Involvement of BDNF Signalling Pathway in Spironolactone- Mediated Protective Effects in Sepsis-Induced Cardiac Injury in Rats

Background and Objective: Sepsis is one of the leading causes of mortality and myocardial injury is one of the major outcomes of sepsis. Recently, the renin-angiotensin-aldosterone modulating drug is reported to be useful in sepsis-induced cardiac injury. It is possible that spironolactone, an aldosterone receptor blocker, may attenuate sepsis-induced cardiac injury. The present study explored the beneficial effect and molecular mechanisms involved in spironolactone-mediated effects in sepsis-induced cardiac injury. Materials and Methods: Lipopolysaccharide (LPS) was employed to induce sepsis and cardiac injury in Wistar rats. The extent of myocardial injury was assessed by measuring the levels of cardiac troponin (cTnT) and CK-MB in plasma. The levels of inflammatory markers, IL-1 and anti-inflammatory, IL-10 were assessed as markers of inflammation. Treatment with spironolactone (25 and 50 mg kgG1 ) was done in sepsis-subjected rats. The levels of BDNF were measured to explore the molecular mechanism of spironolactone. The role of BDNF was further assessed by treating with BDNF blocker i.e. ANA-12 in spironolactone-treated rats. Results: Treatment with spironolactone significantly attenuated the sepsis-induced increase in cTnT and CK-MB levels in a dose-dependent manner. Moreover, it attenuated IL-1 and increased the levels of IL-10 in LPS-injected rats. It also restored a sepsis-induced decrease in the BDNF levels suggesting the key role of BDNF in spironolactone-mediated beneficial effects. Co-administration of ANA-12 abolished the inflammatory actions of spironolactone and protective effects in the sepsis-induced heart injury model. Conclusion: Spironolactone may be effective in attenuating sepsis-induced cardiac injury and its protective effects may be possibly due to due to increase in the BDNF levels.