Active Immunization Against Tumor Necrosis Factor-alpha Decreases Proinflammatory Cytokines, Oxidative Stress Mediators and Adhesion Molecules Risk Factors in Streptozotocin-induced Diabetic Rats

Author(s): Muobarak J. Tuorkey, Karolin K. Abdul-Aziz, Abdel-Aziz A. Zidan.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets

Volume 13 , Issue 3 , 2013

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Abstract:

Diabetes is now one of the most common un-communicable diseases worldwide. Few studies have dealt specifically with the potential therapeutic effect of TNF-α suppressor to decrease oxidative stress markers in patients with diabetes. The aim of this study was to investigate the potential therapeutic and toxic effect of the direct injection of the anti-TNF-α on oxidative stress mediators, proinflammatory cytokines and vascular risk factors associated with diabetes on diabetic rats. Methods: diabetes was induced by streptozotocin, three weeks after the – induction of diabetes, a polyclonal anti-mouse/rat TNF-α rabbit serum was injected in the treated group and sacrificed after 4 weeks. The expression of TNF-α  mRNA was measured by RT-PCR. The levels of TNF-α, VEGF, IL-2, IL- 6, HSP-70, troponin-t, 8-OHdG, ICAM-1 and VCAM-1 were evaluated using ELISA. Myeloperoxiase (MPO) and total peroxides (TPs) levels were estimated by biochemical reactions. Results: the treatment of diabetic rats with the anti-TNF-α caused a significant decrease in the TNF-α mRNA expression, which were paralleled with the decreased levels of TNF-α, IL-6, MOP, HSP-70, ICAM-1, VCAM-1, troponin-t and 8-OHdG in the blood serum. On the contrary, all were highly expressed in the diabetic group that may be the leading reasons for the DNA damage and cell loss. Data revealed that TNF-α, HSP-70, IL-6, MPO and adhesion molecules when expressed in diabetic rats, collectively induce dramatic changes. Conclusion: these new findings suggested that targeting TNF-α could effectively reduce expressions of MCP-1, HSP-70, troponin-t, 8-OHdG and VCAM- 1, along with prominent reduction in MPO and IL-6 levels.

Keywords: Anti-tumor necrosis factor α, heat shock protein 70, intercellular adhesion molecules, vascular cell adhesion molecules.

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Article Details

VOLUME: 13
ISSUE: 3
Year: 2013
Page: [269 - 274]
Pages: 6
DOI: 10.2174/18715303113139990039
Price: $58

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