Abstract
The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we evaluated the healing effects of a new zinc complex, [Zn(phen)(van)2], identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 μmol cm-2 (CS-ZPV1) and 1.22 μmol cm-2 (CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in Wistar rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1β, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-β and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1β as well as increased IL-10 and gene expression of TGF-β and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds.
Highlights
Diabetes mellitus is a serious disease characterized by high levels of glucose plasma, and it represents a serious public health problem with negative impacts on the quality of life of patients
The[Zn(phen)(van)2] (ZPV) complex was obtained by substitution of the chloride ligands in the precursor by two bidentate vanillate ligands originating from an octahedral complex where the methoxy groups of the vanillate ions are disposed opposite to each other in a structural arrangement identified previously as cis-III
The preparation of chitosan (CS) membranes modified with [Zn(phen)(van)2] complex, identified in this work as CS-ZPV, was performed by a condensation reaction between the aldehyde groups of the vanillin ligand and the amine groups distributed in the chitosan structure originating from a Schiff base
Summary
Diabetes mellitus is a serious disease characterized by high levels of glucose plasma, and it represents a serious public health problem with negative impacts on the quality of life of patients. Hyperglycaemia has toxic effects on many cells in the body, contributing to the appearance of acute and chronic complications associated with the disease. Diabetic foot ulcers are a complication with high incidence usually involved with hospitalizations, and they can often lead to lower-extremity amputations. Diabetic patients present late or poor wound healing, and elevated glucose may induce oxidative stress and activate inflammatory response capacity for the development of diabetic neuropathy. Diabetics with a diabetic neuropathy are more likely to develop serious wounds with complications (Falanga, 2005)
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