Cisplatin-induced renal toxicity and toxicity-modulating strategies: a review

What do we know about the reduction of Pt(IV) pro-drugs?

“…The Pt(III) could react rapidly with another [Cr(bipy) 3 ] 2+ to yield Pt(II) but other reactions were possible. When the Pt(IV) complex had a chloride ligand such as [Pt(NH 3 ) 5 Cl] 3+ , the data supported an inner sphere mechanism where the chloride was serving as a bridging group. They also suggested a two electron reduction to yield Pt(II) and Cr(IV) complexes with the latter being subsequently reduced by Cr(II).…”

“…Cisplatin is one of the most successful anticancer drugs, being especially effective against testicular cancer where it attains a cure rate of 90%. Like most cytotoxic agents, it causes severe side-effects, including nephrotoxicity, neurotoxicity, ototoxicity, nausea and vomiting which limit the dose that can be administered to patients [5]. Among the many analogs of cisplatin that were synthesized, the second generation drug, carboplatin has considerably less adverse side effects than cisplatin, making possible high-dose chemotherapy.…”

A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin

“…Here, we investigated whether Δ-Ru1 causes kidney damage. Serum creatinine is usually used to evaluate the glomerular filtration rate and to determine the impairment of renal function [37]. In this study, the animals treated with cisplatin presented a high plasmatic level of creatinine (Fig.…”

Alteration of Pharmacokinetics and Nephrotoxicity of Cisplatin by Alginates

“…Nucleophilic thiol reagents have a potential for reacting with and inactivating toxic cisplatin metabolites, their action being based on the affinity of sulfur-containing ligands for platinum-(II) complexes. 8,9 However, these chemoprotectors also have major problems, such as intrinsic toxicity, lack of selectivity, and reduction of antitumor activity. Sodium thiosulfate reduces not only the nephrotoxicity of cisplatin, but also its antitumor activity by reacting chemically with it, forming a soluble, biologically inactive product.…”