Targeting tumor necrosis factor alpha (TNF-α) in diabetic rats could approve avenues for an efficient strategy for diabetic therapy

• Published in: Diabetes & metabolic syndrome clinical research & reviews Vol. 6; no. 2; pp. 77 - 84
• Main Authors: Abdul-Aziz, Karolin K, Tuorkey, Muobarak J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2012
• Subjects: Animals; Blotting, Western; Chondrocytes - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Down-Regulation; Endocrinology & Metabolism; Forkhead box O-1 (FOXO-1); Forkhead Transcription Factors - drug effects; Immunohistochemistry; Interleukin-2 - pharmacology; Interleukin-6 - pharmacology; Male; Mucosa-associated lymphoid tissues (MALT); Myeloperoxidase (MPO); Nerve Tissue Proteins - drug effects; Oxidative Stress; Protein kinase B (Akt); Rats; Tumor necrosis factor α (TNF-α); Tumor Necrosis Factor-alpha - drug effects; Up-Regulation; Mucosa-associated lymphoid tissues (MALT); Tumor necrosis factor α (TNF-α); Myeloperoxidase (MPO); Forkhead box O-1 (FOXO-1); Protein kinase B (Akt)
• ISSN: 1871-4021; 1878-0334
• DOI: 10.1016/j.dsx.2012.08.004

Abstract Background Several studies held belief that downregulation of TNF-α may be effective for preventing diabetes and it's complications. However, it is not known whether TNF-α downregulation in long-term can generate any biological adverse. Aim The aim of the present study was to clarify what the impact is for such treatment with specific antibody for TNF-α on the other biological activities after 4 weeks. Methods Using western blot, IHC, Elisa, biochemical assays and scanning electron microscope. Results Results show that TNF-α, FOXO-1, IL-6 and MPO, when expressed in diabetic rats, collectively induce dramatic changes in diabetic rats. Since, TNF-α is involved in activation of transcription factor FOXO1 along with oxidative stress mediated by neutrophils. On one hand, IL-6 mediates neutrophils activation leading to an augmentation in stress mediators. And FOXO1 is activated in order to eliminate these oxidative mediators, on the other hand. Data show also that the prominent defect in mucosal IgA and IL-2 secretions may be the leading reasons for digestive atrophy. Finally, Akt-1 inhibits the cleavage of caspase 3, so, it could prevent the incidence of apoptosis. Conclusion Findings of this study reveal how TNF-α can be mechanistically coupled to greater diabetic complications potential.