In vitro toxicological evaluation of a dinuclear platinum(II) complex with acetate ligands.
In the present study the toxicological potential of a tumor-inhibiting dinuclear platinum(II) complex (bis(acetato)diammine-bis-micro-acetato diplatinum(II) dihydrate (BAP)) was evaluated, utilizing in vitro models of nephrotoxicity, myelosuppression and neurotoxicity. Regarding the discrepancies between the hallmark toxicity of the clinically utilized platinum drugs, we used three distinct referent compounds as follows cisplatin for the assessment of in vitro nephrotoxicity, carboplatin in case of cultured bone marrow cells and oxaliplatin for the determination of the in vitro neurotoxicty, respectively. The results obtained indicate that the investigated dinuclear complex is endowed by a lower potential to induce detrimental effects upon these typically susceptible platinum toxicity cellular populations as compared to the corresponding referent drugs. These findings, together with the previously encountered profound cytotoxic efficiency of this dinuclear platinum(II) complex against human tumor cell lines, recall for a further detailed evaluation of BAP as potential antineoplastic agent.
Laboratory of Molecular Pharmacology and Experimental Chemotherapy, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria. gmomekov@satline.net
Georgi
G
Momekov
Dilyan
D
Ferdinandov
Adriana
A
Bakalova
Maya
M
Zaharieva
Spiro
S
Konstantinov
Margarita
M
Karaivanova
D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D016190:Carboplatin / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002678:Chimera; D002945:Cisplatin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D051381:Rats
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C519466:bis(acetato)diammine-bis-micro-acetato diplatinum (II) dihydrate; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin