Genotoxic evaluation of the antimicrobial drug, trimethoprim, in cultured human lymphocytes

Abou-Eisha, Ahmed; Creus, A.; Marcos, Ricard

doi:10.1016/s1383-5718(99)00022-4

Cited by 24 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the genotoxic mechanisms of action of trimethoprim could be related to its capacity to inhibit dihydrofolate reductase. Indeed, the prevention of the reduction of dihydrofolic acid to tetrahydrofolic acid, an essential precursor in the thymidine synthesis pathway, interferes with the DNA synthesis (Abou-Eisha et al, 1999). It has been suggested that oxidative stress could also contribute to genotoxic effects of trimethoprim, because of its capacity to induce electron transport activity of mitochondria, a large source of intracellular ROS under certain conditions (Je zek and Hlavat a, 2005).…”

Section: Discussionmentioning

confidence: 99%

Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

Lacaze

Pédelucq

Fortier

et al. 2015

Environmental Pollution

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

Lacaze

Pédelucq

Fortier

et al. 2015

Environmental Pollution

View full text Add to dashboard Cite

“…In this context, available information pertaining to genotoxic potential of TRIMP is not conclusive. Using a range of bacterial and mammalian systems or assays, both positive and negative responses have been reported in the scientific literature (Stevenson et al 1973;Genther et al 1977;Galloway et al 1998;Rasool et al 1987;Abou-Eisha et al 1999;Abou-Eisha 2006). In addition, despite the fact that genotoxic potency of chemicals is closely tied to their toxicity, which could be determined by different endpoints, there has been very limited information relating to the toxic potential of TRIMP at cellular or sub-cellular levels.…”

Section: Introductionmentioning

confidence: 99%

Relative sensitivity of fish and mammalian cells to the antibiotic, trimethoprim: cytotoxic and genotoxic responses as determined by neutral red retention, Comet and micronucleus assays

2010

View full text Add to dashboard Cite

Relative cytotoxicity and genotoxicity of a widely used antibiotic, trimethoprim (TRIMP) was evaluated under in vitro conditions using rainbow trout gonad-2 (RTG-2) and Chinese hamster ovary-K1 (CHO-K1) cells. Whilst cytotoxicity was determined using neutral red retention (NRR) assay, the genotoxicity was determined using single cell gel electrophoresis or the Comet assay and cytokinesis-block micronucleus (CBMN) assay. For NRR assay, concentration-dependent cytotoxic effect was observed for both the cell lines (estimated EC(50) values: 671.82 ± 21.78 and 611.6 ± 20.4 μg ml(-1) for RTG-2 and CHO-K1 cells, respectively). There was no statistically significant difference between the two cell lines for this assay. For the Comet assay, standard 6 h exposure to TRIMP did not show any positive response for any of the cell types used. However, 48 h exposure to RTG-2 cells showed a concentration-dependent induction of DNA damage (r = 0.86). The highest concentration of TRIMP used (i.e. 100 μg ml(-1)) showed relatively higher DNA damage, compared to ethyl methane sulfonate (EMS; 1 μg ml(-1) or 8 mM), a reference genotoxic agent, used concurrently. In contrast, 24 h exposure time for CHO-K1 cells did not show any concentration-dependent increase for this assay. For MN assay, a significant correlation was found between the MN induction and TRIMP concentration for both the cell lines (RTG-2: r = 0.68; CHO-K1: r = 0.79), although only the highest concentration used showed a significant increase for binucleated (BN) cell with micronuclei (BNMN). The study suggests that whilst the cells of different origin could exhibit similar cytotoxicity, they could display differential genotoxic effects. Furthermore, genotoxic effects of TRIMP are primarily exposure period dependent phenomena and, in addition to inhibiting the action of dihydrofolate reductase, oxidative stress could also contribute for the observed toxic effects, fish cells in general being more sensitive for genotoxic effects.

show abstract

“…clei frequencies were seen after treatment with TMP in human lymphocytes in vitro [Abou-Eisha et al, 1999]. In addition, TMP-induced increases in micronuclei frequencies were observed using the cytokinesis-block micronucleus (CBMN) assay under in vitro conditions in rainbow trout gonads and Chinese hamster ovary cell lines [Papis et al, 2011] was well as in peripheral blood lymphocytes [Abou-Eisha, 2006].…”

Section: Introductionmentioning

confidence: 93%

Trimethoprim-sulfamethoxazole increase micronuclei formation in peripheral blood from weanling well-nourished and malnourished rats

Ortiz

Medina

Cortés

et al. 2011

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is a widely used drug. In spite of this, there are few reports on its genotoxicity, and the results are controversial. Severe malnutrition is a complex condition that increases the susceptibility to infections. Consequently, drugs are extensively used in malnutrition cases. Experimental animal models have been widely used to study the effects of malnutrition. Neonatal rats were experimentally malnourished (UN) during lactation. The UN rats weighed 51.1% less than the well-nourished (WN) controls and had lower concentrations of serum protein and blood lipids. The micronucleus (MN) assay is useful for detecting chromosome damage induced by nutritional deficiencies. In vivo rodent MN assays have been widely used to screen genotoxic agents. In this study, we have evaluated the frequency of spontaneous and TMP-SMX-induced micronuclei in the peripheral blood of weanling (21 days of age) rats using a flow cytometric analysis technique. The spontaneous frequency of micronucleated reticulocytes (MN-RETs) was 2.7 times greater in the UN rats than in the WN rats. In rats that were not treated with TMP-SMX, the percentage of reticulocytes was significantly lower (41.1%) in the UN rats than the WN controls. A therapeutic dose of TMP-SMX (80 mg/kg (TMP), 400 mg/kg (SMX) for 48 hr) increased MN-RETs in the WN and in the UN rats. The data demonstrate the genotoxic effect of this drug. The results indicate that severe protein-calorie restriction and drug treatment enhance DNA damage in rat peripheral blood reticulocytes, potentially increasing the risk of negative effects on health.

show abstract

Genotoxic evaluation of the antimicrobial drug, trimethoprim, in cultured human lymphocytes

Cited by 24 publications

References 30 publications

Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

Relative sensitivity of fish and mammalian cells to the antibiotic, trimethoprim: cytotoxic and genotoxic responses as determined by neutral red retention, Comet and micronucleus assays

Trimethoprim-sulfamethoxazole increase micronuclei formation in peripheral blood from weanling well-nourished and malnourished rats

Contact Info

Product

Resources

About