Abstract
In previous papers, we have reported on the high antifungal and significant antibacterial activity against Gram-positive and Gram-negative bacteria of the water-soluble silver(I) complexes of metronidazole and derivatives of pyridine compared to silver nitrate. In the present study, the cytotoxic activity of the silver(I) complexes of metronidazole and 4-hydroxymethylpyridine was compared with that of silver nitrate. Metronidazole and 4-hydroxymethylpyridine were investigated using Balb/c 3T3 and HepG2 cell lines in order to evaluate the potential clinical application of silver(I) complexes. The cells were exposed for 72 h to compounds at eight concentrations. The cytotoxic concentrations (IC50) of the study compounds were assessed within four biochemical endpoints: mitochondrial activity, lysosomal activity, cellular membrane integrity, and total protein content. The investigated silver(I) complexes displayed comparable cytotoxicity to that of silver nitrate used in clinics. Mean cytotoxic concentrations calculated for investigated silver(I) complexes from concentration–response curves ranged from 2.13 to 26.5 µM. HepG2 cells were less sensitive to the tested complexes compared to fibroblasts (Balb/c 3T3). However, the most affected endpoint for HepG2 cells was cellular membrane damage. The cytotoxicity of both silver complexes was comparable for Balb/c 3T3 cells. The cytotoxic potential of the new silver(I) compounds compared to that of silver nitrate used in medicine indicates that they are safe and could be used in clinical practice. The presented results are yet more stimulating to further studies that evaluate the therapeutic use of silver complexes.
Highlights
Research efforts targeting the development of new chemotherapeutic agents play an important role in medicine
The cytotoxicity was assessed against the non-metabolized cell line, Balb/c 3T3, and the metabolized cell line, HepG2
The tested silver(I) complexes displayed comparable toxicity with AgNO3 in both cell lines. Their antibacterial potency was higher than that of AgNO3, a drug which is used in clinical practices as shown in previous studies
Summary
Research efforts targeting the development of new chemotherapeutic agents play an important role in medicine. High hopes of researchers are associated with silver ions. Silver has been used since ancient times for the purpose of wound healing and is a known antimicrobial agent that exhibits increased antimicrobial action. When silver comes in contact with microorganisms, there is immediate distortion of the cell wall, which later leads to the death of these organisms. Silver was proved to influence the metabolic behavior of bacteria, viruses, and eukaryotic microorganisms. It has been suggested that silver(I) ions modify their pathogenic activity through interaction with microbial electron transport
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