STRUCTURAL REACTIONS OF CD-1 MICE HEART AND LIVER TO A SINGLE INJECTION OF BOROCAPTATE SODIUM
Vladimir V. Kanygin,
Elena V. Koldysheva,
Evgeny L. Zav’yalov,
Ivan A. Razumov,
Ol'ga I. Solovyova,
Aleksandr I. Kichigin,
Ekaterina A. Butikova,
Valentina I. Kapustina https://doi.org/10.20340/mv-mn.2023.31(3).812
Abstract
Boron neutron capture therapy is considered a promising method for the treatment of malignant tumors of the head and neck. It is believed that to increase the effectiveness of this type of therapy, the use of large doses of boron is required, which may entail damaging effects on healthy tissue. One of the substances used in the clinical practice of boron neutron capture therapy is sodium boroncaptate Na2B12H11SH (BSH), enriched with the 10B boron isotope. The purpose of the study was to study the structural reactions of the myocardium and liver of CD-1 mice after administration of BSH. A light-optical and polarization-microscopic study of the myocardium and liver of male CD-1 mice (n=56) was carried out after injection of a boron-containing substance in doses of 100 and 1000 mg/kg, once, intraperitoneally. Assessment of structural changes in the myocardium and liver was carried out 1, 3 and 7 days after BSH administration. A single injection of BSH at a dose of 100 mg/kg did not lead to the death of animals, whereas 3 hours after the injection of BSH at a dose of 1000 mg/kg, 1 animal died. The body weight of the animals changed slightly during the experiment. Analysis of heart weight showed a decrease in this indicator on days 3 and 7 compared with indicators in the same groups on day 1 of the experiment. When analyzing the dynamics of changes in liver mass, no significant changes were revealed during the experiment. The main structural changes in the myocardium included lytic and contractural damage to cardiomyocytes, hemodynamic disturbances in the form of pronounced venous and capillary congestion. Liver damage was manifested in dystrophic changes in hepatocytes, the appearance after 3 days of monocellular necrosis of hepatocytes and pericentral mononuclear infiltrates. The data obtained indicate that the used doses of BSH 100 and 1000 mg/kg with a single injection cause structural changes in the myocardium and liver of varying severity, which persist for 7 days of observation.
About the Authors
Vladimir V. Kanygin
Budker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk National Research State University, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Candidate of Medical Sciences, Docent, Senior Researcher of the Budker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences; Head of the Laboratory of Nuclear and Innovative Medicine and Associate Professor of the Department of Elementary Particle Physics of the Novosibirsk National Research State University
Competing Interests:
The author declares that he did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Elena V. Koldysheva
Federal Research Center of the Fundamental and Translational Medicine, Novosibirsk National Research State University, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Doctor of Biological Sciences, Chief Researcher, Head of the Laboratory of Molecular Mechanisms of Pathological Processes of the Institute of Molecular Pathology and Pathomorphology of the Federal Research Center for Fundamental and Translational Medicine; Senior Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University
Competing Interests:
The author declares that she did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Evgeny L. Zav’yalov
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk National Research State University, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Candidate of Biological Sciences, Head of the SPF-Vivarium of the Center for Preclinical Trials of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University
Competing Interests:
The author declares that he did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Ivan A. Razumov
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk National Research State University, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Doctor of Biological Sciences, Senior Researcher of the Laboratory of Genetics of Laboratory Animals of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Senior Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University
Competing Interests:
The author declares that he did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Ol'ga I. Solovyova
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk National Research State University, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Master of Biology, Junior Researcher of the SPF-Vivariums of the Center for Preclinical Trials of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University
Competing Interests:
The author declares that she did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Aleksandr I. Kichigin
Budker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Candidate of Medical Sciences, Researcher
Competing Interests:
The author declares that he did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Ekaterina A. Butikova
Novosibirsk National Research State University, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Studentin
Competing Interests:
The author declares that she did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
Valentina I. Kapustina
Federal Research Center for Fundamental and Translational Medicine, Novosibirsk
Russian Federation
Competing Interests:
Russian Federation
Candidate of Biological Sciences, Senior Researcher of the Laboratory of Clinical Morphology of the Most Important Diseases of the Institute of Molecular and General Pathology
Competing Interests:
The author declares that she did no have conflicts of interest in the planning, implementation, financing and use of the results of this study
References
1. Hatanaka H. Boron-neutron capture therapy for tumors. Glioma. 1986;1-28. DOI:10.1007/978-3-642-84127-9_18
2. Wang S, Zhang Z, Miao L, Li Y. Boron Neutron Capture Therapy: Status and Challenges. Front Oncol. 2022;12:788770. DOI: 10.3389/fonc.2022.788770
3. Miyatake SI, Wanibuchi M, Hu N, Ono K. Boron neutron capture therapy for malignant brain tumors. J Neurooncol. 2020;149:1-11. DOI: 10.1007/s11060-020-03586-6
4. Farhood B, Samadian H, Ghorbani M, et al. Physical, dosimetric and clinical aspects and delivery systems in neutron capture therapy. Reports of Practical Oncology&Radiotherapy. 2018;23(5):462-473. DOI:10.1016/j.rpor.2018.07.002
5. Locher GL. Biological effects and therapeutic possibilities of neutrons. Am J Roentgenol Radium Ther. 1936;36:1-13
6. Barth RF, Mi P, Yang W. Boron delivery agents for neutron capture therapy of cancer. Cancer Commun (London). 2018;38(1):35. DOI:10.1186/s40880-018-0299-7
7. Fukuda H, Sauerwein W, Masutani M, Hopewell J. Response of Normal Tissues to Boron Neutron Capture Therapy (BNCT) with 10B-Borocaptate Sodium (BSH) and 10B-Paraboronophenylalanine (BPA). Cells. 2021;10(11):2883. DOI:10.3390/cells10112883
8. Suzuki M, Masunaga S, Kinashi Y, et al. Intra-arterial administration of sodium borocaptate bsh/lipiodol emulsion delivers B-10 to liver tumors highly selectively for boron neutron capture therapy: experimental studies in the rat liver model. Int J Radiation oncology biol Phys. 2004;59(1):260-266. DOI:10.1016/j.ijrobp.2003.12.018
9. Capala J, Stenstam BH, Sköld K, et al. Boron neutron capture therapy for glioblastoma multiforme: clinical studies in Sweden. J Neuro-Oncol. 2003;62:135-144. DOI:10.1007/BF02699940
10. Wittig A, Moss RLM, Sauerwein WAG. Glioblastoma, brain metastases and soft tissue sarcoma of extremities: Candidate tumors for BNCT. Ap-plied Radiation and Isotopes. 2014;88:46-49. DOI:10.1016/j.apradiso.2013.11.038
11. Bendel P, Wittig A, Basilico F, et al. Metabolism of bo-rono-phenylalanine-fructose complex (BPA-fr) and borocaptate sodium (BSH) in cancer patients--results from EORTC trial 11001. J Pharm Biomed Anal. 2010;51(1):284-287. DOI:10.1016/j.jpba.2009.08.018
12. Wittig A, Stecher-Rasmussen F, Hilger RA, et al. Sodium mercaptoundecahydro-closo-dodecaborate (BSH), a boron carrier that merits more atten-tion. Applied Radiation and Isotopes. 2011;69(12):1760-1764. DOI:10.1016/j.jpba.2009.08.018
13. Lushnikova EL, Klinnikova MG, Molodykh OP, Nepomnyashchikh LM. Morfologicheskie proyavleniya remodelirovaniya serdtsa pri dilyatatsion-noy kardiomiopatii antratsiklinovogo geneza. Byull Eksper Biol. 2004;138(12):684-689 In Russian
14. Larionova VB, Snegovoy AV. Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors. Onco-hematology. 2020;15(4):65-81. DOI:10.17650/1818-8346-2020-15-4-65-81
15. Tan W. Cardiotoxicity. Drug Induced Cardiotoxicity: Mechanism, Prevention and Management. 2018:7. DOI:10.5772/intechopen.79611
16. Lushnikova EL, Nepomnyashchikh LM, Tolstikova TG. Patomorfologiya myshechnykh kletok serdtsa pri deystvii tsiklofosfamida i triterpenoidov. Moskva: Izd-vo RAMN, 2009.- 272 s. In Russian
17. Lushnikova EL, Molodykh OP, Nikityuk DB, et al. Strukturny analiz miokarda pri eksperimental'noy antratsiklinovoy kardiomiopatii i adrenali-novykh vozdeystviyakh. Bull Expr Biol i Med. 2018;166(11):641-647. In Russian
18. Nepomnyashchikh LM, Molodykh OP, Lushnikova EL, Sorokina YuA. Morfogenez i gistostereologichesky analiz gepatopatii, indutsirovannoy tsiklofosfomidom. Bull Exp Biol i Med. 2010;149(1):113-119. In Russian
19. Vatutin NT, Sklyannaya EV, El'-Hatib MA i dr. Gepatotoksichnost' protivoopukholevykh preparatov: sovremennoe sostoyanie problemy. Ros-siysky szurnal oncologii. 2016;21(6):325-333. DOI:10.18821/1028-9984-2016-21-6-325-333 In Russian
20. Hung Y-H, Lin Y-C, Lin Y-T, et al. Therapeutic Efficacy and Radiobiological Effects of Boric Acid-mediated BNCT in a VX2 Multifocal Liver Tumor-bearing Rabbit Model. Anticancer research. 2019;39:5495-5504. DOI:10.21873/anticanres.13742
21.
Supplementary files
In a study on laboratory mice of the CD-1 line, with a single injection of used in the tumor clinic for boron neutron capture radiotherapy a radioactive boron isotope preparation in the form of 10B-Borocaptate sodium at doses of 100 and 1000 mg/kg were detected structural dystrophic changes in the myocardium and liver of varying expressiveness, persisting within 7 days
Review
For citations:
Kanygin V.V., Koldysheva E.V., Zav’yalov E.L., Razumov I.A., Solovyova O.I., Kichigin A.I., Butikova E.A., Kapustina V.I. STRUCTURAL REACTIONS OF CD-1 MICE HEART AND LIVER TO A SINGLE INJECTION OF BOROCAPTATE SODIUM. Morphological newsletter. 2023;31(3):30-37. (In Russ.) https://doi.org/10.20340/mv-mn.2023.31(3).812
Views:
372
