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

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.