Preliminary investigation of multi-biomarker responses in three-spined stickleback (Gasterosteus aculeatus L.) sampled in contaminated streams

International audienceRecently, the three-spined stickleback (Gasterosteus aculeatus L.) has been proposed as a suitable fish species for detecting both androgen- and estrogen-induced endocrine disruption by environmental pollutants. This relatively pollution-tolerant fish is present in most European streams and small rivers but also coastal and estuarian areas. The purpose of the present field study was to determine the extent to which multiple biomarkers in this fish species could distinguish between streams with different pollution levels. Sticklebacks were sampled in French rivers characterised by various urban, industrial or agricultural contaminations and in outdoor lotic mesocosms as reference site. Physiological parameters including condition factor and liver somatic index, biotransformation enzymes such as 7-ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase, antioxidant enzymes including glutathione peroxidase and total glutathione (GSH) content and lipoperoxidation (as TBARS) showed several differences between sites. For example, fish from an heavily contaminated stream exhibited a 9-fold EROD induction associated to a decrease of GSH and a 3-fold increase of TBARS content in comparison to fish from uncontaminated sites. When fish were transferred from polluted river to clean water, some of these biomarkers rapidly returned to basal levels found in fish in the reference site while others, like TBARS levels were still high after 2 weeks of depuration. Based on multivariate analyses, the battery of biomarkers proved to differentiate all sites, with a very good classification rate for highly contaminated streams. Influence of fish gender and sampling period on biomarker responses was also observed and is discussed. The results of this field study provide additional support for the use of stickleback for in situ multi-biomarker assessment

Copper-induced oxidative stress in three-spined stickleback : relationship with hepatic metal levels

International audienceThe aim of this study was to characterise biomarker responses in three-spined sticklebacks exposed to copper. For this purpose, adult sticklebacks were exposed for 3 weeks to copper sulphate at 0. 25 100 and 200 mug L-1 as Cu. At days 4, 8, 12 and 21. several parameters were measured including liver, gonad and spleen somatic indexes, hepatic biomarkers (catalase (CAT), superoxide dismutase (SOD). glutathione peroxidase (GPx), glutathione (GSH), glutathione-S-transferase (GST) and 7-ethoxyresorufin-O-deethylase (EROD)) and hepatic copper and zinc concentrations. Copper induced a rapid and transient increase of antioxidant enzymes and a depletion of gluiathione content during the first 8 days of exposure. Significant copper and zinc accumulation in fish liver were observed for the two higher exposure concentrations after 8 and 12 days, respectively. This study showed that copper induced an oxidative stress in fish liver before significant metal accumulation in the liver could be detected, suggesting the involvement of differential mechanisms in copper uptake and metabolism. Three-spined stickleback appears to be a sensitive model to stud), oxidative stress induced by metals

Evaluation of an in vitro hsp 70 induction test for toxicity assessment of complex mixtures : comparaison with chemical analyses and ecotoxicity tests

International audienceThe aim of this study was to assess the potential of a human cell line containing the hsp70 promoter linked to the chloramphenicol acetyltransferase reporter gene in evaluating the toxic potential of complex mixtures. Cells were exposed to eluates of industrial wastes and the cellular responses were compared with the metal contents of the samples and with standardized aquatic (microalgal growth inhibition, daphnia Immobilization, bacterial luminescence inhibition, Ceriodaphnia dubia reproduction inhibition) and terrestrial (earthworm lethality, plant growth inhibition) tests. The hsp70 promoter was significantly induced by 11 of 14 samples, with different dose-response patterns. Significant correlations of in vitro induction potency with aquatic ecotoxicity, especially with chronic tests, and with the metal contents of the samples were observed. Our study provides new information on the relevance of hsp70 gene induction as a criterion of toxicity and suggests its usefulness for the detection of toxicity associated with metallic pollution in complex mixtures

Induction of the HSP70 gene promoter by various anticancer drugs

International audienceHeLa cells containing the chloramphenicol acetyl transferase (CAT) gene under the control of the hsp70 promoter have been exposed in vitro to various anticancer drugs. Cisplatin induced CAT production with a dose-effect relationship at a non-cytotoxic dose, whereas no induction was detected with carboplatin. Etoposid induced a significant response at a cytotoxic concentration. The limited positive response with doxorubicin, daunomycin and mitoxantrone was not statistically significant. These chemicals are known to produce reactive oxygen species and induce apoptosis. No induction of the hsp70 promoter could be detected with the other cytostatic compounds that have been tested such as base analogues (5-fluorouracil, cytosine arabinoside 3'-MP), inhibitors of DNA synthesis (amethopterin, aminopterin), antimitotics (vinblastine, colchicine), and alkylating (streptozotocine, carboplatin, melphalan) or intercalating agents (bleomycin). In addition, the role of the transcription inhibitory activity of doxorubicin in this model is evidenced and the consequent question of the suitability of the reporter gene system is discussed. Our results suggest that specific genotoxic compounds are not able to induce the hsp70 promoter, and are in agreement with the concept that stimulation of HSP70 synthesis occurs through a biochemical process involving proteotoxicity

Unconditional cash transfers do not prevent children's undernutrition in the Moderate Acute Malnutrition Out (MAM'Out) cluster-randomized controlled trial in rural Burkina Faso

International audienceBackground: Limited evidence is available on the impact that unconditional cash transfer (UCT) programs can have on child nutrition, particularly in West Africa, where child undernutrition is still a public health challenge.Objective: This study examined the impact of a multiannual, seasonal UCT program to reduce the occurrence of wasting (weight-for-height, midupper arm circumference), stunting (height-for-age), and morbidity among children 0.05) in children's anthropometric measurements and stunting between the 2 groups at the end point. However, children in the intervention group had a lower risk [21% (95% CI: 18.6%, 21.3%); P < 0.001] of self-reported respiratory tract infections than did children in the control group.Conclusions: We found that seasonal UCTs in the framework of safety nets did not result in a significant decrease in the incidence of acute malnutrition among children in Tapoa Province. Cash transfers combined with complementary interventions targeted to child nutrition and health should be investigated further. This trial was registered at clinicaltrials.gov as NCT01866124

The effect of adding ready-to-use supplementary food to a general food distribution on child nutritional status and morbidity : a cluster-randomized controlled trial

Background: Recently, operational organizations active in child nutrition in developing countries have suggested that blanket feeding strategies be adopted to enable the prevention of child wasting. A new range of nutritional supplements is now available, with claims that they can prevent wasting in populations at risk of periodic food shortages. Evidence is lacking as to the effectiveness of such preventive interventions. This study examined the effect of a ready-to-use supplementary food (RUSF) on the prevention of wasting in 6- to 36-mo-old children within the framework of a general food distribution program. Methods and Findings: We conducted a two-arm cluster-randomized controlled pragmatic intervention study in a sample of 1,038 children aged 6 to 36 mo in the city of Abeche, Chad. Both arms were included in a general food distribution program providing staple foods. The intervention group was given a daily 46 g of RUSF for 4 mo. Anthropometric measurements and morbidity were recorded monthly. Adding RUSF to a package of monthly household food rations for households containing a child assigned to the intervention group did not result in a reduction in cumulative incidence of wasting (incidence risk ratio: 0.86; 95% CI: 0.67, 1.11; p = 0.25). However, the intervention group had a modestly higher gain in height-for-age (+0.03 Z-score/mo; 95% CI: 0.01, 0.04; p < 0.001). In addition, children in the intervention group had a significantly higher hemoglobin concentration at the end of the study than children in the control group (+3.8 g/l; 95% CI: 0.6, 7.0; p = 0.02), thereby reducing the odds of anemia (odds ratio: 0.52; 95% CI: 0.34, 0.82; p = 0.004). Adding RUSF also resulted in a significantly lower risk of self-reported diarrhea (-29.3%; 95% CI: 20.5, 37.2; p < 0.001) and fever episodes (-22.5%; 95% CI: 14.0, 30.2; p < 0.001). Limitations of this study include that the projected sample size was not fully attained and that significantly fewer children from the control group were present at follow-up sessions. Conclusions: Providing RUSF as part of a general food distribution resulted in improvements in hemoglobin status and small improvements in linear growth, accompanied by an apparent reduction in morbidity

Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery

BackgroundThe incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. However, the mechanisms by which statins protect the vasculature from irradiation injury remain poorly understood.ObjectivesIdentify the mechanisms by which the hydrophilic and lipophilic statins pravastatin and atorvastatin preserve endothelial function after irradiation.MethodsCultured human coronary and umbilical vein endothelial cells irradiated with 4 Gy and mice subjected to 12 Gy head-and-neck irradiation were pretreated with statins and tested for endothelial dysfunction, nitric oxide production, oxidative stress, and various mitochondrial phenotypes at 24 and 240 h after irradiation.ResultsBoth pravastatin (hydrophilic) and atorvastatin (lipophilic) were sufficient to prevent the loss of endothelium-dependent relaxation of arteries after head-and-neck irradiation, preserve the production of nitric oxide by endothelial cells, and suppress the cytosolic reactive oxidative stress associated with irradiation. However, only pravastatin inhibited irradiation-induced production of mitochondrial superoxide; damage to the mitochondrial DNA; loss of electron transport chain activity; and expression of inflammatory markers.ConclusionsOur findings reveal some mechanistic underpinnings of the vasoprotective effects of statins after irradiation. Whereas both pravastatin and atorvastatin can shield from endothelial dysfunction after irradiation, pravastatin additionally suppresses mitochondrial injury and inflammatory responses involving mitochondria. Clinical follow-up studies will be necessary to determine whether hydrophilic statins are more effective than their lipophilic counterparts in reducing the risk of cardiovascular disease in patients undergoing radiation therapy