Aminated β‐1,3‐D‐glucan has a dose‐dependent effect on wound healing in diabetic db/db mice

Abstract

Inflammatory responses are common in diabetes and are operative in angiopathy, neuropathy, and wound healing. There are indications of incomplete macrophage activation in diabetes and reduced expression of growth factors. We have previously found that up to 15 topical applications of the macrophage-stimulant, aminated β-1,3-D-glucan (AG), improved wound healing in db/db mice. The present open-label study was undertaken to examine dose-dependent effects of AG over 40 days in db/db mice. AG was given as a single dose (group 1), one dose every 10th day (group 2), five initial doses on consecutive days (group 3), and ≥15 doses (group 4). Controls were db/db mice receiving platelet-derived growth factor + insulin-like growth factor-1 (group 5), topical placebo (NaCl 9 mg/mL) and insulin (group 6), placebo (group 7), and a nondiabetic group receiving placebo (group 8). Seven to 14 animals were allocated to each group. Percentage wound closure 17 days after surgery in groups 1 and 2 were (mean ± standard error of the mean) 25.5 ± 5.3 and 32.2 ± 6.3, respectively. Corresponding closure in groups 3, 4, and 5 was 55.7 ± 5.0, 57.3 ± 5.0, and 55.6 ± 4.8, respectively (p < 0.05 vs. groups 1 and 2). Groups 6, 7, and 8 closed 32.0 ± 4.5, 38.2 ± 5.3, and 98.5 ± 0.4%, respectively. Significant association between the number of AG-dosages and wound closure indicates dose-related effects in db/db mice.

No Association between Glycemia and Wound Healing in an Experimental db/db Mouse Model

“…One hundred and ten of these received topical placebo wound treatment with 100  μ L of NaCl 9 mg/mL daily applied for five consecutive days (0–4). The remaining 39 animals had topical treatment with 100  μ L of the macrophage stimulant, aminated β -1,3-D-glucan (AG) at day 0 only [7]. We chose to include this group since this intervention was similar to topical placebo wound treatment regarding wound closure at day 13 and baseline characteristics (age, body weight, fPG, and p-lactate; all P > 0.1, t -tests) [7].…”

“…The remaining 39 animals had topical treatment with 100  μ L of the macrophage stimulant, aminated β -1,3-D-glucan (AG) at day 0 only [7]. We chose to include this group since this intervention was similar to topical placebo wound treatment regarding wound closure at day 13 and baseline characteristics (age, body weight, fPG, and p-lactate; all P > 0.1, t -tests) [7]. Furthermore, this group was similar regarding changes in weight (between days 7 and 13), fasting plasma glucose, and plasma lactate (both of the latter between day 0 and end of experiment; all P > 0.1, t -tests).…”

“…All experiments were performed within a time frame of 24 months. Results from 20  db/db mice have previously been presented [5, 7]. …”

Effect of the Modifications on the Physicochemical and Biological Properties of β-Glucan—A Critical Review

“…Some natural polysaccharide glycosaminoglycan activity during wound healing has been demonstrated. Dose-related (1→3)-β-glucan is a potential natural biological response modifier for wound healing and could enhance ulcer healing and increase epithelial hyperplasia, as well as increased inflammatory cell activity, angiogenesis, and fibroblast proliferation [111][112][113]. Water-soluble yeast β-1,3-glucan has excellent radical scavenging effects and can participate in the body's natural defense mechanisms and accelerate the process of skin wound healing.…”

Effects of AGE Inhibition with Aminoguanidine in a Diabetic &lt;i&gt;db/db&lt;/i&gt; Mouse Wound Model

“…Our previous studies on wound healing gave identical placebo results with or without topical applications of NaCl 9 mg/mL [23]. We therefore chose not to give additional topical placebo wound treatment in the groups with systemic AGu supply (groups 1 -3).…”