Zinc contamination is an underestimated risk to amphibians: toxicity evaluation in tadpoles of Fejervarya limnocharis

Aquatic environments are often contaminated with zinc. Amphibian tadpoles are likely to be exposed to high concentrations of zinc present in these environments. We determined the acute and sub-chronic toxicity of ZnCl2 on Fejervarya limnocharis tadpoles under laboratory conditions. The LC50 values of ZnCl2 were found to be 5.81, 4.32, 3.79 and 3.61 mg/L at 24, 48, 72 and 96 h of exposure respectively. Long-term exposure to sub-lethal concentrations of ZnCl2 induced significant mortality in concentration and time dependent manner. Sub-lethal ZnCl2 exposure significantly altered survival, body length and body weight at metamorphosis. Micronucleus test and comet assay indicated the genotoxic potential of ZnCl2. Significant increase in DNA strand break was observed following ZnCl2 exposure equivalent to 1% of the of 24 h LC50 value. The findings indicate possible adverse to tadpoles inhabiting aquatic environments contaminated with zinc. In addition, the findings may be extrapolated to aquatic organisms of similar torphic status

Chronic exposure of homocysteine in mice contributes to dopamine loss by enhancing oxidative stress in nigrostriatum and produces behavioral phenotypes of Parkinson’s disease

AbstractIncreased homocysteine (Hcy) level has been implicated as an independent risk factor for various neurological disorders, including Parkinson’s disease (PD). Hcy has been reported to cause dopaminergic neuronal loss in rodents and causes the behavioral abnormalities. This study is an attempt to investigate molecular mechanisms underlying Hcy-induced dopaminergic neurotoxicity after its chronic systemic administration. Male Swiss albino mice were injected with different doses of Hcy (100 and 250mg/kg; intraperitoneal) for 60 days. Animals subjected to higher doses of Hcy, but not the lower dose, produces motor behavioral abnormalities with significant dopamine depletion in the striatum. Significant inhibition of mitochondrial complex-I activity in nigra with enhanced activity of antioxidant enzymes in the nigrostriatum have highlighted the involvement of Hcy-induced oxidative stress. While, chronic exposure to Hcy neither significantly alters the nigrostriatal glutathione level nor it causes any visible change in tyrosine hydroxylase-immunoreactivity of dopaminergic neurons. The finding set us to hypothesize that the mild oxidative stress due to prolonged Hcy exposure to mice is conducive to striatal dopamine depletion leading to behavioral abnormalities similar to that observed in PD

A Systems Biology Approach Reveals a Calcium-Dependent Mechanism for Basal Toxicity in Daphnia magna.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science & Technology, copyright © American Chemical Society after peer review and technical editing by the publisher.The expanding diversity and ever increasing amounts of man-made chemicals discharged to the environment pose largely unknown hazards to ecosystem and human health. The concept of adverse outcome pathways (AOPs) emerged as a comprehensive framework for risk assessment. However, the limited mechanistic information available for most chemicals and a lack of biological pathway annotation in many species represent significant challenges to effective implementation of this approach. Here, a systems level, multistep modeling strategy demonstrates how to integrate information on chemical structure with mechanistic insight from genomic studies, and phenotypic effects to define a putative adverse outcome pathway. Results indicated that transcriptional changes indicative of intracellular calcium mobilization were significantly overrepresented in Daphnia magna (DM) exposed to sublethal doses of presumed narcotic chemicals with log Kow ≥ 1.8. Treatment of DM with a calcium ATPase pump inhibitor substantially recapitulated the common transcriptional changes. We hypothesize that calcium mobilization is a potential key molecular initiating event in DM basal (narcosis) toxicity. Heart beat rate analysis and metabolome analysis indicated sublethal effects consistent with perturbations of calcium preceding overt acute toxicity. Together, the results indicate that altered calcium homeostasis may be a key early event in basal toxicity or narcosis induced by lipophilic compounds

Évaluation des caractéristiques physico-chimiques de l'eau dans certaines stations du lac Tanganyika, en Afrique, avec un accent particulier sur les objectifs de la piscicoles

International audienceThe current limnological study was carried out on Lake Tanganyika in 4 sampling sites to assess the physico-chemical properties and trophic status for pisciculture purpose. The estimated values of physical and chemical parameters of water samples were compared to the desirable, permissible and acceptable ranges for pisciculture recommended standards. In this regards, 9 physico-chemical parameters have been analyzed and the results of the comparative analysis showed that most of the water quality parameters were suitable for fish culture because 7important parameters (77.8%) were within the permissible limits and 2parameters (22.2%) were found inappropriate for pisciculture. The values of transparency, chlorophyll a and Total phosphorus revealed clearly that all sampling stations were in hypereutrophic status which indicate eutrophication phenomenon.La présente étude limnologique a été réalisée sur le lac Tanganyika dans 4 sites d'échantillonnage pour évaluer les propriétés physico-chimiques et l'état trophique à des fins piscicoles. Les valeurs estimées des paramètres physiques et chimiques des échantillons d'eau ont été comparées aux plages souhaitables, permises et acceptables pour les normes recommandées pour la pisciculture. À cet égard, 9 paramètres physico-chimiques ont été analysés et les résultats de l'analyse comparative ont montré que la plupart des paramètres de qualité de l'eau étaient adaptés à la pisciculture car 7 paramètres importants (77,8%) se situaient dans les limites autorisées et 2 paramètres (22,2%). ont été jugés inappropriés pour la pisciculture. Les valeurs de transparence, de chlorophylle a et de phosphore total ont clairement révélé que toutes les stations d'échantillonnage étaient en état hypereutrophique, ce qui indique un phénomène d'eutrophisation

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia

Effect of hypercholesterolemia on nigrostriatal mitochondrial complex-III activity in Parkinsonian mice.

<p>(A-D) representative striatal (NCP) sections and (E-H) substantia nigral (SN) sections were processed for mitochondrial complex-III activity by employing histoenzymology. The marked region in the photographs (E-H) represents substantia nigra pars compacta (SNpc) region [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0171285#pone.0171285.ref059" target="_blank">59</a>]. Optical density of serial sections of (I) NCP and (J) SN was analyzed using ImageJ software. The results are given as mean ± S.E.M. *p ≤ 0.05 as compared to control (CS) and #p ≤ 0.05 as compared to MPTP alone treated group (n = 4).</p

Effect of hypercholesterolemia on hydroxyl radical (•OH) generation in (A,C,E) striatum and (B,D,F) substantia nigra regions of brain of Parkinsonian mice.

<p>Animals were injected with salicylic acid (100 mg/kg) and sacrificed two hours post injection on the last day of treatment. 2,3- and 2,5-dihydroxy benzoic acid (DHBA; •OH adducts of salicylate) formed were measured from homogenates of NCP and SN by employing a sensitive HPLC-ECD method. Data are expressed as pmol/mg tissue and represented as mean ± S.E.M. *p ≤ 0.05 as compared with control and #p ≤ 0.05 as compared with MPTP alone treated group (n = 5).</p

Effect of hypercholesterolemia on nigrostriatal reduced glutathione (GSH) level in Parkinsonian mice.

<p>(A) Striatum and (B) substantia nigra regions of brain were used for estimating GSH levels by employing a sensitive HPLC-ECD system. Data are expressed as nmol/mg tissue and represented as mean ± S.E.M. *p ≤ 0.05 as compared with control and #p ≤ 0.05 as compared with MPTP alone treated group (n = 5).</p

Effect of hypercholesterolemia on striatal dopamine level in Parkinsonian mice.

<p>Mice were sacrificed by decapitation on the seventh day following the first dose of MPTP. Striatal dopamine content was analyzed by HPLC-ECD system. Hypercholesterolemia exaggerates striatal dopamine depletion in Parkinsonian mice. The results are given as mean ± S.E.M. *p ≤ 0.05 as compared to control (CS) and #p ≤ 0.05 as compared to MPTP alone treated group (n = 6).</p

Effect of hypercholesterolemia on Parkinsonian motor behavior.

<p>In the last week of the 14 week treatment period, all the groups of animals were tested for (A) akinesia (B) catalepsy and (C) Swim test. The results are given as mean ± S.E.M. *p ≤ 0.05 as compared to control (CS) and #p ≤ 0.05 as compared to MPTP alone treated group (n = 6).</p