The use of 1H spin echo NMR and HPLC to confirm doxorubicin induced depletion of glutathione in the intact HeLa cell.
The effects of doxorubicin on the cellular biochemistry of the HeLa cell using 1H spin echo nuclear magnetic resonance spectroscopy (NMR) of the intact and viable cell in conjunction with dual wavelength HPLC of cell lysates is reported. Directly dose-related changes were observed in lactate and reduced glutathione concentration. Doxorubicin induces a time-dependent depletion of the cytosolic pool of glutathione and a change in the glycolytic pattern of the cell. The glutathione depletion could be partially reversed by controlled pre-treatment of the cells with N-acetylcysteine and cysteine, the protection being linked to the intracellular concentration of the thiol.
al-Kabban
M
M
Department of Pathological Biochemistry, Glasgow Royal Infirmary, UK.
Watson
I D
ID
Stewart
M J
MJ
Reglinski
J
J
Smith
W E
WE
Suckling
C J
CJ
D000111:Acetylcysteine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy
D007773:Lactates; D004317:Doxorubicin; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine