L'R+-acido lipoico accelera la guarigione delle ulcere diabetiche sottoposte a terapia iperbarica: Modulazione dei fattori coinvolti nell'angiogenesi e nel rimodellamento tessutale

Chronic diabetic ulcer is characterised by a persistent inflammation followed by a high proteases concentration. Proteases lead to the degradation of growth factors and proteins of extracellular matrix which are important in the normal healing process. Up to date, the hyperbaric oxygen (HBO) therapy represents an alternative therapeutic approach. In this study, has been evaluated the effect of R⁺-lipoic acid in patients affected by chronic diabetic ulcers underwent to HBO therapy. By ELISA technique, the tissue and plasmatic concentration of factors involved in the angiogenesis and extracellular matrix remodelling have been evaluated. Patients underwent HBO therapy were included in two groups, the R⁺-lipoic acid group and the placebo group. Protein expression profiles for extracellular matrix and angiogenesis mediators were evaluated in biopsies and plasma samples collected at the first HBO session (T₀), at the 5^th HBO session (T₁) and after 10 days of HBO treatment (T₂). R ⁺-LA supplementation in combination with HBO therapy inhibits the chronic inflammatory state, changing the protease/anti-protease levels within the wound microenvironment. Decrease in the metalloproteinase-9 (MMP9) expression and the increase of metalloproteinase-2 (MMP2) together with increased levels of the piastrinic growth factor (PDGF-BB), significantly contribute to acceleration of the dermal wound repair process. Clinical analysis of the wounds show that R⁺-lipoic acid supplementation significantly reduce the wound area respect to the HBO treatment only (40.8 ± 37.2% vs 5.7 ± 43.3%, p = 0.02, respectively at day 42 of the treatment). In conclusion, R⁺-lipoic acid contributes to the disruption of the "positive autocrine feedback loops" that maintain the chronic wound state promoting the progression of the healing process.