RJX Improves Wound Healing in Diabetic Rats

Abstract

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.

3D printable, injectable amyloid-based composite hydrogel of bovine serum albumin and aloe vera for rapid diabetic wound healing

“…Although process of epithelialization was complete in the A6B8-treated group, fibroblast and collagen regeneration were also more evident in the A6B8-treated group, with properly arranged bundles sited parallel to the newly formed epidermis in comparison with the A0B8- and A8B0-treated groups. 77…”

Transplanted artificial amnion membrane enhanced wound healing in third-degree burn injury diabetic mouse model

“…In general, during the wound healing process, re-epithelialization begins after the formation of granulation tissue at the wound site [ 31 ]. However, because wound healing mechanism is inhibited in diabetic mice, re-epithelialization in diabetic mice is prolonged compared with that in normal mice [ 32 ]. In our study, α-SMA-positive cells (myofibroblasts) were identified after POD 9 in granulation tissue of the artificial-AM group.…”

Mango ginger (Curcuma amada Roxb.) may alleviate the effect of high‐fat diet/streptozotocin‐induced diabetes by activation of the GSK‐3β/Fyn/Nrf2 pathway

“…The combination of HFD and low‐dose STZ is widely used to establish the type 2 diabetes model in rats (Sahin et al, 2019 ; Uckun et al, 2022 ; Wickramasinghe et al, 2022 ). Excessive fat intake elevated serum and liver FFA may promote inflammatory hepatic damage and insulin resistance (Ma et al, 2018 ), leading to the deterioration of glucose metabolism and subsequent hyperglycemia, hyperinsulinemia, and dyslipidemia (Sahin et al, 2019 ).…”

“…The homeostasis model assessment of insulin resistance (HOMA‐IR) was detected, as stated by Uckun et al ( 2022 ). The average fasting blood glucose levels (4.38 mmol/L) and insulin (10.63 mIU/L) were detected, and the coefficient was computed as 46.52.…”