Hydroalcoholic extract of Haematoxylum brasiletto protects Caenorhabditis elegans from cadmium-induced toxicity.

BACKGROUND: H. brasiletto is used in popular culture due to its therapeutic properties, including antioxidant, anti-inflammatory and antiproliferative properties, although little is known about its role as a protector against metal toxicity. This study aimed to investigate the chemical composition and efficacy of the hydroalcoholic extract from H. brasiletto (HAE-Hbrasiletto) collected in northern Colombia to defend against cadmium (Cd)-induced toxicity. METHODS: Phytochemical characterization was performed using HPLC-ESI-QTOF. Caenorhabditis elegans was employed to assess the shielding effect of HAE-Hbrasiletto against Cd toxicity in vivo, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was utilized to measure radical scavenging activity. RESULTS: The main secondary metabolites identified by HPLC-ESI-QTOF in the extracts were hematoxylins (brazilein and hematein) and protosappanins (protosappanin A, B and C, 10-O-methylprotosappanin B, and protosappanin A dimethyl acetal). The HAE-Hbrasiletto elicited low lethality in N2 worms and significantly reduced the Cd-induced death of the nematodes. It also improved Cd-induced motility inhibition, as well as body length and reproduction reduction provoked by the heavy metal. The extract displayed a good capacity to halt Cd-induced DAF-16 translocation. As this last process was associated with lethality (r = 0.962, p < 0.01), the antioxidant properties of the extract may contribute to ameliorating tissue damage induced by oxidative stress from Cd exposure. CONCLUSION: HAE-Hbrasiletto has remarkable properties to protect against Cd-induced toxicity.

Glyphosate-based herbicides modulate oxidative stress response in the nematode Caenorhabditis elegans.

Glyphosate-based formulation is used as non-selective and post-emergent herbicides in urban and rural activities. In view of its recurring applications in agricultural producing countries, the increase of glyphosate concentration in the environment stresses the need to test the adverse effects on non-target organisms and assess the risk of its use. This paper analyzes the toxicological and oxidative stress and modulatory effects of a glyphosate commercial formulation (glyphosate F) on the nematode Caenorhabditis elegans. We detected ROS production and enhancement of oxidative stress response in glyphosate F-treated nematodes. Particularly, we found an increased ctl-1 catalase gene expression of a catalase specific activity. In addition, we showed that glyphosate F treatment activated the FOXO transcription factor DAF-16, a critical target of the insulin/IGF-1 signaling pathway, which modulates the transcription of a broad range of genes involved in stress resistance, reproductive development, dauer formation, and longevity. In summary, the exposure of glyphosate F induces an oxidative imbalance in C. elegans that leads to the DAF-16 activation and consequently to the expression of genes that boost the antioxidant defense system. In this regard, clt-1 gene and catalase activity proved to be excellent biomarkers to develop more sensitive protocols to assess the environmental risk of glyphosate use.

Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans.

Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4-phenylchalcogenil-7-chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium-containing compounds). While non-lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat-induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF-16/FOXO and SKN-1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod-3, gst-4 and gcs-1 were modulated following exposures in a daf-16- and skn-1-dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr-1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches.

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

BACKGROUND: Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. SCOPE: Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. CONCLUSION: DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches.

Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans.

AIMS: Vitellogenesis is the yolk production process which provides the essential nutrients for the developing embryos. Yolk is a lipoprotein particle that presents lipids and lipid-binding proteins, referred to as vitellogenins (VIT). The Caenorhabditis elegans nematode has six genes encoding VIT lipoproteins. Several pathways are known to regulate vitellogenesis, including the DAF-16 transcription factor. Some reports have shown that heavy metals, such as manganese (Mn), impair brood size in C. elegans; however the mechanisms associated with this effect have yet to be identified. Our aim was to evaluate Mn's effects on C. elegans reproduction and better understand the pathways related to these effects. MAIN METHODS: Young adult larval stage worms were treated for 4h with Mn in 85mM NaCl and Escherichia coli OP50 medium. KEY FINDINGS: Mn reduced egg-production and egg-laying during the first 24h after the treatment, although the total number of progenies were indistinguishable from the control group levels. This delay may have occurred due to DAF-16 activation, which was noted only after the treatment and was not apparent 24h later. Moreover, the expression, protein levels and green fluorescent protein (GFP) fluorescence associated with VIT were decreased soon after Mn treatment and recovered after 24h. SIGNIFICANCE: Combined, these data suggest that the delay in egg-production is likely regulated by DAF-16 and followed by the inhibition of VIT transport activity. Further studies are needed to clarify the mechanisms associated with Mn-induced DAF-16 activation.

Seleno- and telluro-xylofuranosides attenuate Mn-induced toxicity in C. elegans via the DAF-16/FOXO pathway.

Organochalcogens are promising pharmacological agents that possess significant biological activities. Nevertheless, because of the complexity of mammalian models, it has been difficult to determine the molecular pathways and specific proteins that are modulated in response to treatments with these compounds. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging and in vivo live analysis of toxicity. Abundant evidence points to oxidative stress in mediating manganese (Mn)-induced toxicity. In this study we challenged worms with Mn, and investigated the efficacy of inedited selenium- and tellurium-xylofuranosides in reversing and/or protecting the worms from Mn-induced toxicity. In addition, we investigated their putative mechanism of action. First, we determined the lethal dose 50% (LD50) and the effects of the xylofuranosides on various toxic parameters. This was followed by studies on the ability of xylofuranosides to afford protection against Mn-induced toxicity. Both Se- and Te-xylofuranosides increased the expression of superoxide dismutase (SOD-3). Furthermore, we observed that the xylofuranosides induced nuclear translocation of the transcription factor DAF-16/FOXO, which in the worm is known to regulate stress responsiveness, aging and metabolism. These findings suggest that xylofuranosides attenuate toxicity Mn-induced, by regulating the DAF-16/FOXO signaling pathway.

Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans

Electrolyzed-reduced water (ERW) scavenges reactive oxygen species and is a powerful anti-oxidant. A positive correlation between oxidative stress and aging has been proved in many model organisms. In Caenorhabditis elegans, many long-lived mutants showed reduced fertility as a trade off against longevity phenotype. We aimed to study the effect of ERW on oxidative stress, fertility and lifespan of C. elegans. We also investigated the genetic pathway involved in the effect of ERW on resistance to oxidative stress and lifespan. We compared lifespan and fertility of worms in media prepared with distilled water and ERW. ERW significantly extended lifespan and increased the number of progeny produced. Then the effect of ERW on resistance to oxidative stress and lifespan of long-lived mutants was determined. ERW increased resistance to oxidative stress and lifespan of eat-2, a genetic model of dietary restriction, but had no effect on those of age-1, which is involved in insulin/insulin-like growth factor (IGF)-1-like signal. In addition, knockdown of daf-16, the downstream mediator of insulin/IGF-1-like signal, completely prevented the effect of ERW on lifespan. These findings suggest that ERW can extend lifespan without accompanying reduced fertility and modulate resistance to oxidative stress and lifespan via insulin/IGF-1-like signal in C. elegans.