Pyridoxamine ameliorates methylglyoxal‐induced macrophage dysfunction to facilitate tissue repair in diabetic wounds

• DOI: 10.1111/iwj.13597
• Publication Date: 2021-04-01T01:30:24Z
• Authors: Minfei Jiang; Aobuliaximu Yakupu; Haonan Guan; Jiaoyun Dong; Yingkai Liu; Fei Song; Jiajun Tang; Ming Tian; Yiwen Niu; Shuliang Lu
• Keywords: Pyridoxamine

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher plasma concentration, lower extremity amputation rate. Here, we aimed identify mechanisms of MGO-induced dysfunction. We observed that accumulation MGO-derived AGEs in human diabetic wounds increased, whereas expression glyoxalase 1 (GLO1), key metabolic enzyme MGO, decreased. show for first time topical application pyridoxamine (PM), natural vitamin B6 analogue, reduced wound tissue type-2 mice, promoted influx macrophages early stage repair, improved dysfunctional inflammatory response, accelerated healing. vitro, damaged phagocytic functions M1-like induced by lipopolysaccharide (LPS), but not those M0-like PMA or M2-like interleukins 4 (IL-4) 13 (IL-13); impaired phagocytosis was rescued PM administration. These findings suggest increase metabolism vivo might contribute macrophage dysfunction, thereby affecting Our results indicate may be novel therapeutic approach treating wounds. forms protein adducts cause cell common diabetes. Pyridoxamine scavenges ameliorate this promoting could used therapeutically treat non-healing