Modulation of Cisplatin Toxicity by Glutathione

Reactivity of a Cytostatic Active N,N-Donor-Containing Dinuclear Pt(II) Complex with Biological Relevant Nucleophiles

“…Furthermore, GSH is used in biological detoxification processes since it is known that complex formation between a heavy metal ion and GSH is the key step in detoxification. − The role of glutathione in the presence of cisplatin was studied in detail. − Glutathione is also present in significant concentrations in cytoplasma and may consequently react with platinum compounds before they can reach the DNA, , or may react with them after they are bound to DNA. − In a clinical phase-I study with cisplatin, it was observed that glutathione can be used as a so-called protecting agent since it interacts readily with the platinum drug and therefore reduces toxicity combined with less negative effects on the antitumor efficiency . The role of glutathione appears to be dual, viz.…”

Why Does Cisplatin Reach Guanine-N7 with Competing S-Donor Ligands Available in the Cell?

“…A special case to be mentioned here is glutathione (GSH); it is present in varying concentrations (0.5−10 mM) in cells and has numerous cellular functions, including the detoxification of chemotherapeutic agents; therefore, it may play a role in modulating cisplatin cell sensitivity. , Recently, GSH was also shown to protect against cisplatin-induced toxicity in animal models. GSH has been administered before cisplatin, but in another study GSH injections were used prior to and after cisplatin . A clinical phase-I study of GSH with cisplatin has shown that toxicity is significantly reduced in the case of ovarian cancer treatment with cisplatin .…”

“…GSH has been administered before cisplatin, 58 but in another study GSH injections were used prior to and after cisplatin. 59 A clinical phase-I study of GSH with cisplatin has shown that toxicity is significantly reduced in the case of ovarian cancer treatment with cisplatin. 60 No significant effects on the antitumor efficiency were observed, but the renal toxicity was significantly reduced.…”

Novel Adducts of the Anticancer Drug Oxaliplatin with Glutathione and Redox Reactions with Glutathione Disulfide

“…[20] Interestingly, however, the strong affinity of sulfur for platinum complexes has led to the coadministration of platinum drugs with glutathione as a chemoprotectant. [21,22] The toxic side-effects are reduced due to reversal or prevention of Pt-S adducts in proteins, while the antitumour activity of cisplatin remains un-affected. [23] Platinum-sulfur adducts might constitute drug reservoirs from which the platinum could later be transferred onto the target DNA.…”