Journals Proceedings

Abstract

ET-1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and pro-inflammatory cytokines. The purpose of this study was to investigate the effect of JSH-23 (inhibitor of NF-κB pathway) on ET-1 induced oxidative stress and inflammation, and whether this actions is associated with activation of Nrf2 pathway. Experiments were performed on rats. The animals were randomly divided into four groups: Group 1 (control group): received two doses of 0.2 ml saline, 0.5 h apart. Group 2 (saline + ET-1 group; served as ET-1 control): the rats were given 0.2 ml saline and ET-1 (8 μg/kg) 0.5 h later. Group 3 (saline + JSH-23): rats received 0.2 ml of JSH-23 (2mg/kg) and 30 min later 0.2 ml of saline. Group 4 (JSH- 23+ET-1): rats received a single dose of JSH-23 (2 mg/kg) and a single dose of ET-1 (8 μg/kg) after 0.5 h. ET-1 administration caused increase in TNF–α level and expression of subunit p65 NF-κB and decrease in SOD-1 level and Nrf2 expression. However, JSH-23 inhibited ET-1- induced increased in TNF-α, expression of subunit NF-κB p65 and enhanced level of SOD-1 and expression of Nrf2. JSH-23 inhibited oxidative stress and inflammation by inhibited NF-κB pathway, activation pathway of Nrf2 and increase in SOD-1level.