ArticleThe Journal of pharmacology and experimental therapeutics2009
Increased sensitivity of glutathione S-transferase P-null mice to cyclophosphamide-induced urinary bladder toxicity.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- A Rare Case of P-Null Phenotype Identified During Preoperative Screening.Clinical case reports · 2026Article
- Mitigating cyclophosphamide-induced hepatorenal toxicity: Linalool's role in modulating oxidative stress, inflammation, and apoptosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction.Physiological reports · 2021Article
- Glutathione S-transferase P deficiency induces glucose intolerance via JNK-dependent enhancement of hepatic gluconeogenesis.American journal of physiology. Endocrinology and metabolism · 2018Article
- Electronic cigarette-generated aldehydes: The contribution of e-liquid components to their formation and the use of urinary aldehyde metabolites as biomarkers of exposure.Aerosol science and technology : the journal of the American Association for Aerosol Research · 2018Article
- GSTA1 diplotypes affect busulfan clearance and toxicity in children undergoing allogeneic hematopoietic stem cell transplantation: a multicenter study.Oncotarget · 2017Article
- 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
- TRPA1: Acrolein meets its target.Toxicology and applied pharmacology · 2017Article
- The Association of CombinedFrontiers in pharmacology · 2017Article
- Article
- Attenuation of lung fibrosis in mice with a clinically relevant inhibitor of glutathione-JCI insight · 2016Article
- RETRACTED: Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice.PloS one · 2016Article
- Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.Scientific reports · 2015Article
- Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.Circulation research · 2015Article
- Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice.Toxicology and applied pharmacology · 2015Article
- Inflammation and pyroptosis mediate muscle expansion in an interleukin-1β (IL-1β)-dependent manner.The Journal of biological chemistry · 2015Article
- Article
- Acrolein exposure is associated with increased cardiovascular disease risk.Journal of the American Heart Association · 2014Article
- Mice lacking three Loci encoding 14 glutathione transferase genes: a novel tool for assigning function to the GSTP, GSTM, and GSTT families.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hemorrhagic cystitis and diffuse inflammation of the bladder, common side effects of cyclophosphamide (CY) treatment, have been linked to the generation of acrolein derived from CY metabolism. Metabolic removal of acrolein involves multiple pathways, which include reduction, oxidation, and conjugation with glutathione. Herein, we tested the hypothesis that glutathione S-transferase P (GSTP), the GST isoform that displays high catalytic efficiency with acrolein, protects against CY-induced urotoxicity by detoxifying acrolein. Treatment of wild-type (WT) and mGstP1/P2 null (GSTP-null) mice with CY caused hemorrhagic cystitis, edema, albumin extravasation, and sloughing of bladder epithelium; however, CY-induced bladder ulcerations of the lamina propria were more numerous and more severe in GSTP-null mice. CY treatment also led to greater accumulation of myeloperoxidase-positive cells and specific protein-acrolein adducts in the bladder of GSTP-null than WT mice. There was no difference in hepatic microsomal production of acrolein from CY or urinary hydroxypropyl mercapturic acid output between WT and GSTP-null mice, but CY induced greater c-Jun NH(2)-terminal kinase (JNK) and c-Jun, but not extracellular signal-regulated kinase or p38, activation in GSTP-null than in WT mice. Pretreatment with mesna (2-mercaptoethane sulfonate sodium) abolished CY toxicity and JNK activation in GSTP-null mice. Taken together, these data support the view that GSTP prevents CY-induced bladder toxicity, in part by detoxifying acrolein. Because polymorphisms in human GSTP gene code for protein variants differing significantly in their catalytic efficiency toward acrolein, it is likely that GSTP polymorphisms influence CY urotoxicity. In addition, pretreatment with dietary or nutrient inducers of GSTP may be of use in minimizing bladder injury in patients undergoing CY therapy.
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