Synthesis of a palladium(II)-dithiocarbamate complex: biological assay and nephrotoxicity in rats.
A new palladium(II)-dithiocarbamate complex, [Pd(ESDT)Cl](n), was synthesised and its chemical characteristics are discussed. This complex was examined for its cytotoxic properties in human tumour cell lines; for comparison, the cytotoxicity of cisplatin was evaluated under the same experimental conditions. In particular, Pd(II)-complex cytotoxicity on ovarian carcinoma C13 cells, resistant to cisplatin, showed that there seemed to be no cross-resistance between [Pd(ESDT)Cl](n) and cisplatin. The effects on the kidney were also studied. Biochemical investigation on urinary parameters showed that the effects after a single injection are similar to those of cisplatin, with an increase of urinary proteins and enzyme excretion in urine, and a significant decrease of glutamine synthetase activity in the renal tissue. In addition, the Pd(II)-complex caused a significant decrease of p-aminohippuric acid uptake in renal cortical slices relative to cisplatin. On the other hand, histopathological findings showed that the effects of the Pd(II)-complex are more severe and diffuse than the damage caused by cisplatin. Biochemical and histopathological findings show that the Pd(II)-complex affects the pars recta and pars convoluta, in contrast to cisplatin, which only affects the pars recta.
Trevisan
Andrea
A
Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. andrea.trevisan@unipd.it
Marzano
Christine
C
Cristofori
Patrizia
P
Borella Venturini
Matteo
M
Giovagnini
Lorena
L
Fregona
Dolores
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001681:Biological Assay; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D010165:Palladium / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D013859:Thiocarbamates; D010165:Palladium; D002945:Cisplatin