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ERK activation by zeranol has neuroprotective effect in cerebral ischemia reperfusion.
Life Sci. 2019 Jun 15; 227:137-144.LS

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+Show Affiliations

Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt. Electronic address: shimaa_kamal@pharm.helwan.edu.eg.Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31005550

Citation

Mohamed, Shimaa K., et al. "ERK Activation By Zeranol Has Neuroprotective Effect in Cerebral Ischemia Reperfusion." Life Sciences, vol. 227, 2019, pp. 137-144.
Mohamed SK, Ahmed AAE, Elmorsy EM, et al. ERK activation by zeranol has neuroprotective effect in cerebral ischemia reperfusion. Life Sci. 2019;227:137-144.
Mohamed, S. K., Ahmed, A. A. E., Elmorsy, E. M., & Nofal, S. (2019). ERK activation by zeranol has neuroprotective effect in cerebral ischemia reperfusion. Life Sciences, 227, 137-144. https://doi.org/10.1016/j.lfs.2019.04.035
Mohamed SK, et al. ERK Activation By Zeranol Has Neuroprotective Effect in Cerebral Ischemia Reperfusion. Life Sci. 2019 Jun 15;227:137-144. PubMed PMID: 31005550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ERK activation by zeranol has neuroprotective effect in cerebral ischemia reperfusion. AU - Mohamed,Shimaa K, AU - Ahmed,Amany A E, AU - Elmorsy,Engy M, AU - Nofal,Shahira, Y1 - 2019/04/18/ PY - 2019/02/05/received PY - 2019/04/02/revised PY - 2019/04/15/accepted PY - 2019/4/22/pubmed PY - 2019/6/5/medline PY - 2019/4/22/entrez KW - Apoptosis KW - Cerebral ischemia reperfusion KW - ERK1/2 KW - Inflammation KW - U0126 KW - Zeranol SP - 137 EP - 144 JF - Life sciences JO - Life Sci VL - 227 N2 - 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31005550/ERK_activation_by_zeranol_has_neuroprotective_effect_in_cerebral_ischemia_reperfusion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30291-7 DB - PRIME DP - Unbound Medicine ER -