Dataset Information

The chemopreventive potential of lycopene against atrazine-induced cardiotoxicity: modulation of ionic homeostasis.

ABSTRACT: People who drink water contaminated with atrazine (ATR) over many years can experience problems with their cardiovascular system. Lycopene (LYC) has been shown to exhibit cardiovascular disease preventive effects. However, chemopreventive potential of LYC against ATR-induced cardiotoxicity remains unclear. To determine the effects of ATR and/or LYC on heart, mice were treated with ATR (50?mg/kg or 200?mg/kg) and/or LYC (5?mg/kg) by intragastric administration for 21 days. Histopathological and biochemical analyses, including analysis of ion concentrations (Na(+), K(+), Ca(2+) and Mg(2+)), ATPases (Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase) activities and the transcription of their subunits, were performed on heart. The results revealed that ATR led to decreased Creative Kinase (CK) activity and increased histological alterations. Furthermore, a significant change in Na(+), K(+) and Ca(2+) content and the down-regulation of Na(+)-K(+)-ATPase and Ca(2+)-ATPase activities and the mRNA expression of their subunits were observed in ATR-exposed mice. Notably, supplementary LYC significantly protected the heart against ATR-induced damage. In conclusion, ATR induced cardiotoxicity by modulating cardiac ATPase activity and the transcription of its subunits, thereby triggering ionic disturbances. However, supplementary LYC significantly combated ATR-induced cardiotoxicity via the regulation of ATPase activity and subunit transcription. Thus, LYC exhibited a significant chemopreventive potential against ATR-induced cardiotoxicity.

SUBMITTER: Lin J

PROVIDER: S-EPMC4845055 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The chemopreventive potential of lycopene against atrazine-induced cardiotoxicity: modulation of ionic homeostasis.

Lin Jia J Li Hui-Xin HX Xia Jun J Li Xue-Nan XN Jiang Xiu-Qing XQ Zhu Shi-Yong SY Ge Jing J Li Jin-Long JL

Scientific reports 20160426

People who drink water contaminated with atrazine (ATR) over many years can experience problems with their cardiovascular system. Lycopene (LYC) has been shown to exhibit cardiovascular disease preventive effects. However, chemopreventive potential of LYC against ATR-induced cardiotoxicity remains unclear. To determine the effects of ATR and/or LYC on heart, mice were treated with ATR (50 mg/kg or 200 mg/kg) and/or LYC (5 mg/kg) by intragastric administration for 21 days. Histopathological and b ...[more]

PMID: 27112537

Similar Datasets

Project description:Shenmai injection (SMI), as a patented traditional Chinese medicine, is extracted from Panax ginseng and Ophiopogon japonicus. It commonly used in the treatment of cardiovascular disease and in the control of cardiac toxicity induced by doxorubicin (DOX) treatment. However, its anti-cardiotoxicity mechanism remains unknown. The purpose of this study was to investigate the underlying mitochondrial protective mechanisms of SMI on DOX-induced myocardial injury. The cardioprotective effect of SMI against DOX-induced myocardial damage was evaluated in C57BL/6 mice and H9c2 cardiomyocytes. In vivo, myocardial injury, apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt)/glycogen synthase kinase 3 beta (GSK-3β) signaling pathway related proteins were measured. In vitro, apoptosis, mitochondrial superoxide, mitochondrial membrane potential, mitochondrial morphology, levels of mitochondrial fission/fusion associated proteins, mitochondrial respiratory function, and AMP-activated protein kinase (AMPK) activity were assessed. To further elucidate the regulating effects of SMI on AMPK and PI3K/Akt/GSK-3β signaling pathway, compound C and LY294002 were utilized. In vivo, SMI decreased mortality rate, levels of creatine kinase, and creatine kinase-MB. SMI significantly prevented DOX-induced cardiac dysfunction and apoptosis, decreased levels of Bax/Bcl-2 and cleaved-Caspase3, increased levels of PI3K, p-Akt, and p-GSK-3β. In vitro, SMI rescued DOX-injured H9c2 cardiomyocytes from apoptosis, excessive mitochondrial reactive oxygen species production and descending mitochondrial membrane potential, which were markedly suppressed by LY294002. SMI increased ratio of L-OPA1 to S-OPA1, levels of AMPK phosphorylation, and DRP1 phosphorylation (Ser637) in order to prevent DOX-induced excessive mitochondrial fission and insufficient mitochondrial fusion. In conclusion, SMI prevents DOX-induced cardiotoxicity, inhibits mitochondrial oxidative stress and mitochondrial fragmentation through activation of AMPK and PI3K/Akt/GSK-3β signaling pathway.

Project description:Dose-dependent cardiotoxicity of doxorubicin may lead to irreversible congestive heart failure. Although multiple mechanisms are involved, generation of free radicals is the most commonly postulated mechanism. Therefore, free radical scavengers are considered as potential therapeutic agents. As Murraya koenigii leaves are a rich source of flavonoids and phenols, they have the ability to scavenge free radicals effectively. Therefore, the objective of this study was to investigate the cardioprotective potential of Murraya leaf extract against doxorubicin-induced cardiotoxicity in rats. Rats were randomly divided into five groups with 10 animals in each group. Doxorubicin was administered intraperitonially at 18?mg/kg while lyophilized plant extract was administered orally at 2?g/kg. Dexrazoxane, at 180?mg/kg, was used as the positive control. Cardiac damage of doxorubicin control was evident with a significant increase (p < 0.05) in cardiac troponin I, NT-pro BNP, AST, and LDH compared to the normal control. Plant-treated group showed cardioprotective effect by significantly reducing (p < 0.05) all of the above parameters compared to doxorubicin control (p < 0.05). Increased oxidative stress in doxorubicin control was evident with a significant reduction in reduced glutathione, glutathione reductase, glutathione peroxidase, total antioxidant capacity, superoxide dismutase, and catalase activity and a significant increase in lipid peroxidation compared to the control. Interestingly, treatment with Murraya leaf extract showed a significant increase in all of the above antioxidant parameters and a significant reduction in lipid peroxidation by showing an antioxidant effect. A significant increase in myeloperoxidase activity confirmed the increased inflammatory activity in doxorubicin control group whereas plant-treated group showed a significant reduction (p < 0.05) which expressed the anti-inflammatory effect of Murraya leaf extract. Doxorubicin-treated group showed histological evidence of extensive damage to the myocardium while plant-treated group showed a preserved myocardium with lesser degree of damage. Pretreatment with Murraya leaf extract may replenish cardiomyocytes with antioxidants and promote the defense against doxorubicin-induced cardiotoxicity.

Project description:Sugemule-3 (SD) is a traditional Chinese medicine with protective effect of myocardium. However, the underlying mechanisms of the effect had not been elucidated.In the present study, the serum of SD was prepared. A model of β-adrenergic agonist isoprenaline (ISO)-induced H9c2 cardiomyocytes injury was established in vitro. The changes in cell viability were examined to determine the available concentration of ISO and serum of SD. ELISA, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and flow cytometry were used to detect the effect of serum of SD on oxidative stress and apoptosis. The expression levels of the mitochondria-dependent apoptotic pathway and mitogen-activated protein kinase signalling-related proteins were analyzed.Incubation with different dose of ISO (0.015, 0.01, 0.005, and 0.0025 mol/L) for 24 h caused dose-dependent loss of cell viability and 0.01 mol/L of ISO approximately reduced the cell viability to 50%. Pretreatment with 50 μ mol/L serum of SD effectively decreased the levels of ISO-induced cell toxicity. Serum of SD relived ISO-induced oxidative stress and apoptosis in H9c2 cardiomyocytes. A further mechanism study indicated that serum of SD inhibited the mitochondria-dependent apoptotic pathways and regulated the expression levels of Bcl-2 family. ISO activated ERK and P38, whereas serum of SD inhibited their activation.Serum of SD inhibits the ISO-induced activation of the mitochondria-dependent apoptotic pathway, oxidative stress, and ERK, P38 inactivation. Serum of SD is used for the treatment of ISO-induced cardiomyopathy.The serum of SD pretreatment significantly ameliorated ISO-induced H9c2 cardiomyocytes injuries.The protective effect related with apoptosis and oxidative stressInhibition of MAPK pathway was involed in serum of SD induced cardioprotection.The serum of SD is used for the treatment of ISO-induced cardiomyopathy. Abbreviations used: ELISA: Enzyme-linked Immunosorbent Assay; TUNEL: TdT-mediated dUTP nick end labeling; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, DMSO: dimethyl sulfoxide; MDA: Malondialdehyde; SOD: Superoxide Dismutase; GSH-Px: Glutathione peroxidase.

Dataset Information

The chemopreventive potential of lycopene against atrazine-induced cardiotoxicity: modulation of ionic homeostasis.

Publications

The chemopreventive potential of lycopene against atrazine-induced cardiotoxicity: modulation of ionic homeostasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets