Kidney injury is an important side effect of the chemotherapeutic agent ifosfamide in humans. Previous studies have shown that treatment with ifosfamide reduces kidney glutathione and that the toxicity of ifosfamide is enhanced in glutathione-depleted renal tubule cells in vitro. In this study, we examined the effect of glutathione depletion on ifosfamide nephrotoxicity in vivo using rats treated with the glutathione-depleting agent buthionine sulfoximine. Animals received 80 mg/kg ifosfamide intraperitoneally daily for three days with or without buthionine sulfoximine in drinking water. Buthionine sulfoximine produced a significant fall in renal glutathione content but did not affect kidney function. Ifosfamide-treated rats developed low-grade glucosuria, phosphaturia and proteinuria that worsened with concomitant buthionine sulfoximine therapy. These findings indicate that glutathione depletion exacerbates ifosfamide nephrotoxicity in rats and suggest that pharmacological methods for replenishing intracellular glutathione may be effective in ameliorating ifosfamide-induced renal injury.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614706 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Cotargeting of thioredoxin 1 and glutamate-cysteine ligase in both imatinib-sensitive and imatinib-resistant CML cells.
Biochem Pharmacol
January 2025
Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, RP China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China. Electronic address:
Chronic myeloid leukemia (CML) is a type of malignancy characterized by harboring the oncogene Bcr-Abl, which encodes the constitutively activated tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors targeting BCR-ABL have revolutionized CML therapy, native and acquired drug resistance commonly remains a great challenge. Thioredoxin 1 (Trx1) and glutamate-cysteine ligase (GCL), which are two major antioxidants that maintain cellular redox homeostasis, are potential targets for cancer therapy and overcoming drug resistance.
View Article and Find Full Text PDF"Effects of Redox Status on Immediate Hypericin-Mediated Photodynamic Therapy in Human Glioblastoma T98G Cell Line".
ACS Omega
January 2025
Departament of Physiological Sciences, State University of Maringa, Maringa, Parana 87020-900, Brazil.
Glioblastoma Multiforme (GBM) is one of the most aggressive types of brain tumor. GBM can modulate glutathione (GSH) levels and regulate cellular redox state, which can explain its high resistance to chemotherapeutic agents. Photodynamic therapy (PDT) is a selective, nontoxic, and minimally invasive treatment approved for many types of cancer.
View Article and Find Full Text PDFButhionine sulfoximine acts synergistically with doxorubicin as a sensitizer molecule on different tumor cell lines.
J Toxicol Environ Health A
January 2025
Laboratory of Experimental Cancerology (LabCancer), Department of Biophysics and Physiology, Federal University of Piauí, Teresina-PI, Brazil.
The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines.
View Article and Find Full Text PDFBiodegradable copper-doped calcium phosphate nanoplatform enables tumor microenvironment modulations for amplified ferroptosis in cervical carcinoma treatment.
Int J Pharm X
June 2025
Department of Gynecology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, PR China.
As a recently discovered form of regulated cell death, ferroptosis has attracted much attention in the field cancer therapy. However, achieving considerably enhanced efficacy is often restricted by the overexpression of endogenous glutathione (GSH) in tumor microenvironment (TME). In this work, we report a ferroptosis-inducing strategy of GSH depletion and reactive oxygen species (ROS) generation based on a biodegradable copper-doped calcium phosphate (CaP) with L-buthionine sulfoximine (BSO) loading (denoted as BSO@CuCaP-LOD, BCCL).
View Article and Find Full Text PDFDLBCL cells with ferroptosis morphology can be detected with a deep convolutional neural network.
Biomed Pharmacother
January 2025
Medical Research Center, Oulu University Hospital, Oulu, Finland; Department of Internal Medicine, Länsi-Pohja Central Hospital, Kemi, Finland; Biomedicine and Internal Medicine Research Unit, University of Oulu, Oulu, Finland.
It has been demonstrated that diffuse large B-cell lymphoma (DLBCL) is especially sensitive to ferroptosis. Currently, confirming the presence of ferroptosis requires flow cytometry, which is a time consuming and labor-intensive task. Blistering of the cell membrane has been shown to be a ferroptosis-specific morphological change.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!