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Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Aβ) induced oxidative stress and cognitive impairment in normal and diabetic rats.
Pharmacol Biochem Behav 2014; 120:65-72PB

Abstract

Alzheimer's disease (AD) is a progressive brain disorder leading to impairment of learning and memory. Amyloid β (Aβ) induced oxidative stress has been implicated in the initiation and progression of AD. Endothelin (ET) and its receptors have been considered as therapeutic targets for AD. Recent studies indicate that stimulation of ETB receptors may provide neuroprotection. The purpose of this study was to determine the preventative effect of selectively stimulating ETB receptors on cognitive impairment and oxidative stress in Aβ treated non-diabetic and diabetic (induced by streptozotocin) rats. Rats were concurrently treated with Aβ1-40 (day 1, 7 and 14) and either saline, IRL-1620 (an ETB agonist), and/or BQ788 (an ETB antagonist) daily for 14 days in the lateral cerebral ventricles using sterotaxically implanted cannula; experiments were performed on day 15. Aβ treatment produced a significant (p<0.0001) increase of 360% and 365% in malondialdehyde levels (a marker of lipid peroxidation) in non-diabetic and diabetic rats, respectively, compared to sham group. Antioxidants (superoxide dismutase and reduced glutathione) decreased following Aβ treatment compared to sham group. Treatment with IRL-1620 reversed these effects, indicating that ETB receptor stimulation reduces oxidative stress injury following Aβ treatment. In Morris swim task, Aβ treated rats showed impairment in spatial memory. Rats treated with IRL-1620 significantly reduced the cognitive impairment induced by Aβ. BQ788 treatment completely blocked IRL-1620 induced reduction in oxidative stress and cognitive impairment. Results of the present study demonstrate that IRL-1620 improved both acquisition (learning) and retention (memory) on water maze task and reduced oxidative stress parameters. It can be speculated that ETB receptor stimulation prevents cognitive impairment and may be useful in neurodegenerative diseases.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USA.Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA.Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USA. Electronic address: AGULAT@midwestern.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24561065

Citation

Briyal, Seema, et al. "Endothelin Receptor Type B Agonist, IRL-1620, Prevents Beta Amyloid (Aβ) Induced Oxidative Stress and Cognitive Impairment in Normal and Diabetic Rats." Pharmacology, Biochemistry, and Behavior, vol. 120, 2014, pp. 65-72.
Briyal S, Shepard C, Gulati A. Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Aβ) induced oxidative stress and cognitive impairment in normal and diabetic rats. Pharmacol Biochem Behav. 2014;120:65-72.
Briyal, S., Shepard, C., & Gulati, A. (2014). Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Aβ) induced oxidative stress and cognitive impairment in normal and diabetic rats. Pharmacology, Biochemistry, and Behavior, 120, pp. 65-72. doi:10.1016/j.pbb.2014.02.008.
Briyal S, Shepard C, Gulati A. Endothelin Receptor Type B Agonist, IRL-1620, Prevents Beta Amyloid (Aβ) Induced Oxidative Stress and Cognitive Impairment in Normal and Diabetic Rats. Pharmacol Biochem Behav. 2014;120:65-72. PubMed PMID: 24561065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Aβ) induced oxidative stress and cognitive impairment in normal and diabetic rats. AU - Briyal,Seema, AU - Shepard,Cortney, AU - Gulati,Anil, Y1 - 2014/02/20/ PY - 2013/06/21/received PY - 2014/01/20/revised PY - 2014/02/13/accepted PY - 2014/2/25/entrez PY - 2014/2/25/pubmed PY - 2014/12/15/medline KW - Alzheimer's disease KW - Beta amyloid KW - Cognitive impairment KW - ET(B) receptors KW - Endothelin KW - Oxidative stress SP - 65 EP - 72 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 120 N2 - Alzheimer's disease (AD) is a progressive brain disorder leading to impairment of learning and memory. Amyloid β (Aβ) induced oxidative stress has been implicated in the initiation and progression of AD. Endothelin (ET) and its receptors have been considered as therapeutic targets for AD. Recent studies indicate that stimulation of ETB receptors may provide neuroprotection. The purpose of this study was to determine the preventative effect of selectively stimulating ETB receptors on cognitive impairment and oxidative stress in Aβ treated non-diabetic and diabetic (induced by streptozotocin) rats. Rats were concurrently treated with Aβ1-40 (day 1, 7 and 14) and either saline, IRL-1620 (an ETB agonist), and/or BQ788 (an ETB antagonist) daily for 14 days in the lateral cerebral ventricles using sterotaxically implanted cannula; experiments were performed on day 15. Aβ treatment produced a significant (p<0.0001) increase of 360% and 365% in malondialdehyde levels (a marker of lipid peroxidation) in non-diabetic and diabetic rats, respectively, compared to sham group. Antioxidants (superoxide dismutase and reduced glutathione) decreased following Aβ treatment compared to sham group. Treatment with IRL-1620 reversed these effects, indicating that ETB receptor stimulation reduces oxidative stress injury following Aβ treatment. In Morris swim task, Aβ treated rats showed impairment in spatial memory. Rats treated with IRL-1620 significantly reduced the cognitive impairment induced by Aβ. BQ788 treatment completely blocked IRL-1620 induced reduction in oxidative stress and cognitive impairment. Results of the present study demonstrate that IRL-1620 improved both acquisition (learning) and retention (memory) on water maze task and reduced oxidative stress parameters. It can be speculated that ETB receptor stimulation prevents cognitive impairment and may be useful in neurodegenerative diseases. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/24561065/Endothelin_receptor_type_B_agonist_IRL_1620_prevents_beta_amyloid__Aβ__induced_oxidative_stress_and_cognitive_impairment_in_normal_and_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(14)00039-2 DB - PRIME DP - Unbound Medicine ER -