BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS‐Treated Rats

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Abstract
Little is understood of skeletal muscle tissue in terms of oxidative stress and inflammation. Endothelin‐1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and proinflammatory cytokines. The aim of this study was to evaluate whether BQ123, an endothelin‐A receptor antagonist, influences the level of TNF‐α, IL‐6, SOD‐1, HO‐1, Nrf2 mRNA, and NF‐κB subunit RelA/p65 mRNA in the femoral muscle obtained from endotoxemic rats. Male Wistar rats were divided into 4 groups (n = 6) and received iv (1) saline (control), (2) LPS (15 mg/kg), (3) BQ123 (1 mg/kg), (4) BQ123 (1 mg/kg), and LPS (15 mg/kg, resp.) 30 min later. Injection of LPS led to significant increase in levels of RelA/p65 mRNA, TNF‐α, and IL‐6, while content of SOD‐1, HO‐1, and Nrf2 mRNA was unchanged. Administration of BQ123 prior to LPS challenge resulted in a significant reduction in RelA/p65 mRNA, TNF‐α, and IL‐6 levels, as well as markedly elevated concentrations of SOD‐1, HO‐1, and Nrf2 mRNA. BQ123 appears to enhance antioxidant defense and prevent production of TNF‐α and IL‐6 in skeletal muscle of LPS‐treated rat. In conclusion, endothelin‐A receptor antagonism exerts significant impact on the skeletal muscle favouring anti‐inflammatory effects and protection against oxidative stress.
Funding Information
  • Medical University of Lodz (503/0-079-03/503-01)

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