PMID- 34721760 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20231108 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2021 DP - 2021 TI - Effect of Vitamin D3 in combination with Omega-3 Polyunsaturated Fatty Acids on NETosis in Type 2 Diabetes Mellitus Patients. PG - 8089696 LID - 10.1155/2021/8089696 [doi] LID - 8089696 AB - An understanding of the consequences of oxidative/halogenative stress triggered by neutrophil activation is impossible without considering NETosis. NETosis, formation of neutrophil extracellular traps (NETs), is known to promote microthrombus formation and impair wound healing in type 2 diabetes mellitus (T2DM) patients. Therefore, there is a need to search for drugs and treatment approaches that could prevent excessive NET formation. We aimed to evaluate the effect of vitamin D3 in combination with omega-3 polyunsaturated fatty acids (vitamin D3/omega-3 PUFAs) on NETosis in T2DM patients with purulent necrotizing lesions of the lower extremities. Patients and healthy subjects had vitamin D3 deficiency. Patients received, beyond standard treatment, 6000 IU of vitamin D3 and 480 mg of omega-3 PUFAs, and healthy subjects 1000 IU of vitamin D3 and 240 mg of omega-3 PUFAs daily for seven days. Neutrophil activation in ex vivo blood by phorbol-12-myristate-13-acetate (PMA) was used as a NETosis model. The percentage of blood NETs relative to leukocytes (NET(background)) before vitamin D3/omega-3 PUFA supplementation was 3.2%-4.9% in healthy subjects and 1.7%-10.8% in patients. These values rose, respectively, to 7.7%-9.1% and 4.0%-17.9% upon PMA-induced NETosis. In addition, the leukocyte count decreased by 700-1300 per 1 muL in healthy subjects and 700-4000 per 1 muL in patients. For both patients and healthy subjects, taking vitamin D3/omega-3 PUFAs had no effect on NET(background) but completely inhibited PMA-induced NET formation, though neutrophils exhibited morphological features of activation. Also, leukocyte loss was reduced (to 500 per 1 muL). For patients on standard treatment alone, changes occurred neither in background NETs and leukocytes nor in their amount after PMA stimulation. The decreased ability of neutrophils to generate NETs, which can be achieved by vitamin D3/omega-3 PUFA supplementation, could have a positive effect on wound healing in T2DM patients and reduce the incidence and severity of complications. CI - Copyright (c) 2021 Liliya Yu. Basyreva et al. FAU - Basyreva, Liliya Yu AU - Basyreva LY AUID- ORCID: 0000-0002-5170-9824 AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Vakhrusheva, Tatyana V AU - Vakhrusheva TV AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Letkeman, Zoya V AU - Letkeman ZV AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Maximov, Dmitry I AU - Maximov DI AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Fedorova, Evgeniya A AU - Fedorova EA AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Panasenko, capital O, Cyrillicleg M AU - Panasenko capital O, CyrillicM AUID- ORCID: 0000-0001-5245-2285 AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Ostrovsky, Evgeny M AU - Ostrovsky EM AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. FAU - Gusev, Sergey A AU - Gusev SA AD - Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia. LA - eng PT - Journal Article DEP - 20211022 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Fatty Acids, Omega-3) RN - 1C6V77QF41 (Cholecalciferol) RN - 25167-62-8 (Docosahexaenoic Acids) RN - AAN7QOV9EA (Eicosapentaenoic Acid) SB - IM MH - Aged MH - Aged, 80 and over MH - Case-Control Studies MH - Cells, Cultured MH - Cholecalciferol/adverse effects/*therapeutic use MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy MH - Docosahexaenoic Acids/therapeutic use MH - Drug Therapy, Combination MH - Eicosapentaenoic Acid/therapeutic use MH - Extracellular Traps/*drug effects/metabolism MH - Fatty Acids, Omega-3/adverse effects/*therapeutic use MH - Female MH - Humans MH - Leg Ulcer/blood/diagnosis/*drug therapy MH - Male MH - Middle Aged MH - Neutrophil Activation/*drug effects MH - Neutrophils/*drug effects/metabolism MH - Pilot Projects MH - Time Factors MH - Treatment Outcome MH - Vitamin D Deficiency/blood/diagnosis/*drug therapy MH - Wound Healing/drug effects PMC - PMC8556114 COIS- The authors declare no competing financial and nonfinancial interests. EDAT- 2021/11/02 06:00 MHDA- 2022/02/08 06:00 PMCR- 2021/10/22 CRDT- 2021/11/01 09:16 PHST- 2021/07/29 00:00 [received] PHST- 2021/09/07 00:00 [revised] PHST- 2021/09/27 00:00 [accepted] PHST- 2021/11/01 09:16 [entrez] PHST- 2021/11/02 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/10/22 00:00 [pmc-release] AID - 10.1155/2021/8089696 [doi] PST - epublish SO - Oxid Med Cell Longev. 2021 Oct 22;2021:8089696. doi: 10.1155/2021/8089696. eCollection 2021.