Speaker at Pharmaceutics and Drug Delivery Systems 2022 - Amira Zaky
Alexandria University, Egypt
Title : APE-1 redox activity inhibition impacts dopaminergic system in inflammatory pain condition

Abstract:

Apurinic/Apyrimidinic Endonuclease 1/Redox Effector- 1 (APE1/Ref-1) is a negative regulator of inflammatory response via several mechanisms in neuronal cells. APE1’s redox activity stimulates the DNA-binding activity of several transcription factors. We investigated targeting the APE1 redox activity that might influence the neurotransmitters and related receptors by intradermal injection of E3330 (selective redox inhibitor of APE1) in formalin- induced rat inflammatory pain model. Accumulating evidence has shown that dopamine systems in the brain are also involved in the central regulation of chronic pain. Most importantly, descending dopaminergic pathways play an important role in pain modulation. Therefore, we tested the effect of APE1 redox activity on the regulation of dopaminergic signaling pathway. We determined the index of pain through behavioral tests after peripheral induction of formalin (50µl in the dorsal surface of hindpaw). Interestingly, our data point to a decreased nuclear accumulation of APE1 mRNA expression, changed its distribution in the inflamed group as compared to the sham group (i.e. reduced IL-6 expression) and alleviated pain, as assessed by measuring the paw edema.  In support to our results, the study of Pacheco, 2017 reported that high-dopamine levels promote the stimulation of low affinity dopamine receptors including, DRD1, DRD2 and DRD4, inducing anti-inflammatory effect in microglia, while low dopamine levels selectively stimulate high-affinity dopamine receptors including, DRD3 and DRD5, triggering inflammation. In conclusion, inhibition of the Redox function by E3330 compound might constitute a novel approach for treating inflammatory pain through modulating the level of dopamine and the affinity of its D5R and D2R receptors inside spinal cord.

Biography:

Dr. Amira Zaky studied Biochemistry at Alexandria University, Egypt and graduated in 1999. She then joined the research group of Prof. Ahmad Bassiouny at the Department of Biochemistry, Faculty of Science-Alexandria University. She received her master degree in 2003. She Received her PhD degree in 2007 at the same institution, through sandwich program between Alexandria University and University of Texas Medical Branch (UTMB) in USA. In 2014 she promoted to assistant professor in the same department, then to full professor in 2020. Dr. Amira published 18 articles in SCI (E) journals. She was elected as African regional committee member in the international Brain Research Organization (IBRO-ARC) since 2016.

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