Possible Interaction: Glutathione and Platinum

“Results showed … high GSH levels may be involved, … least partially, in determining platinum drug resistance in vivo in at least some of the tumour models studied (ADJ/PC6 carboplatin and tetraplatin … tumours; L1210 cisplatin and tetraplatin resistant tumours and the HX/62 and OVCAR-3 human ovarian carcinoma xenografts).”

“Cellular sensitivity to platinum is increased when glutathione levels are reduced, just as is radiosensitivity.”

“In conclusion, the results of this study illustrate that STS, GSH , and AC affect Pt binding in whole blood, which suggests that these compounds could affect Pt binding in patients.”

“ GSH may have modulated the cytotoxicity of these platinum complexes by other means such as effects on DNA repair, apoptosis, free radical scavenging or through other yet unidentified mechanisms.”

“ Glutathione (GSH) may be one of the factors responsible for this phenomenon as it counteracts the cytotoxic effects of platinum containing drugs and radiation.”

“It has been suggested that GSH may reduce the cytotoxicity of these drugs by forming inactive conjugates and by enhancing the repair of DNA‐platinum crosslinks.”

“It appeared that GSH protects bacteria at least by covalently trapping platinum before its binding to DNA since (i) lower binding of CDDP to DNA was found when GSH was present and (ii) the resistance still persisted in bacteria after treatment by the monofunctional derivative [Pt(dien)Cl]Cl.”

“The relative importance of these two mechanisms of detoxification is unknown, although both mechanisms probably contribute to glutathione modulation of platinum toxicity.”