Chloroacetaldehyde : from the implication in the pathophysiological mechanisms of ifosfamide-induced nephrotoxicity to the contribution to its anticancerous effect
type: Dataset
description: Chloroacetaldehyde (CAA), one of the main products of ifosfamide (IFO) hepatic metabolism, is considered as responsible of IFO nephrotoxicity. The mechanisms of this nephrotoxicity are not completely known. In the first part of this study, we tried to clarify the pathophysiological mechanisms of CAA toxicity using precision-cut rat renal cortical slices, then, in the second part, we looked for a possible anticancerous effect of CAA on human breast cancer cells (MCF-7). Using clinically-relevant concentrations (0-75 µM), CAA nephrotoxicity was demonstrated by the depletion of ATP and glutathione and by the inhibition of lactate metabolism. Some of the gluconeogenic enzymes, mainly glyceraldehyde 3-phosphate dehydrogenase, were inhibited by CAA. The complex I of the mitochondrial respiratory chain as well as lactate oxidation were also inhibited by CAA. On the other hand, CAA (10 and 25 µM) inhibited MCF-7 cell proliferation which was not accompanied by cellular ATP depletion. Glucose transport and metabolism as well as some of the glycolytic enzymes were also inhibited by CAA. Hexokinase seems to be the rate-limiting enzyme of glycolysis. In conclusion, CAA is implied in the mechanisms of IFO-induced nephrotoxicity; furthermore, it could, via the inhibition of the glycolytic pathway, contribute to the therapeutic effect of IFO.
landing page: https://theses.hal.science/tel-00697142
identifier: NNT: 2009LYO10209
keyword: cancer
keyword: cell-proliferation
keyword: chloroacetaldehyde
keyword: gluconeogenesis
keyword: glycolyse
keyword: glycolysis
keyword: ifosfamide
keyword: infoeu-reposemanticsdoctoralthesis
keyword: mcf-7
keyword: neoglucogenese
keyword: nephrotoxicite
keyword: nephrotoxicity
keyword: precision-cut-slices
keyword: proliferation-cellulaire
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: theses
keyword: tranches
issued: 2026-05-18T22:51:51.826754
modified: 2026-05-18T22:51:51.826761
language: fr
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Chloroacetaldehyde : from the implication in the pathophysiological mechanisms of ifosfamide-induced nephrotoxicity to the contribution to its anticancerous effect
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00697142
issued: 2026-05-18T22:51:51.877095
modified: 2026-05-18T22:51:51.779927