Ability of lactoferrin to inhibit oxidative/halogenative stress and improve wound healing in rats with experimental hyperglycemia

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Abstract

BACKGROUND: Leukocyte myeloperoxidase catalyzes the formation of HOCl, which, by oxidizing and chlorinating biomolecules, contributes to the development of oxidative/halogenative stress. The latter in hyperglycemia may interfere with wound healing in patients with diabetes mellitus complications.

AIM: Evaluation of the concentration of markers of oxidative/halogenative stress and NETosis in the blood of experimental rats with hyperglycemia, its correction with lactoferrin, as well as elucidation of the effect of this multifunctional protein on skin wound healing.

MATERIALS AND METHODS: For the experimental modeling of hyperglycemia, the animals were injected once with streptozotocin at a dosage of 43 mg/kg body weight. Blood samples were collected from the tail vein of anesthetized animals. Glucose was measured by the electrochemical method. Markers of oxidative/halogenative stress were detected by the immunoenzymatic and spectrophotometric methods.

RESULTS: It was shown that in rats with streptozotocin-induced hyperglycemia, a “prophylactic+therapeutic” supplementation of lactoferrin (at a dose of 250 mg/kg on days 5, 3, and 1 before and days 2, 4, 6, and 8 after streptozotocin injection) significantly decreased blood concentration of glucose (fasting), myeloperoxidase, chlorinated ceruloplasmin, complexes of myeloperoxidase/DNA, and also prevented the decrease in thiols (SH-groups) and the activity of erythrocyte glutathione peroxidase. Moreover, lactoferrin administered according to the above regimen to rats with experimental hyperglycemia promoted wound healing, which was manifested by a 28% decrease in the wound area compared to the control animals.

CONCLUSIONS: The results obtained indicate that lactoferrin has an ability in a hyperglycemia model in animals to reduce not only the hyperglycemia level, but also to prevent the development of oxidative/halogenative stress and NETosis, which leads to improved wound healing.

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About the authors

Alexey V. Sokolov

Institute of Experimental Medicine; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency

Email: biochemsokolov@gmail.com
ORCID iD: 0000-0001-9033-0537
SPIN-code: 7427-7395

Dr. Sci. (Biology), Head of the Laboratory of Biochemical Genetics of the Department of Molecular Genetics; Senior Research Associate of Laboratories of Physical and Chemical Research and Analysis Methods

Russian Federation, Saint Petersburg; 1a Malaya Pirogovskaya St., Moscow, 119435

Viktor A. Ivanov

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency

Email: Vanov.va@inbox.ru
ORCID iD: 0000-0003-4766-1386
SPIN-code: 7531-5950

Junior Research Associate of Laboratories of Physical and Chemical Research and Analysis Methods

Russian Federation, 1a Malaya Pirogovskaya St., Moscow, 119435

Valeria A. Kostevich

Institute of Experimental Medicine; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency

Email: hfa-2005@yandex.ru
ORCID iD: 0000-0002-1405-1322
SPIN-code: 2726-2921

Cand. Sci. (Biology), Senior Research Associate of the Department of Molecular Genetics, Junior Research Associate of Laboratories of Physical and Chemical Research and Analysis Methods

Russian Federation, Saint Petersburg; 1a Malaya Pirogovskaya St., Moscow, 119435

Nikolay P. Gorbunov

Institute of Experimental Medicine

Email: niko_laygo@mail.ru
ORCID iD: 0000-0003-4636-0565
SPIN-code: 6289-7281

Postgraduate student, Research Associate of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Irina V. Voynova

Institute of Experimental Medicine

Email: iravoynova@mail.ru
ORCID iD: 0009-0006-3690-0192

Cand. Sci. (Biology), Research Associate of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Vadim B. Vasilyev

Institute of Experimental Medicine

Email: vadim@biokemis.ru
ORCID iD: 0000-0002-9707-262X
SPIN-code: 6699-6350

MD, Dr. Sci. (Medicine), Head of the Department of Molecular Genetics

Russian Federation, Saint Petersburg

Sergey A. Gusev

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency

Email: ser_gus@mail.ru
ORCID iD: 0000-0003-0383-2649

Dr. Sci. (Medicine), Chief Research Associate of Laboratories of Physical and Chemical Research and Analysis Methods

1a Malaya Pirogovskaya St., Moscow, 119435

Oleg M. Panasenko

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency

Author for correspondence.
Email: o-panas@mail.ru
ORCID iD: 0000-0001-5245-2285
SPIN-code: 3035-6808

Dr. Sci. (Biology), Professor, Corresponding Member of the RAS, Head of Department of Biophysics

Russian Federation, 1a Malaya Pirogovskaya St., Moscow, 119435

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2. Figure. Changes in fasting glucose concentration in venous blood of animals (rats) with experimental hyperglycemia under different lactoferrin regimens. Data are presented as median and quartiles [ Q 1 ; Q 3 ] . 1, Lactoferrin ( 250 mg/kg ) administration on days 5, 3, 1 days before and 2, 4, 6, 8 days after streptozotocin introduction. 2, Lactoferrin ( 250 mg/kg ) administration daily, starting 5 days before streptozotocin introduction. 3, Lactoferrin (50 mg/kg) administration daily on days 1 to 5 after streptozotocin introduction. Curves of the “K” family — control groups of animals, in which isotonic saline instead of lactoferrin was used in the same volume and regimen as for lactoferrin

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