Anti-apoptosis effects on hearts of SHSST cyclodextrin complex in a carbon tetrachloride-induced cirrhotic cardiomyopathy rat model.

ABSTRACT

Cirrhotic cardiomyopathy (CCM) is a common cardiac dysfunction in patients waiting for orthotopic liver transplantation (OLT). Carbon tetrachloride (CCl4) intraperitoneal (IP) injection has been reported as successful in a cirrhosis-induced CCM model. In this work, we used the same assay for CCM induction using CCl4 (0.2 mg/kg) IP injection twice per day for 14 days during the cardiac protection drugs treatment process. The cardiac protection drugs were silymarin (100 mg/kg/day), baicalein (30 mg/kg/day), San Huang Shel Shin Tang (SHSST, 30 mg/kg/day) and ß-cyclodextrin modified SHSST (SHSSTc, 30 mg/kg/day and 300 mg/kg/day). After 4 weeks of treatment, the SHSSTc cardiac protection effects were determined through activation of the IGF1R cell survival pathway and inhibition of Fas-FADD death domain induced-apoptosis. SHSSTc cardiac protection was enhanced through ß-cyclodextrin modification, which increased bio-availability, and displayed stronger protective effects than silymarin and baicalein, both of which are well-known liver protection drugs. Thus, SHSSTc might provide the best therapeutic benefit in CCM treatment.