Effect of Aminoguanidine Intervention on Neutrophils in Diabetes Inflammatory Cells Wound Healing

Abstract

To explore aminoguanidine (AG) effect on neutrophil functions and associated signal transduction way in diabetic rats wound healing. Sprague-Dawley (SD) rats were divided into 3 groups, Group A (control+burns), Group B (diabetes+burns), Group C (diabetes+burns+AG). Wound skin tissue was harvested at 6h, 24h and 36h after trauma, and then immunohistochemistry was used to detect AGE (advanced glycation end products) contents and RAGE (receptor of AGE) expression. Western blotting was applied to detect RAGE and NF-κB. Oxidative stress changes were detected by colorimetry. Inflammatory cytokines were determined by ELIASA and cell apoptosis by TUNEL. Pathological changes were analyzed by hematoxylin-eosin (HE) staining. In the wound tissue of Group C, compared to that in Group B, AGE content, RAGE expression level, NF-κB level declined, and MPO (myeloperoxidase) decreased at 36h; TNFα, IL-8, H2O2, GSH-Px (Glutathione peroxidse), and MDA (malondialdehyde) levels increased; dense post-traumatic inflammation belt formed obviously. AG for prophylactic use can promote the migration and respiratory burst of neutrophils markedly, and help to restore the functions of neutrophil; and the abnormal secretion of inflammation cytokines can be corrected partly. Blocking AGE deposition and promoting microenvironment were effective ways for diabetic wound healing.

Key words

aminoguanidine - neutrophils - diabetic wound healing

^# Co-first author: These authors contributed equally to this work.

• References

• 1 Fernando WA, Leininger E, Simkin J et al. Wound healing and blastema formation in regenerating digit tips of adult mice. Developmental biology 2011; 350: 301-310
• 2 Dovi JV, He L-K, Dipietro LA. Accelerated wound closure in neutrophil-depleted mice. Journal of leukocyte biology 2003; 73: 448-455
• 3 Pradhan L, Cai X, Wu S et al. Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. Journal of Surgical Research 2011; 167: 336-342
• 4 Medina A, Scott PG, Ghahary A et al. Pathophysiology of chronic nonhealing wounds. Journal of Burn Care & Research 2005; 26: 306-319
• 5 Zimmet P. Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted?. Journal of internal medicine 2000; 247: 301-310
• 6 Touré F, Zahm JM, Garnotel R et al. Receptor for Advanced Glycation end products (RAGE) modulates neutrophil adhesion and migration on Glycoxidated extracellular matrix. Biochemical Journal 2010; 416: 255-261
• 7 Toyoda F, Kakehashi A, Ota A et al. Prevention of proliferative diabetic retinopathy and cataract in SDT rats with aminoguanidine, an anti-advanced glycation end product agent. Open Diabetes Journal 2011; 4: 108-113
• 8 Jakuš V, Bauerová K, Rietbrock N. Effect of aminoguanidine and copper (II) ions on the formation of advanced glycosylation end products. Arzneimittelforschung 2011; 51: 280-283
• 9 Ozturk A, Fırat C, Parlakpınar H et al. Beneficial Effects of Aminoguanidine on Skin Flap Survival in Diabetic Rats. Experimental diabetes research 2012; 2012
• 10 Guimarães R, De Oliveira P, Oliveira A. Effects of induced diabetes and the administration of aminoguanidine in the biomechanical retention of implants: a study in rats. Journal of periodontal research 2011; 46: 691-696
• 11 Walker HL, Mason Jr AD. A Standard animal burn. The Journal of Trauma and Acute Care Surgery 1968; 8: 1049-1051
• 12 Gado A, Yassen A. Protective Effect Of Thymoquinone And Aminoguanidine Against Bleomycin Induced Lung Damage: Possible Role Of Nitric Oxide Synthase. The Internet Journal of Toxicology. 2012: 8
• 13 Brindicci C, Ito K, Torre O et al. Effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, on nitric oxide production and its metabolites in healthy control subjects, healthy smokers, and COPD patients. CHEST Journal 2009; 135: 353-367
• 14 Naso FCD, Forgiarini Jr LA, Forgiarini LF et al. Aminoguanidine reduces oxidative stress and structural lung changes in experimental diabetes mellitus. Jornal Brasileiro de Pneumologia 2010; 36: 485-489
• 15 Pase L, Layton JE, Wittmann C et al. Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish. Current Biology. 2012
• 16 Villeneuve LM, Natarajan R. The role of epigenetics in the pathology of diabetic complications. American Journal of Physiology-Renal Physiology 2010; 299: F14-F25
• 17 Giardino I, Fard AK, Hatchell DL et al. Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis. Diabetes 1998; 47: 1114-1120
• 18 Niu Y, Xie T, Ge K et al. Effects of extracellular matrix glycosylation on proliferation and apoptosis of human dermal fibroblasts via the receptor for advanced glycosylated end products. The American Journal of Dermatopathology 2008; 30: 344-351
• 19 Fu X, Cheng B, Sheng Z. Growth factors and wound healing: review and prospect in recent ten years. Zhongguo xiu fu chong jian wai ke za zhi=Zhongguo xiufu chongjian waike zazhi=Chinese journal of reparative and reconstructive surgery 2004; 18: 508
• 20 Niu Y-W, Xie T, Ge K et al. Effects of FGF_2 on wound healing process in diabetic rats with second-degree scald [J]. Journal of Shanghai Jiaotong University (Medical Science) 2009; 2: 002
• 21 Yi-Wen N, Ting X, Kui G et al. Effects of FGF2 on wound healing process in diabetic rats with second-degree scald. Journal of Shanghai Jiaotong University (Medical Science) 2009; 29: 121-125