The influence of ETA and ETB receptor blockers on LPS-induced oxidative stress and NF-κB signaling pathway in heart.
Gen Physiol Biophys
; 31(3): 271-8, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-23047940
ABSTRACT
The aim of this study was to assess whether an endothelin-A receptor (ETA-R) blocker, BQ123, or an endothelin-B (ETB-R) receptor blocker, BQ788, influences nuclear factor kappa beta (NF-κB) pathway, free radical generation, tumor necrosis factor-alpha (TNF-α) concentration, and glutathione redox system in hearts obtained from lipopolysaccharide (LPS)-induced endotoxic rats. The study was performed on rats divided into groups 1) saline, 2) saline + LPS (15 mg/kg), 3) BQ123 (1 mg/kg b.w.) + LPS, 4) BQ123 (0.5 mg/kg b.w.) + LPS, 5) BQ788 (3 mg/kg b.w.) + LPS. The ETA-R and ETB-R antagonists were injected i.v. 30 min before LPS administration. In rats, BQ123 caused a significant decrease in TBARS (p < 0.05) but not in H2O2 concentration. It also decreased tissue protein level and improved tissue redox status (p < 0.01). Only a dose of 1 mg/kg decreased TNF-α concentration (p < 0.05). BQ788 lowered TBARS, H2O2 and protein concentration (p < 0.05; p < 0.02; p < 0.001, respectively), however, it did not affect TNF-α concentration. Neither ETA-R nor ETB-R blockers influenced LPS-induced increase in p65 subunit level and activation of NF-κB pathway. Our results demonstrated that ETA-R blockage is more effective in inhibiting free radical generation and improving heart antioxidant properties than ETB-R blockage under oxidative stress. NF-κB pathway is not incorporated in ETA-R and ETB-R influence on ROS production.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Lipopolisacáridos
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FN-kappa B
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Estrés Oxidativo
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Antagonistas de los Receptores de la Endotelina A
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Antagonistas de los Receptores de la Endotelina B
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Miocardio
Límite:
Animals
Idioma:
En
Revista:
Gen Physiol Biophys
Año:
2012
Tipo del documento:
Article
País de afiliación:
Polonia