Cardioprotective Potential of Celastrol In Sepsis-induced Cardiotoxicity: Mouse Model of Endotoxemia

Assessment of cardio-protective potential of celastrol against sepsis-induced cardiac injury in mice.

A twenty- four Swiss albino mice aged between 6-8 wks., weighted between 20-30 g were included in this study. They were randomly divided into 4 groups, each of 6:Sham group: laparotomy without cecal ligation and puncture( CLP), Sepsis group: (laparotomy with CLP), Vehicle group: Treated with equivalent volume of DMSO i.p. 1 hr. before CLP, Celastrol treated group: treated with 2 mg/kg  i.p. 1 hr before CLP. Animals were sacrificed after 24 hrs. Blood samples then aspirated for assessment of cardiac troponin and CK-MB by spectrophotometric assay. Part of cardiac tissue was used for assessment of the levels of TNF, IL6, IL10, F2-Isoprostane, and TLR4 by ELISA method, another part was used  for assessment of the degree of cardiac tissue damage by histo-pathological analysis.

Significant cardiac damage was noticed in sepsis group (P≤ 0.05) as compared with sham group manifested by significant elevation in inflammatory markers( TNF, IL6, TLR4) and oxidative stress marker( F2-Isoprostane) as well as cardiac troponin and CK-MB, with significant reduction in IL10.
Pretreatment with celastrol was resulted in significant reduction in TNF,IL6, TLR4,  F2-Isoprostane, troponin,  and CK-MB with significant elevation in IL10 as compared to sepsis group.
In the same manner significant histological damage was encountered in sepsis group as compared to sham, while celastrol treated group exhibit minor histological damage as compared to sepsis group.

Celastrol have a cardio-protective effects against cardiac injury induced by endotoxemia.