Possible Interaction: Glutathione and Oxaliplatin

“ GSH enhances the reactivity of three anti-cancer drugs (cisplatin, carboplatin and oxaliplatin ) to Cox17, but suppresses the reaction of transplatin.”

“Fragmentation of the collisionally-activated protonated complex of glutathione with oxaliplatin [GSH + OxPt + H](+) resulted in the formation of several species.”

“The results show that at both acute (60 min) and chronic (24 h) durations of incubation, cisplatin and oxaliplatin induced oxidative stress as evidenced by significant inhibition of the activities of SOD, CAT, and GPX enzymes as well as significant reduction of the concentrations of GSH and TAC.”

“Electrospray ionization mass spectrometry (ESI-MS) was applied to detect oxaliplatinGSH adducts formed after incubation of oxaliplatin with GSH.”

“Oxidative stress and inflammation were activated after OXL , and these responses were repressed by MG through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione , decreasing level of nuclear factor of kappa b and downregulating the following pro‐inflammatory cytokines.”

“ Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser)-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala)-expressing cells showed similar whole-cell currents and Ca2+ influx.”

“The results indicated that GSH can interfere with the reaction between oxaliplatin and DNA in two ways.”

“… oxaliplatin … GSH was ∼3.8 × 10–2 M–1 s–1, for cisplatin reacting with GSH ∼2.7 × 10–2 M–1 s–1, and for … ∼1.2 × 10–3 M–1 s–1 (∼32-fold slower than that of oxaliplatin and ∼23-fold slower than that of cisplatin).”

“One such strategy is the "Stop-and-Go" concept, which uses the reversibility of neurologic symptoms to aim at delivering higher cumulative oxaliplatin … is still effective and the other is the administration of neuromodulatory agents (ie, calcium-magnesium infusions, carbamazepine, gabapentin, amifostine, alpha-lipoic acid, and glutathione ) that … oxaliplatin.”