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yuliana256@mail.ru
Russian Federation, Moscow


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