ERK activation by zeranol has neuroprotective effect in cerebral ischemia reperfusion.

Abstract

AIMS:

Incidence of stroke increases in postmenopausal women with dangerous consequences. In this study we used zeranol to protect ovariectomized (OVX) rats against cerebral I/R damage and our target is to identify the mechanism of its protection, in addition to investigating whether this mechanism inhibits inflammation (by preventing glial cell activation) and apoptosis.

MAIN METHODS:

First 18 ovariectomized rats were allocated into 3 groups: I/R group, zeranol+ I/R group and U0126, MEK1/2 inhibitor + zeranol+ I/R group. After 24 h reperfusion, protein expression of total extracellular signal-regulated protein kinase (t-ERK1/2), phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2), Bcl-2, and Bax were quantified. Second 36 female rats were allocated into 3 groups: sham group, I/R group (after ovariectomy by 7 weeks, rats exposed to cerebral I/R) and zeranol group (after ovariectomy by 2 weeks, rats received zeranol for 5 weeks). After 24 h of reperfusion, the following parameters were measured; total nitrate/nitrite, interleukin-10, myeloperoxidase, caspase-3, and finally immunohistochemistry analysis of glial fibrillary acidic protein, cyclooxygenase-2 in cortex and hippocampus (CA1) regions were performed.

KEY FINDINGS:

U-0126 administration reversed the neuroprotective effect induced by zeranol through decreasing ratio of p-ERK1/2:ERK1/2 and Bcl-2/Bax in brain tissue. Activation of ERK signaling pathway by zeranol caused reduction in brain apoptosis and inflammation.

SIGNIFICANCE:

Zeranol showed protective effect in OVX rats that were exposed to cerebral I/R by activation of ERK signaling pathway which was blocked by U0126. This protective effect in turns led to decrease inflammation and apoptosis.

• Authors: Shimaa K Mohamed, Amany A E Ahmed, Engy M Elmorsy, Shahira Nofal
• Journal: Life sciences (Life Sci) Vol. 227 Pg. 137-144 (Jun 15 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31005550 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Neuroprotective Agents
• Zeranol
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Apoptosis (drug effects)
• Brain (metabolism)
• Brain Ischemia (drug therapy)
• Cerebral Infarction
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Hippocampus (metabolism)
• MAP Kinase Signaling System (drug effects)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neuroprotective Agents (metabolism, pharmacology)
• Ovariectomy
• Rats
• Rats, Wistar
• Reperfusion
• Reperfusion Injury (prevention & control)
• Signal Transduction (drug effects)
• Zeranol (metabolism, pharmacology)