ArticleToxicology and applied pharmacology2015
Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice.
Article in Toxicology and applied pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Pervasive environmental contaminant acrolein compromises myocardial geometry and function through the induction of cuproptosis.Acta biochimica et biophysica Sinica · 2025Article
- GSTP1 inhibits angiotensin II-induced atrial fibrillation by regulating ferroptosis.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- Gene polymorphisms associated with immunosuppressant adverse effects in systemic lupus erythematosus: a narrative review.Frontiers in genetics · 2025Review
- Heart-on-a-chip systems with tissue-specific functionalities for physiological, pathological, and pharmacological studies.Materials today. Bio · 2024Review
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Cardiotoxicity of cyclophosphamide's metabolites: an in vitro metabolomics approach in AC16 human cardiomyocytes.Archives of toxicology · 2022Article
- Acrolein but not its metabolite, 3-Hydroxypropylmercapturic acid (3HPMA), activates vascular transient receptor potential Ankyrin-1 (TRPA1): Physiological to toxicological implications.Toxicology and applied pharmacology · 2021Article
- Crotonaldehyde-induced vascular relaxation and toxicity: Role of endothelium and transient receptor potential ankyrin-1 (TRPA1).Toxicology and applied pharmacology · 2020Article
- The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2020Review
- Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity.Frontiers in cell and developmental biology · 2020Review
- TRPA1 channel contributes to myocardial ischemia-reperfusion injury.American journal of physiology. Heart and circulatory physiology · 2019Article
- Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system.Biomaterials · 2018Article
- Deficiency of aldose reductase exacerbates early pressure overload-induced cardiac dysfunction and autophagy in mice.Journal of molecular and cellular cardiology · 2018Article
- Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein.Toxicology and applied pharmacology · 2017Article
- Acute cardiopulmonary toxicity of inhaled aldehydes: role of TRPA1.Annals of the New York Academy of Sciences · 2016Review
- Screening and validation for plasma biomarkers of nephrotoxicity based on metabolomics in male rats.Toxicology research · 2016Article
- Ferulic Acid against Cyclophosphamide-Induced Heart Toxicity in Mice by Inhibiting NF-κB Pathway.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.Scientific reports · 2015Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100-300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK · MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein-acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1-5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10-20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity.
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