Genotoxicity and cell death induced by tinidazole (TNZ).

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Lopez Nigro MM, Carballo MA

Genotoxicity and cell death induced by tinidazole (TNZ).

Toxicol Lett. 2008 Jul 30;180(1):46-52. doi: 10.1016/j.toxlet.2008.05.017. Epub 2008 Jun 5.

PubMed ID

18582545 [ View in PubMed

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Abstract

Tinidazole (TNZ), a second-generation 5-nitroimidazole compound chemically related to metronidazole (MTZ), has been widely used throughout Europe and developing countries for the treatment of amoebic and parasitic infections. Despite TNZ's increasing use in therapeutics, scarce experimental reports are available in literature on its potential genotoxicity in human cells. Therefore, the aim of the present study was to achieve a precise characterization of the cytotoxic and genotoxic activities of this nitroimidazole in cultured human lymphocytes at therapeutic concentrations (0.1, 1, 10 and 50 microg/ml of culture) and evaluate the possible cell death mechanism associated with it. The endpoints analyzed included: mitotic index (MI), replication index (RI), sister chromatid exchange (SCE) and chromosomal aberrations (CA). A significant decrease (p<0.0001) in MI as well as an increase in SCE (p<0.0001) and CA (p<0.0001) frequencies were observed. No modifications in RI were found. The results suggest a genotoxic and cytotoxic effect of TNZ related with cell death process. Therefore, we evaluated this mechanism by DNA fragmentation (laddering), fluorescence microscopy using acridine orange/ethidium bromide (AO/EB) staining and flow cytometry propidium iodide (PI). DNA extracts of TNZ-treated cells resulted in nucleosomal DNA ladder pattern after 48 h of cell treatment; meanwhile no differences were detected in untreated cells. This pattern correlated with the observed decrease in cellular viability (p<0.05), morphological evidence of apoptosis and increase in the percentage of nuclei with hypodiploid DNA content of TNZ exposed cultures compared with control (p<0.05). We concluded that TNZ is genotoxic, cytotoxic and is able to modulate cell death through apoptotic mechanisms in the experimental design employed.

DrugBank Data that Cites this Article

Drugs

Tinidazole

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tinidazole	DNA	Nucleotide	Humans	Yes	Binder	Details