Effect of a new acetylaminohexanic acid derivative on wound healing and wound blood supply in mice with a mutation in the Agouti gene with inhibition of NOS isoform expression
Authors
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Alexey A. Khentov
Belgorod State National Research University
https://orcid.org/0009-0006-4315-0828
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Albina V. Miller
Belgorod State National Research University
https://orcid.org/0000-0003-0162-9196
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Leonid V. Pazhinsky
Belgorod State National Research University
https://orcid.org/0009-0001-0655-0420
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Anton A. Bolgov
Belgorod State National Research University
https://orcid.org/0000-0001-9708-8181
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Irina A. Tatarenkova
Kursk State Medical University
https://orcid.org/0000-0002-6477-1934
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Polina K. Sunyaykina
Kursk State Medical University
https://orcid.org/0009-0009-8310-9768
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Lyudmila M. Danilenko
Belgorod State National Research University
https://orcid.org/0000-0001-6101-8712
DOI:
https://doi.org/10.18413/rrpharmacology.12.1048Abstract
Introduction: Metabolic disorders, particularly diabetes mellitus, can lead to the formation of chronic wounds, slowing healing processes. A key factor impeding wound healing is the decreased production of endogenous nitric oxide (NO) due to a hyperglycemic microenvironment. Nitric oxide (NO) is a key signaling molecule produced by three different isoforms of nitric oxide synthase (NOS) – iNOS, eNOS, and nNOS – which regulate all phases of skin wound healing.
Materials and Methods: The effect of N-acetyl-6-aminohexanoic acid derivative in the form of a 5% carbopol-based hydrogel dosage form (carbopol 940) with 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate (LHT 2-18) on wound healing was studied during blockade of eNOS and iNOS nitric oxide synthase synthesis by intraperitoneal administration of a non-selective NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) at a dose of 25 mg/kg/day and aminoguanidine at a dose of 50 mg/kg/day, respectively. The studies were conducted on 30 Agouti viable yellow (Avy/a) mice weighing 42.9±0.12 g, which indicates the development of obesity. The degree of wound healing and wound blood flow were assessed on days 3, 7, 14, and 21. Wound healing was assessed using the gravimetric method. Expression levels of eNOS, iNOS, and VEGF mRNA were analyzed using quantitative PCR.
Results: Topical application of 5% hydrogel based on the LHT 2-18 complex improves the rate of wound healing in Avy/a mice when administered L-NAME and aminoguanidine and local blood flow indices, increases the level of mRNA expression of the eNOS and VEGF genes and reduces the level of iNOS.
Conclusion: The identified regenerative effect of the LHT 2-18 complex is of interest for further study with the aim of developing an effective agent that stimulates reparative regeneration of wounds, including those caused by metabolic damage.
Graphical Abstract
Keywords:
acetylaminohexanoic acid derivative, aminoguanidine, nitric oxide, N-nitro-L-arginine methyl ester (L-NAME)References
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Copyright (c) 2026 Khentov AA, Miller AV, Pazhinsky LV, Bolgov AA, Tatarenkova IA, Sunyaykina PK, Danilenko LM
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