DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion

A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in...

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Main Authors: Elena A. Tukhovskaya, Elvira R. Shaykhutdinova, Alina M. Ismailova, Gulsara A. Slashcheva, Igor A. Prudchenko, Inessa I. Mikhaleva, Oksana N. Khokhlova, Arkady N. Murashev, Vadim T. Ivanov
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/9/4/407
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author Elena A. Tukhovskaya
Elvira R. Shaykhutdinova
Alina M. Ismailova
Gulsara A. Slashcheva
Igor A. Prudchenko
Inessa I. Mikhaleva
Oksana N. Khokhlova
Arkady N. Murashev
Vadim T. Ivanov
author_facet Elena A. Tukhovskaya
Elvira R. Shaykhutdinova
Alina M. Ismailova
Gulsara A. Slashcheva
Igor A. Prudchenko
Inessa I. Mikhaleva
Oksana N. Khokhlova
Arkady N. Murashev
Vadim T. Ivanov
author_sort Elena A. Tukhovskaya
collection DOAJ
description A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.
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spelling doaj.art-885a2a8fb9224d2896bb5d7cf4f79a012023-11-21T14:56:23ZengMDPI AGBiomedicines2227-90592021-04-019440710.3390/biomedicines9040407DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during ReperfusionElena A. Tukhovskaya0Elvira R. Shaykhutdinova1Alina M. Ismailova2Gulsara A. Slashcheva3Igor A. Prudchenko4Inessa I. Mikhaleva5Oksana N. Khokhlova6Arkady N. Murashev7Vadim T. Ivanov8Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, RussiaBiological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, RussiaBiological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, RussiaBiological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, RussiaLaboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, RussiaLaboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, RussiaBiological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, RussiaBiological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, RussiaLaboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, RussiaA structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.https://www.mdpi.com/2227-9059/9/4/407Delta-Sleep-Inducing Peptide (DSIP)KND peptidemyocardial infarctionstroke
spellingShingle Elena A. Tukhovskaya
Elvira R. Shaykhutdinova
Alina M. Ismailova
Gulsara A. Slashcheva
Igor A. Prudchenko
Inessa I. Mikhaleva
Oksana N. Khokhlova
Arkady N. Murashev
Vadim T. Ivanov
DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
Biomedicines
Delta-Sleep-Inducing Peptide (DSIP)
KND peptide
myocardial infarction
stroke
title DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
title_full DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
title_fullStr DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
title_full_unstemmed DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
title_short DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
title_sort dsip like knd peptide reduces brain infarction in c57bl 6 and reduces myocardial infarction in sd rats when administered during reperfusion
topic Delta-Sleep-Inducing Peptide (DSIP)
KND peptide
myocardial infarction
stroke
url https://www.mdpi.com/2227-9059/9/4/407
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