Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation

Abstract

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of Rheum palmatum L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague–Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways

“…Due to its toxicity to normal tissues, its clinical applications have been greatly limited. Thus, in recent years, efforts have been made to study Dox delivery systems to deliver drugs and reduce its toxicity and side effects on normal cells 15 – 17 .…”

Lactobacillus fermentumHFY06 reduced CCl4-induced hepatic damage in Kunming mice

“…AST is a transaminase marker for detecting liver injury. 2,14 Aer liver cells are damaged, enzymes such as AST are released into the blood. Therefore, detection of AST activity in the serum can accurately reect the degree of liver damage.…”

“…Studies have shown that CC1 4 -induced liver injury can be regulated or even restored to normal levels by the scavenging free radical enzyme, SOD. 2,4 Therefore, the antioxidant effect of HFY06 can be determined by determining the levels these important antioxidant-related genes. Compared with the model group, high-dose HFY06 upregulated Cu/Zn-SOD, Mn-SOD, and CAT mRNA expression, indicating that the free radicals produced by CCl 4 -induced liver oxidative metabolism can be eliminated.…”

“…It plays important roles in maintaining human health via oxidation, glycogen storage, detoxication, immunity, and protein secretion. [1][2][3] It is also susceptible to a range of stimuli, including viruses, toxins, drugs, alcohol and trauma, which can eventually lead to acute or chronic liver damage. 4,5 For example, excessive use of carbon tetrachloride (CCl 4 ) can cause severe liver damage, which may lead to liver failure and even death.…”

Chrysophanol Protects Against Acute Heart Failure by Inhibiting JNK1/2 Pathway in Rats

“…Chrysophanol, a member of the anthraquinone family, is a plant-derived herbal drug that is well known for its strong anti-inflammatory, anti-mutagenic, anti-microbial, hepatoprotective, and anti-carcinogenic activities [ 12 , 13 ]. Emerging evidence demonstrates that chrysophanol can alleviate the development of cardiovascular complications, such as diabetic cardiomyopathy [ 14 ], doxorubicin-induced cardiotoxicity [ 15 ], and isoproterenol-induced cardiac hypertrophy [ 16 ]. These pre-clinical studies have suggested the potential therapeutic value of chrysophanol in treating cardiac disease.…”