DNA single strand breaks in peripheral blood lymphocytes induced by three nitroimidazole derivatives

Ferreiro, Gisell Rodriguez; Badı́as, Lourdes Cancino; López-Nigro, Marcela; Palermo, Ana María; Mudry, Marta Dolores; Elio, Prieto González; Carballo, Marta A.

doi:10.1016/s0378-4274(02)00039-5

Cited by 63 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All of these drugs cause serious in vivo side effects, often in the gastrointestinal tract, which frequently necessitate treatment interruption (9). In vitro genotoxic and cytotoxic effects of nitroimidazoles have been shown as well (20,29). Moreover, the development of resistance has been demonstrated both in vitro and in vivo (for comprehensive reviews, see references 3 and 36).…”

mentioning

confidence: 99%

A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia

Sonda

Štefanić

Hehl

2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Sphingolipid biosynthesis pathways have recently emerged as a promising target for therapeutic intervention against pathogens, including parasites. A key step in the synthesis of complex sphingolipids is the glucosylation of ceramide, mediated by glucosylceramide (GlcCer) synthase, whose activity can be inhibited by PPMP (1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). In this study, we investigated whether PPMP inhibits the proliferation and differentiation of the pathogenic parasite Giardia lamblia, the major cause of parasiteinduced diarrhea worldwide. PPMP was found to block in vitro parasite replication in a dose-dependent manner, with a 50% inhibitory concentration of 3.5 M. The inhibition of parasite replication was irreversible at 10 M PPMP, a concentration that did not affect mammalian cell metabolism. Importantly, PPMP inhibited the completion of cell division at a specific stage in late cytokinesis. Microscopic analysis of cells incubated with PPMP revealed the aberrant accumulation of cellular membranes belonging to the endoplasmic reticulum network in the caudal area of the parasites. Finally, PPMP induced a 90% reduction in G. lamblia differentiation into cysts, the parasite stage responsible for the transmission of the disease. These results show that PPMP is a powerful inhibitor of G. lamblia in vitro and that as-yet-uncharacterized sphingolipid biosynthetic pathways are potential targets for the development of anti-G. lamblia agents.

show abstract

mentioning

confidence: 99%

A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia

Sonda

Štefanić

Hehl

2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…It has been reported that MTZ induced single-strand DNA breaks and produced DNA fragmentation and unscheduled DNA synthesis in primary cultures of both rat and human hepatocytes (Martelli et al, 1990;Reitz et al, 1991;Menendez et al, 2001;Tocher and Edwards, 1994). Rodriguez et al reported that ONZ caused DNA single-strand breaks at 10-, 100-, and 500-μg/mL concentrations (Rodriguez et al, 2002). Oxidative metabolites of MTZ, rather than by the parent compound itself, have been claimed to be responsible for DNA-break formation.…”

Section: Discussionmentioning

confidence: 99%

The evaluation of genotoxic potential of ornidazole, nitroimidazole, in lymphocyte culture of patients with amebiasis

İkbal

Yılmaz

Doğan

et al. 2011

Drug and Chemical Toxicology

View full text Add to dashboard Cite

The genotoxicity study of ornidazole (ONZ) was carried out on human lymphocyte chromosomes, using sister chromatid exchange (SCE) and micronucleus (MN). Thirty-two patients with Entemoeba histolitica infection who received 1000 mg/day for 10 days were included in this study. SCE and MN were measured before and after therapy. A statistically significant increase was observed in the SCE (P < 0.001) and MN frequencies (P < 0.001) after ornidazole therapy. It was concluded that ONZ has a potential geno- and cytotoxic effect in human peripheral lymphocyte cultures. For this reason, further, detailed studies are needed to elucidate the ONZ mechanism of genotoxicity and its carcinogenic potential.

show abstract

“…The evaluation of DNA damage was carried out as described by Rodriguez‐Ferreiro et al. (2002) with a slight modification.…”

Section: Methodsmentioning

confidence: 99%

Antigenotoxic, Fibrinolytic and Immunomodulating Activity of Traditionally Fermented Soy Product, Chungkukjang

Kim¹,

Heo

Wang

2009

Journal of Food Processing and Preservation

View full text Add to dashboard Cite

Fibrinolytic, antigenotoxic and immunomodulating properties of chungkukjang were evaluated. The purified fibrinolytic enzyme was characterized as an alkaline serine protease with molecular weight of 22 kDa determined by fibrin zymography and stable over pH range 6.0–10.0 below 50C. The comet assay showed that N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced DNA damage level (190.8 AU) in 3T3 cells was considerably decreased to 121.2 AU with chungkukjang extracts (CB) showing 49.7% of protection. Incubation of the 3T3 cells with CB significantly reduced the cytotoxicity of MNNG. [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] (MTT) assay revealed that the addition of CB enhanced the proliferation of RAW 264.7 (mouse leukemic monocyte macrophage cell line) macrophages up to about 150% of the control levels. RAW 264.7 macrophages incubated with CB induced a strong increase in nitric oxide (NO), tumor necrosis factor‐α (TNF‐α) and interleukin‐1α (IL‐1α) with a dose‐dependent manner. After 24 h incubation with 1 mg/mL of CB, NO, TNF‐α and IL‐1α showed the highest production of 511, 2.46 and 0.258 ng/mL, respectively.

show abstract

DNA single strand breaks in peripheral blood lymphocytes induced by three nitroimidazole derivatives

Cited by 63 publications

References 37 publications

A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia

A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia

The evaluation of genotoxic potential of ornidazole, nitroimidazole, in lymphocyte culture of patients with amebiasis

Antigenotoxic, Fibrinolytic and Immunomodulating Activity of Traditionally Fermented Soy Product, Chungkukjang

Contact Info

Product

Resources

About