Pharmacokinetics of HLDF-6-AA Peptide in the Organism of Experimental Animals

Zolotarev, Yu. A.; Dadayan, A. K.; Kozik, V. S.; Shram, S. I.; Азев, В. Н.; Bogachouk, A. P.; Липкин, В. М.; Myasoedov, N. F.

doi:10.1134/s1068162019050145

Cited by 2 publications

(3 citation statements)

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“…The effect of the AF of HLDF-6 peptide on the parameters of binding between radiolabeled ligands and NMDA receptors on hippocampal membranes and between GABA-A and 5HT2A serotonin receptors on the membranes of the prefrontal cortex in BALB/c mice was investigated. Subchronic injection of the peptide into the murine hippocampus was shown to increase the amount of the ligand (G-3H MK-801) that bound [ 11 ] only for the NMDA glutamate receptors, an indication of the density of the corresponding receptors. Hence, the AF of HLDF-6 peptide restores the amount of NMDA receptors to its normal level, thus improving cognitive behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of the pharmacokinetics of HLDF-6 peptide has demonstrated that the peptide is extremely unstable in an animal organism: its half-life in rat plasma is 2 min. HLDF-6 is hydrolyzed starting at its C-end; dicarboxypeptidases make a major contribution to it [ 11 ]. Amidation of the C-terminal carboxylic group was used to protect the peptide against dicarboxypeptidases.…”

Section: Introductionmentioning

confidence: 99%

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Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer’s Disease

et al. 2017

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The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH2) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer’s disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 μg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze. The results testify to the fact that the pharmaceutical substance (PhS) based on the AF of HLDF-6 peptide at a dose of 250 μg/kg administered intranasally efficiently restores the disturbed cognitive functions in transgenic mice. These results are fully consistent with the data obtained in animal models of Alzheimer’s disease induced by the injection of the beta-amyloid (βA) fragment 25-35 into the giant-cell nucleus basalis of Meynert or by co-injection of the βA fragment 25-35 and ibotenic acid into the hippocampus, and the model of ischemia stroke (chronic bilateral occlusion of carotids, 2VO). According to the overall results, PhS based on AF HLDF-6 was chosen as an object for further investigation; the dose of 250 μg/kg was used as an effective therapeutic dose. Intranasal administration was the route for delivery.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer’s Disease

et al. 2017

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“…Part one" [12,13]. Experiments on animals were carried out following the rules adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes 6 [14,15]. The studies were performed according to an approved written protocol and in accordance with the Investigator's Standard Operating Procedures (SOP).…”

Section: Methodsmentioning

confidence: 99%