Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes

Abstract

The effect of Schisandra fructus extract (SFE) on doxorubicin (Dox)-induced cardiotoxicity was investigated in H9c2 cardiomyocytes. Dox, which is an antineoplastic drug known to induce cardiomyopathy possibly through production of reactive oxygen species, induced significant cytotoxicity, intracellular reactive oxygen species (ROS), and lipid peroxidation. SFE treatment significantly increased cell survival up to 25%, inhibited intracellular ROS production in a time-and dosedependent manner, and inhibited lipid peroxidation induced by Dox. In addition, SFE treatment induced expression of cellular glutathione S-transferases (GSTs), which function in the detoxification of xenobiotics, and endogenous toxicants including lipid peoxides. Analyses of 31,100 genes using Affymetrix cDNA microarrays showed that SFE treatment up-regulated expression of genes involved in glutathione metabolism and detoxification [GST theta 1, mu 1, and alpha type 2, heme oxygenase 1 (HO-1), and microsomal epoxide hydrolase (mEH)] and energy metabolism [carnitine palmitoyltransferase-1 (CPT-1), transaldolase, and transketolase]. These data indicated that SFE might increase the resistance to cardiac cell injury by Dox, at least partly, together with altering gene expression, especially induction of phase II detoxification enzymes.

Sesamol prevents doxorubicin-induced oxidative damage and toxicity on H9c2 cardiomyoblasts

“…The observed GSH deficiency and elevated GSSG levels in the DOX group might be due to GSH consumption in the interactions of DOX‐induced free radicals with bio‐membrane and the subsequent lipid peroxidation. Clearly, these data indicate the occurrence of oxidative stress, which is in accordance with reports of previous studies . Pre‐treatment of H9c2 cells with sesamol significantly guarded against the oxidative stress observed in the DOX group.…”

“…Clearly, these data indicate the occurrence of oxidative stress, which is in accordance with reports of previous studies. [63,64] Pretreatment of H9c2 cells with sesamol significantly guarded against the oxidative stress observed in the DOX group.…”

Protective effect of bilberry (Vaccinium myrtillus) against doxorubicin-induced oxidative cardiotoxicity in rats

“…Clearly, these data indicate the occurrence of oxidative stress, which is in accordance with reports of previous studies [32,33]. The reduced GSH and the elevated GSSG levels in the DOX group might be due to GSH consumption in the interactions of DOX-induced free radicals with bio-membrane and the subsequent lipid peroxidation.…”

Chronic Anthracycline Cardiotoxicity: Molecular and Functional Analysis with Focus on Nuclear Factor Erythroid 2-Related Factor 2 and Mitochondrial Biogenesis Pathways

“…So far, very little and rather variable data are available regarding HO1 and ANT cardiotoxicity, and virtually nothing has been reported regarding the clinically relevant chronic forms resulting in heart failure. Using proliferating H9c2 cells, a suppression of HO1 expression has been reported after in vitro ANT treatment (Bernuzzi et al, 2009), whereas others have suggested the opposite in a microarray study (Choi et al, 2008). Little to no change in HO1 expression has been seen at protein and mRNA levels 2 weeks after a single supratherapeutic ANT dose (Suliman et al, 2007) and 70 days after injection of 1 mg/kg for 10 days (Richard et al, 2011), respectively.…”