Possible Interaction: Cisplatin and Glutathione

“BACKGROUND Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin.”

“Conclusions On the basis of our previous experience with the same regimen without GSH, this study suggests that also in the clinical setting, GSH has no negative interference on CDDP activity and that GSH might improve the therapeutic index of CDDP.”

“ GSH is highly expressed in tumor cells and plays a major role in the resistance of tumor cells to cisplatin.”

“One of the chief culprits is the overexpression of glutathione S-transferases (GSTs) in cancer cells, which can accelerate the interaction of glutathione (GSH) with cisplatin , reducing its biological effects.”

“Since the deactivation of cisplatin by glutathione (GSH), is related with the development of cell resistance, the reaction of 1 with GSH was investigated by UV absorption spectroscopy.”

“A close correlation has been drawn between cisplatin resistance in tumor cells and increased levels of intracellular thiol-containing species, especially glutathione (GSH).”

“More importantly, the application of this research tool has unraveled the mechanisms by which the chemoprotective agents sodium thiosulfate, d-methionine, N-acetyl-cysteine and l-glutathione modulate the metabolism of CP in plasma, namely by rapidly reacting with the MHC to form platinum‑sulfur complexes.”

“ Cisplatin treatment significantly increased xanthine oxidase (XO) activity and malondialdehyde (MDA) formation, and significantly decreased the levels and /or activities of enzymatic and non-enzymatic antioxidants ( GSH , GPx, GST, GR, SOD, CAT), in the kidney tissues.”

“Moreover, glutathione (GSH) concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals.”

“It alleviated renal oxidative stress due to cisplatin by lowering lipid peroxides, nitric oxide and Nrf2 levels with concomitant enhancement of GSH and GPx.”