Jiajiu Yao, Zhen Qian, Xiaoxi Tian, Guoqiang Fu, Boliang Wang and Lihong Li
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 kg1) 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.
Jiajiu Yao, Zhen Qian, Xiaoxi Tian, Guoqiang Fu, Boliang Wang and Lihong Li, 2021. Involvement of BDNF Signalling Pathway in Spironolactone- Mediated Protective Effects in Sepsis-Induced Cardiac Injury in Rats. International Journal of Pharmacology, 17: 577-583.