Title:Active Immunization Against Tumor Necrosis Factor-alpha Decreases Proinflammatory Cytokines, Oxidative Stress Mediators and Adhesion Molecules Risk Factors in Streptozotocin-induced Diabetic Rats
Volume: 13
Issue: 3
Author(s): Muobarak J. Tuorkey, Karolin K. Abdul-Aziz and Abdel-Aziz A. Zidan
Affiliation:
Keywords:
Anti-tumor necrosis factor α, heat shock protein 70, intercellular adhesion molecules, vascular cell adhesion
molecules.
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.