Oral administration of antioxidants improves skin wound healing in diabetic mice.
Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b+and Ly6G+cells) and reduced levels of KC, TNF-α, IL-1β, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG+/CD206-macrophages whereas CD206+/MIG-macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Ana Flávia Marçal
AF
Pessoa
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Juliana Costa
JC
Florim
School of Applied Sciences, University of Campinas, Limeira, Brazil.
Hosana Gomes
HG
Rodrigues
Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Vinicius
V
Andrade-Oliveira
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Simone A
SA
Teixeira
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil, and.
Kaio Fernando
KF
Vitzel
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil, and.
Rui
R
Curi
Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Niels Olsen
NO
Saraiva Câmara
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Marcelo N
MN
Muscará
Department of Morphological Sciences, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Marcelo Lazzaron
ML
Lamers
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Marinilce Fagundes
MF
Santos
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000473:pathology*
D000975:Antioxidants; D001786:Blood Glucose; D053762:Interleukin-12 Subunit p40; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D013482:Superoxide Dismutase