Antiglioma activity of 2,2′:6′,2ʺ-terpyridineplatinum(II) complexes in a rat model—Effects on cellular redox metabolism

摘要: Abstract The mammalian thioredoxin system, comprising the selenoenzyme reductase (TrxR) and 12-kDa protein (Trx), is implicated in thiol-mediated antioxidant defense redox regulatory processes including transcriptional control, DNA synthesis, apoptosis. Cell proliferation supported by system can be suppressed TrxR inhibition. In this study, we assessed effects of potent hTrxR inhibitors 4-mercaptopyridine (4′-chloro-2,2′:6′,2ʺ-terpyridine)platinum nitrate (I232N) 2-mercaptopyridine (I252N) on glioblastoma a rat model. These compounds show no or little cross-resistance with cisplatin are thus great clinical interest. Triple intravenous application 25–35 mg/kg led to significant decrease tumor growth as determined magnetic resonance imaging. Metabolic well parameters blood animals were not altered. However, activity was significantly decreased tissue, parameters—including glutathione concentrations, total status, activities different enzymes—showed tissue-specific variations. As indicated apoptotic markers, antitumor I232N mediated induction programmed cell death but rather inhibition intercalation leading cycle arrest.