DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion
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
Affiliations
Elena A. Tukhovskaya
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
Elvira R. Shaykhutdinova
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
Alina M. Ismailova
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
Gulsara A. Slashcheva
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
Igor A. Prudchenko
Laboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, Russia
Inessa I. Mikhaleva
Laboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, Russia
Oksana N. Khokhlova
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
Arkady N. Murashev
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
Vadim T. Ivanov
Laboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, Russia
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.
