Intravenous administration of heterodimeric phospholipase A2 HDP-1 disturbs cardiovascular system functions and biochemical composition of blood in anesthesiated rats

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Abstract

Heterodimeric phospholipase A2 HDP-1 from the venom of Nikolsky viper consists of two non-covalently bound subunits – HDP-1P and HDP-1In, the first of which exhibits lipolytic activity, while the second does not. The subunits have close molecular masses and similar amino acid sequences. Administration of HDP-1 and HDP-1P to anesthetized rats is accompanied by prolonged hypotensive effects, the intensity of which depends on the dose. With the administration of HDP-1P, the effect develops more slowly than in the case of HDP-1 containing both subunits, while individual HDP-1In does not affect hemodynamic parameters. It was found using electrocardiography that HDP-1 and HDP-1P affect the functioning of the rat heart, causing arrhythmia, which may indicate their ability to affect the innervation of the heart. The administration of HDP-1 and its subunits also leads to changes in biochemical blood parameters, indicating their damaging effect on cells and internal organs.

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About the authors

A. M. Ismailova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: utkin@ibch.ru

Branch

Russian Federation, Moscow; Pushcino

M. S. Severyukhina

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; the Federal State Budgetary Educational Institution of Higher Education “Russian Biotechnological University (ROSBIOTECH)”

Email: utkin@ibch.ru

Branch, Pushchino branch

Russian Federation, Moscow; Pushchino; Puschino

E. R. Shaykhutdinova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: utkin@ibch.ru

Branch

Russian Federation, Moscow; Pushcino

N. A. Perepechenova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: utkin@ibch.ru

Branch

Russian Federation, Pushchino

V. G. Starkov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: utkin@ibch.ru
Russian Federation, Moscow

I. A. Dyachenko

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; the Federal State Budgetary Educational Institution of Higher Education “Russian Biotechnological University (ROSBIOTECH)”

Email: utkin@ibch.ru

Branch, Pushchino branch

Russian Federation, Moscow; Pushchino; Pushchino

V. I. Tsetlin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: utkin@ibch.ru

Corresponding Member of the RAS

Russian Federation, Moscow

Yu. N. Utkin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Author for correspondence.
Email: utkin@ibch.ru
Russian Federation, Moscow

References

  1. Филькин C.Ю., Липкин А.В., Федоров А.Н. Суперсемейство фосфолипаз: структура, функции и применение в биотехнологии // Успехи биологической химии. 2020. Т. 60. С. 369–410.
  2. Dennis E.A., Cao J., Hsu Y.-H., et al. Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention // Chemical Reviews. 2011. V. 111. №10. P. 6130–6185.
  3. Schiavo G., Matteoli M., Montecucco C. Neurotoxins affecting neuroexocytosis // Pysiol. Rev. 2000. V. 80. P. 717–766.
  4. Chaisakul J., Isbister G.K., Tare M., et al. Hypotensive and vascular relaxant effects of phospholipase A2 toxins from Papuan taipan (Oxyuranus scutellatus) venom // Eur. J. Pharmacol. 2014. V. 723. P. 227–233.
  5. Silveira L.B., Marchi-Salvador D.P., Santos-Filho N.A., et al. Isolation and expression of a hypotensive and anti-platelet acidic phospholipase A2 from Bothrops moojeni snake venom // J. Pharm. Biomed. Anal. 2013. V. 73. P. 35–43.
  6. Ramazanova A.S., Zavada L.L., Starkov V.G., et al. Heterodimeric neurotoxic phospholipases A2-the first proteins from venom of recently established species Vipera nikolskii: implication of venom composition in viper systematics // Toxicon. 2008. Vol. 5. №4. P. 524–537.
  7. Animal Clinical Chemistry: A Practical Handbook for Toxicologists and Biomedical Researchers, Second Edition / Edited By G.O. Evans. Published April 8, 2009 by CRC Press. 366 р.
  8. Averin A., Starkov V., Tsetlin V., et al. Effects of the Heterodimeric Neurotoxic Phospholipase A2 from the Venom of Vipera nikolskii on the Contractility of Rat Papillary Muscles and Thoracic Aortas // Toxins (Basel). 2024. V. 16. №2. P. 100.
  9. Cicala C., Cirino G. Phospholipase A2-induced hypotension in the rat and its pharmacological modulation // Gen. Pharmacol. 1993. Vol. 24. №5. P. 1197–1202.
  10. Peterfi O., Boda F., Szabo Z., et al. Hypotensive Snake Venom Components-A Mini-Review // Molecules. 2019. Vol. 24. №15. P. 2778.
  11. Frangieh J., Rima M., Fajloun Z., et al. Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases // Molecules. 2021. Vol. 26. №8. P. 2223.
  12. Sartim M.A., Nogueira R.C., Cavalcante T.T.A., et al. Hemodynamic impairment induced by Crotoxin using in vivo and ex vivo approach in a rat model // Int. J. Biol. Macromol. 2023. V. 232. P. 123408.
  13. Akine A., Suzuka H., Hayashida Y., et al. Effects of ketamine and propofol on autonomic cardiovascular function in chronically instrumented rats // Auton. Neurosci. 2001. V. 87. №2-3. P. 201–208.

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2. Fig. 1. Changes in hemodynamic parameters after administration of HDP-1 (A, D), HDP-1P (B, E), and HDP-1In (C, E). * p ≤ 0.05 by Wilcoxon test for HDP-1 group at a dose of 250 μg/kg compared with baseline values ​​of the group; # p ≤ 0.05 by Wilcoxon test for HDP-1 groups at a dose of 400 μg/kg compared with baseline values ​​of the group; & p ≤ 0.05 by Wilcoxon test for HDP-1P groups at a dose of 250 μg/kg compared with baseline values ​​of the group.

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3. Fig. 2. Effect of HDP-1 and its subunits on the ECG of anesthetized rats. (A) standard ECG of the control group; (B) a single extrasystole upon administration of HDP-1 at a dose of 250 μg/kg; (C) cardiac arrest and bradycardia upon administration of HDP-1P at a dose of 250 μg/kg; (D) cardiac arrest manifested by an increase in the intervals between contractions upon administration of HDP-1P at a dose of 250 μg/kg.

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