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Evidence that fodip...
Evidence that fodipir (DPDP) binds neurotoxic Pt2+ with a high affinity : An electron paramagnetic resonance study
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- Stehr, Jan Eric, 1981- (författare)
- Linköpings universitet,Ytors Fysik och Kemi,Biomolekylär och Organisk Elektronik,Tekniska fakulteten
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- Lundström, Ingemar, 1941- (författare)
- Linköpings universitet,Sensor- och aktuatorsystem,Tekniska fakulteten
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- Karlsson, Jan Olof G., 1951- (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten
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(creator_code:org_t)
- 2019-11-01
- 2019
- Engelska.
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
- Relaterad länk:
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https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Oxaliplatin typically causes acute neuropathic problems, which may, in a dose-dependent manner, develop into a chronic form of chemotherapy-induced peripheral neuropathy (CIPN), which is associated with retention of Pt2+ in the dorsal root ganglion. A clinical study by Coriat and co-workers suggests that co-treatment with mangafodipir [Manganese(II) DiPyridoxyl DiPhosphate; MnDPDP] cures ongoing CIPN. These authors anticipated that it is the manganese superoxide dismutase mimetic activity of MnDPDP that explains its curative activity. However, this is questionable from a pharmacokinetic perspective. Another, but until recently undisclosed possibility is that Pt2+ outcompetes Mn2+/Ca2+/Zn2+ for binding to DPDP or its dephosphorylated metabolite PLED (diPyridoxyL EthylDiamine) and transforms toxic Pt2+ into a non-toxic complex, which can be readily excreted from the body. We have used electron paramagnetic resonance guided competition experiments between MnDPDP (10logKML ≈ 15) and K2PtCl4, and between MnDPDP and ZnCl2 (10logKML ≈ 19), respectively, in order to obtain an estimate the 10logKML of PtDPDP. Optical absorption spectroscopy revealed a unique absorption line at 255 nm for PtDPDP. The experimental data suggest that PtDPDP has a higher formation constant than that of ZnDPDP, i.e., higher than 19. The present results suggest that DPDP/PLED has a high enough affinity for Pt2+ acting as an efficacious drug in chronic Pt2+-associated CIPN.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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