Exogenous fetuin‐A protects against sepsis‐induced myocardial injury by inhibiting oxidative stress and inflammation in mice

Abstract Sepsis‐induced myocardial injury is a consequence of septicemia and is one of the major causes of death in intensive care units. A serum glycoprotein called fetuin‐A is secreted largely by the liver, tongue, placenta, and adipose tissue. Fetuin‐A has a variety of biological and pharmacological properties. The anti‐inflammatory and antioxidant glycoprotein fetuin‐A has shown its efficacy in a number of inflammatory disorders including sepsis. However, its protective role against sepsis‐induced myocardial injury remains elusive. The purpose of this work is to explore the role of fetuin‐A in mouse models of myocardial injury brought on by cecal ligation and puncture (CLP). CLP significantly induced the myocardial injury assessed in terms of elevated myocardial markers (serum CK‐MB, cTnI levels), inflammatory markers (IL‐6, TNF‐α) in the serum, and oxidative stress markers (increased MDA levels and decreased reduced glutathione) in heart tissue homogenate following 24 h of ligation and puncture. Further, hematoxylin and eosin (H&E) staining showed considerable histological alterations in the myocardial tissue of sepsis‐developed mice. Interestingly, fetuin‐A pretreatment (50 and 100 mg/kg) for 4 days before the CLP procedure significantly improved the myocardial injury and was evaluated in perspective of a reduction in the CK‐MB, cTnI levels, IL‐6, and TNF‐α in sepsis‐developed animals. Fetuin‐A pretreatment significantly attenuated the oxidative stress and improved the myocardial morphology in a dose‐dependent manner. The present study provides preliminary evidence that fetuin‐A exerts protection against sepsis‐induced cardiac dysfunction in vivo via suppression of inflammation and oxidative damage.