A multi-biomarker assessment of the impact of the antibacterial trimethoprim on the non-target organism Zebra mussel (Dreissena polymorpha)

Binelli, Andrea; Parolini, Marco; Cogni, D.; Pedriali, Alessandra; Provini, A.

doi:10.1016/j.cbpc.2009.05.011

Cited by 28 publications

(24 citation statements)

References 42 publications

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“…The enhancement of ROS formation will result in oxidative stress when the balance between the pro-oxidant mechanisms and antioxidant defences is overcome (Winston and Di Giulio 1991). Many authors have reported good correlations between lysosomal membrane destabilisation and the impairment of the antioxidant defence system in different biological models, including mussels (Winston et al 1996;Mamaca et al 2005;Binelli et al 2009b), and others have suggested that reactive free radicals contribute to the destabilisation of lysosomal membranes (Winston et al 1996). Accordingly, our data showed an overall significant (P \ 0.05) correlation between the NRRT and the activity of detoxifying (GST) and antioxidant (SOD, CAT and .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the difference in enzymatic responses could be explained by the variability of the dissimilar enzyme activities that are involved in a wide and complex system that regulates of homeostasis, which is usually not able to counterbalance completely the overproduction of ROS (Valavanidis et al 2006). Several studies have demonstrated the high variability of antioxidant responses, showing notable differences among species, tissues, pollutants and exposure concentrations (Regoli et al 2003;Osman and van Noort 2007;Binelli et al 2009b). However, the significant correlation between all of the antioxidant enzyme activities, mainly under the High treatment, suggests the activation of the entire defence pathway against ROS in zebra mussels (Table 2).…”

Section: Discussionmentioning

confidence: 99%

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Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha

Parolini

Binelli

2011

Ecotoxicology

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Non-steroidal anti-inflammatory drugs (NSAIDs) are the sixth top-selling drugs worldwide and are commonly found in freshwater ecosystems in the high ng/l to low μg/l range. Recent studies have investigated both the acute and the chronic toxicity of single NSAIDs on different biological models, but these studies have completely neglected the fact that, in the environment, non-target organisms are exposed to mixtures of drugs that have unforeseeable toxicological behavior. This work investigated the sub-lethal effects induced by a mixture of three common NSAIDs, namely, diclofenac, ibuprofen and paracetamol, on the freshwater bivalve, the zebra mussel (Dreissena polymorpha). The mussels were exposed to three different environmental concentrations of the mixture (Low, Mid and High). A multi-biomarker approach was used to highlight cyto-genotoxic effects and the imbalance of the oxidative status of the treated specimens. The Neutral Red Retention Assay (NRRA) was used as a biomarker of cytotoxicity, whereas the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase were measured to assess the role played by the oxidative stress enzymes. In addition, the single cell gel electrophoresis assay, the DNA Diffusion assay and the micronucleus test were used to investigate possible genotoxic effects. According to our NRRA results, each treatment was able to induce a significant cellular stress in bivalves, probably due to the raise of oxidative stress, as indicated by the alteration of enzyme activities measured in treated specimens. Moreover, the mixture induced significant enhancements of DNA fragmentation, which preluded fixed genetic damage, as highlighted by the increase of both apoptotic and micronucleated cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha

Parolini

Binelli

2011

Ecotoxicology

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“…Subsequent, in vivo techniques using a range of biological responses or biomarkers following 96 h exposure of fresh water mussels, Dreissena polymorpha have also indicated a slight increase for DNA damage (i.e. MN and Comet assays, apoptosis induction) but a significant damage for the lysosomal membrane integrity using NRR assay (Binelli et al 2009b).…”

Section: Discussionmentioning

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

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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.

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“…Researchers are concerned about the implications of pharmaceuticals and have emphasized the necessity of long term and life cycle exposure studies of pharmaceuticals on non-target organisms (Daughton and Ternes 1999;Boxall et al 2003b). Despite antibiotics being designed to work against target-sites, unexpected effects, such as cytotoxicity and genotoxicity, on non-target organisms (Binelli et al 2009) and multidrug resistance caused by the production of reactive oxygen species (ROS) have been reported (Kohanski et al 2007;Kohanski et al 2010). Therefore, the long-term ecotoxicological effects of antibiotics, especially mutigenerational effects, are essential, but few studies have been reported on aquatic organisms.…”

Section: Introductionmentioning

confidence: 99%

The individual and population effects of tetracycline on Daphnia magna in multigenerational exposure

Kim

Lee

et al. 2012

Ecotoxicology

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Multigenerational exposure of Daphnia magna to tetracycline was carried out through four consecutive generations. The effects of tetracycline on the survival, reproduction and growth of D. magna were assessed over a period of 21 days per generation. The evaluated endpoints were overall fecundity (total mean neonates per female over 21 days), time to first reproduction, longevity, molting number and somatic growth, such as body weight and body length. Using the results obtained for reproduction and survival rates, the intrinsic population growth rate (PGR) was calculated and compared throughout the generations. Reproductive impairment was observed in all generations and magnified with increasing generation number. The value of no observed effect concentration on D. magna also markedly decreased with increasing generation number. This subsequently resulted in a reduction of the PGR value. In addition, the PGR value was decreased with increasing exposure concentration, decreasing by about 30 and 60% at 0.1 and 5.0 mg/L tetracycline, respectively. On the other hands, somatic growth increased with increasing generation number, because the remaining input energy from the reduced reproduction was mainly used for body maintenance. As a result, the somatic growth and reproduction showed reversed trends on continuous exposure of tetracycline to four generations. In conclusion, multigenerational exposure of tetracycline can induce overall responses on reproduction and the somatic growth of D. magna. Moreover, the PGR value of D. magna exposed to tetracycline was reduced with increasing generation number; thereby, inhibiting the long term propagation of D. magna.

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A multi-biomarker assessment of the impact of the antibacterial trimethoprim on the non-target organism Zebra mussel (Dreissena polymorpha)

Cited by 28 publications

References 42 publications

Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha

Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha

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

The individual and population effects of tetracycline on Daphnia magna in multigenerational exposure

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