RJX Improves Wound Healing in Diabetic Rats
BackgroundWe 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....
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.874291/full |
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| author | Fatih M. Uckun Fatih M. Uckun Cemal Orhan Mehmet Tuzcu Ali Said Durmus Ibrahim H. Ozercan Michael Volk Kazim Sahin |
| author_facet | Fatih M. Uckun Fatih M. Uckun Cemal Orhan Mehmet Tuzcu Ali Said Durmus Ibrahim H. Ozercan Michael Volk Kazim Sahin |
| author_sort | Fatih M. Uckun |
| collection | DOAJ |
| description | BackgroundWe 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.MethodsIn 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.FindingsNotably, 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. |
| first_indexed | 2024-04-13T17:59:10Z |
| format | Article |
| id | doaj.art-d5d71df53e5645eda6a2339ec55cb731 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T17:59:10Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-d5d71df53e5645eda6a2339ec55cb7312022-12-22T02:36:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.874291874291RJX Improves Wound Healing in Diabetic RatsFatih M. Uckun0Fatih M. Uckun1Cemal Orhan2Mehmet Tuzcu3Ali Said Durmus4Ibrahim H. Ozercan5Michael Volk6Kazim Sahin7Drug Discovery Program, Reven Pharmaceuticals, Westminster, CO, United StatesDepartment of Developmental Therapeutics, Immunology, and Integrative Medicine, Ares Pharmaceuticals, St. Paul, MN, United StatesDepartment of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, TurkeyDepartment of Biology, Faculty of Science, Firat University, Elazig, TurkeyDepartment of Surgery Faculty of Veterinary Medicine, Firat University, Elazig, TurkeyDepartment of Pathology Faculty of Medicine, Firat University, Elazig, TurkeyDrug Discovery Program, Reven Pharmaceuticals, Westminster, CO, United StatesDepartment of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, TurkeyBackgroundWe 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.MethodsIn 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.FindingsNotably, 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.874291/fullCOVID-19RJXpharmacologypharmacodynamicsvitaminsnutrients |
| spellingShingle | Fatih M. Uckun Fatih M. Uckun Cemal Orhan Mehmet Tuzcu Ali Said Durmus Ibrahim H. Ozercan Michael Volk Kazim Sahin RJX Improves Wound Healing in Diabetic Rats Frontiers in Endocrinology COVID-19 RJX pharmacology pharmacodynamics vitamins nutrients |
| 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 | COVID-19 RJX pharmacology pharmacodynamics vitamins nutrients |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.874291/full |
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