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RJX Improves Wound Healing in Diabetic Rats

BACKGROUND: We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et a...

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Autores principales: Uckun, Fatih M., Orhan, Cemal, Tuzcu, Mehmet, Durmus, Ali Said, Ozercan, Ibrahim H., Volk, Michael, Sahin, Kazim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201994/
https://www.ncbi.nlm.nih.gov/pubmed/35721744
http://dx.doi.org/10.3389/fendo.2022.874291
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author Uckun, Fatih M.
Orhan, Cemal
Tuzcu, Mehmet
Durmus, Ali Said
Ozercan, Ibrahim H.
Volk, Michael
Sahin, Kazim
author_facet Uckun, Fatih M.
Orhan, Cemal
Tuzcu, Mehmet
Durmus, Ali Said
Ozercan, Ibrahim H.
Volk, Michael
Sahin, Kazim
author_sort Uckun, Fatih M.
collection PubMed
description BACKGROUND: We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats. METHODS: In the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks. FINDINGS: Notably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX – at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) – accelerates the healing of excision wounds as well burn injury in diabetic rats.
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spelling pubmed-92019942022-06-17 RJX Improves Wound Healing in Diabetic Rats Uckun, Fatih M. Orhan, Cemal Tuzcu, Mehmet Durmus, Ali Said Ozercan, Ibrahim H. Volk, Michael Sahin, Kazim Front Endocrinol (Lausanne) Endocrinology BACKGROUND: We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats. METHODS: In the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks. FINDINGS: Notably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX – at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) – accelerates the healing of excision wounds as well burn injury in diabetic rats. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201994/ /pubmed/35721744 http://dx.doi.org/10.3389/fendo.2022.874291 Text en Copyright © 2022 Uckun, Orhan, Tuzcu, Durmus, Ozercan, Volk and Sahin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Uckun, Fatih M.
Orhan, Cemal
Tuzcu, Mehmet
Durmus, Ali Said
Ozercan, Ibrahim H.
Volk, Michael
Sahin, Kazim
RJX Improves Wound Healing in Diabetic Rats
title RJX Improves Wound Healing in Diabetic Rats
title_full RJX Improves Wound Healing in Diabetic Rats
title_fullStr RJX Improves Wound Healing in Diabetic Rats
title_full_unstemmed RJX Improves Wound Healing in Diabetic Rats
title_short RJX Improves Wound Healing in Diabetic Rats
title_sort rjx improves wound healing in diabetic rats
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201994/
https://www.ncbi.nlm.nih.gov/pubmed/35721744
http://dx.doi.org/10.3389/fendo.2022.874291
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