Acidified Nitrite Accelerates Wound Healing in Type 2 Diabetic Male Rats: A Histological and Stereological Evaluation

Abstract

Impaired skin nitric oxide production contributes to delayed wound healing in type 2 diabetes (T2D). This study aims to determine improved wound healing mechanisms by acidified nitrite (AN) in rats with T2D. Wistar rats were assigned to four subgroups: Untreated control, AN-treated control, untreated diabetes, and AN-treated diabetes. AN was applied daily from day 3 to day 28 after wounding. On days 3, 7, 14, 21, and 28, the wound levels of vascular endothelial growth factor (VEGF) were measured, and histological and stereological evaluations were performed. AN in diabetic rats increased the numerical density of basal cells (1070 ± 15.2 vs. 936.6 ± 37.5/mm3) and epidermal thickness (58.5 ± 3.5 vs. 44.3 ± 3.4 μm) (all p < 0.05); The dermis total volume and numerical density of fibroblasts at days 14, 21, and 28 were also higher (all p < 0.05). The VEGF levels were increased in the treated diabetic wounds at days 7 and 14, as was the total volume of fibrous tissue and hydroxyproline content at days 14 and 21 (all p < 0.05). AN improved diabetic wound healing by accelerating the dermis reconstruction, neovascularization, and collagen deposition.

Topical spray of Wharton's jelly mesenchymal stem cells derived from umbilical cord accelerates diabetic wound healing

“…Formalin‐fixed samples were placed in baskets along with the number belonging to each rat. Then, routine steps, including dewatering in ascending alcohol percentages, clarification in xylenol and molding in paraffin were performed 19 . Then, 6‐micron thick sections were prepared from the tissues.…”

“…Second, we did not measure epidermal and dermal thickness, density, and elasticity in healthy rats (unwounded) in this study. Finally, contraction of the panniculus carnosus muscle in rats contributes to the wound healing process; this muscle does not exist in humans 19 . Wound repair in human is mainly driven by granulation and re‐epithelialization.…”

“…Then, routine steps, including dewatering in ascending alcohol percentages, clarification in xylenol and molding in paraffin were performed. 19 Then, 6-micron thick sections were prepared from the tissues. Hematoxylin and eosin (H&E) staining, Masson's trichrome staining and elastic staining of the slides were performed according to the standards.…”

“…Finally, contraction of the panniculus carnosus muscle in rats contributes to the wound healing process; this muscle does not exist in humans. 19 Wound repair in human is mainly driven by granulation and re-epithelialization. Therefore, the extrapolation of this data to humans should be done with caution and more research is needed on a human model before effectiveness can be translated.…”

Therapeutic Role of Nitric Oxide in Diabetic Wound Healing: A Systematic Review

“…(Fig. 9) Acidified nitrile in type-2 diabetes used to accelerates wound healing by quick rehabilitation of dermis and the enhancement neovascularisation and advance for collagen deposition in wound tissue [33].…”