In vitro toxicological evaluation of a dinuclear platinum(II) complex with acetate ligands

Abstract

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.

Cellular Pharmacology, Antineoplastic Activity and Low In Vivo Toxicity of a Carboxylato-Bridged Platinum(II) Complex bis(acetato)diammine-bis-μ-acetato diplatinum (II) Dihydrate

“…Additional shortcoming of the second generation platinum drugs is their dose-limiting myelotoxicity in contrast to cisplatin, which has only moderate myelosuppressive potential [1]. In a dissimilar fashion in BAP the encountered low nephrotoxicity is accompanied with low myelosuppression, while attaining profound cytotoxic/antineoplastic efficacy in line with our previously described paper addressing the in vitro toxicological potential of BAP upon cultured proximal tubule epithelium, neurones and bone marrow cells [12].…”

“…More recently the former complex -bis(acetato)diammine-bis-μ-acetato diplatinum (II) dihydrate (BAP (1)), was found to significantly outclass the remaining analogues in a spectrum of human and animal tumor cell lines whereby its activity was equalto-superior relative to cisplatin [10,11]. Furthermore this complex has demonstrated quite less pronounced propensity to induce detrimental effects upon cellular populations susceptible to platinum toxicity -renal epithelium, primary neurons and long term bone marrow cell cultures as compared to the clinically applied platinum drugs cisplatin, carboplatin and oxaliplatin [12].…”

Pharmacological effects of asiatic acid in glioblastoma cells under hypoxia

“…Cisplatin enters cells by passive diffusion and produces its cytotoxicity via DNA intercalation inducing apoptosis and changes in cell cycle [6, 20–23]. However, cisplatin efficacy is reduced under hypoxia [24], and its unfavorable toxicological profile characterized by nephrotoxicity, neurotoxicity, nausea, vomiting, and immunosuppression limit its clinical usefulness [6, 25]. Additionally, the absorption of cisplatin into the perifocal tumor is hindered by the presence of the BBB [26].…”

The effects of cysplatin on human adipose tissue derived mesenchymal stromal cells under different oxygen levels

“…Цисплатин (CPt) (цис-диамин-дихлор-платина) -один из самых мощных химиотерапевтиче-ских агентов, используемых против широкого спектра злокачественных опухолей, в том числе головы и шеи, семенников, яичников, мочевого пузыря и легких [4]. Тем не менее его положительные эффекты ограничены из-за токсического действия на нетрансформированные здоровые ткани организма [5]. Исследования показали, что в ответ на химиотерапию ММСК костного мозга мигрируют из своей ниши, по-видимому, с целью под-держки регенерации тканей [6].…”