Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats

Abstract

Background/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is protective against some cardiovascular diseases. In this study, we aimed to investigate the effects of oxymatrine on doxorubicin-induced cardiotoxicity in rat hearts and H9c2 cells. Methods: Creatine Kinase - MB (CK-MB) and Lactate Dehydrogenase (LDH) levels were determined using commercial kits. Biochemical indices reflecting oxidative stress, such as catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also analyzed with commercial kits. Mitochondrial reactive oxygen species (ROS) 2’,7’-dichlorofluorescin diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes, and apoptosis was measured using a commercial kit. Western blots were used to detect the level of expression of cleaved caspase-3. Results: Doxorubicin treatment significantly increased oxidative stress levels, as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Doxorubicin also increased pathological damage in myocardial tissue, myocardial ROS levels, and malonyldialdehyde levels, and induced apoptosis in myocardial tissues and H9c2 cells. All of these doxorubicin-induced effects were attenuated by oxymatrine. Conclusion: These in vitro and in vivo findings indicate that oxymatrine may be a promising cardioprotective agent against doxorubicin-induced cardiotoxicity, at least in part mediated through oxymatrine’s inhibition of cardiac apoptosis and oxidative stress.

Klotho Improves Cardiac Function by Suppressing Reactive Oxygen Species (ROS) Mediated Apoptosis by Modulating Mapks/Nrf2 Signaling in Doxorubicin-Induced Cardiotoxicity

“…Several rats were exposed to DOX (3 mg/kg, Sigma-Aldrich) by intraperitoneal injections (single dose of DOX every another day for total three injections) [ 17 ]. Recombinant klotho protein (0.01 mg/kg, R&D) was administrated to rats by intraperitoneal injections every another day for total two injections [ 16 ].…”

“…Then the cells were maintained in MEM containing bovine serum albumin (0.1 mg/mL, Gibco), L-glutamine (2 mmol/L, Gibco) and antibiotics mix (Sigma-Aldrich) in a cell incubator providing humidified environment, constant temperature at 37°C and fresh air (5% CO 2 ). DOX (1 μmol/L for 24 hours) [ 17 ], klotho (400 pmol/L, four hours prior to DOX exposure) [ 23 ], specific MAPKs inhibitors and specific small interference RNAs (siRNA) against genes MAPKs were used to incubate the isolated myocytes. Control cells were incubated with MEM.…”

Safety and Efficacy Evaluation of Traditional Chinese Medicine (Qingre‐Lishi‐Yishen Formula) Based on Treatment of Regular Glucocorticoid Combined with Cyclophosphamide Pulse in Children Suffered from Moderately Severe Henoch–Schonlein Purpura Nephritis with Nephrotic Proteinuria

“…Furthermore, it is proved by Chen et al that the anti-hypertensive active of Radix Paeoniae Alba extract may be related to its effect on regulating serum nitric oxide and endothelin levels [38]. Oxymatrine, one of the principle components of Radix Sophorae Flavescentis, was demonstrated in vitro and in vivo by Zhang et al that may be a promising cardioprotective agent in part through inhibition of cardiac apoptosis and oxidative stress [39].…”

Oxymatrine Reverses Gentamicin-Induced Nephrotoxicity via Ameliorating the Immune Response for Gentamicin Therapy

“…Previous studies have shown that OXY preprocessing deduced level of ROS production in renal tissue caused by ischemia/reperfusion and activated serum antioxidant enzyme activities. Oxymatrine also ameliorated pathological damage in myocardial tissue induced by doxorubicin with anti-oxidative and anti-inflammatory effects [23,24]. Furthermore, oxymatrine has been shown to improve microcirculation and liver function [24].…”

“…Oxymatrine also ameliorated pathological damage in myocardial tissue induced by doxorubicin with anti-oxidative and anti-inflammatory effects [23,24]. Furthermore, oxymatrine has been shown to improve microcirculation and liver function [24]. Previous studies identified that the mitochondrial dysfunction [27,28], apoptosis/necrosis [29,30] and inflammation [31] are also included in gentamicin-induced kidney injury in rats and human renal proximal tubular cells (HKC).…”