Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress

Abstract

Organochalcogens have been widely studied given their antioxidant activity, which confers neuroprotection, antiulcer and antidiabetic properties. Given the complexity of mammalian models, understanding the cellular and molecular effect of organochalcogens has been hampered. The nematode worm Caenorhabditis elegans (C. elegans) is an alternative experimental model that affords easy genetic manipulations, green-fluorescent protein tagging and in vivo live-analysis of toxicity. We previously showed that manganese (Mn)-exposed worms exhibit oxidative-stress-induced neurodegeneration and lifespan reduction. Here we use Mn-exposed worms as a model for an oxidatively challenged organism to investigate the underlying mechanisms of organochalcogen antioxidant properties. First, we recapitulate in C. elegans the effects of organochalcogens formerly observed in mice, including their antioxidant activity. This is followed by studies on the ability of these compounds to afford protection against Mn-induced toxicity. Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) was the most efficacious compound, fully reversing the Mn-induced reduction in survival and lifespan. Ebselen was also effective reversing the Mn-induced reduction in survival and lifespan, but to a lesser extent compared with DPTVP. DPTVP also lowered Mn-induced increases in oxidant levels, indicating that the increased survival associated with exposure to this compound is secondary to a decrease in oxidative stress. Furthermore, DPTVP induced nuclear translocation of the transcriptional factor DAF-16/Foxo, which regulates stress responsiveness and aging in worms. Our findings establish that the organochalcogens DPTVP as well as ebselen act as anti-aging agents in a model of Mn-induced toxicity and aging by regulating DAF-16/Foxo signaling and attenuating oxidative stress.

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

“…Figure 3 shows the percentage of survival versus logarithmic dose of nanocapsules. The LD 50 for LNC was 105.90×10 12 LNC/mL, and the PS80-group did not show mortality after acute exposure. All of the tested doses were compared to the control group, which did not receive the treatment.…”

“…Eggs were washed with M9 buffer (0.02 M KH 2 PO 4 , 0.04 M Na 2 HPO 4 , 0.08 M NaCl, and 0.001 M MgSO 4 ) and allowed to hatch overnight in NGM agar plates without bacteria. 50 evaluation of absorption and distribution of Mel-LNC in C. elegans…”

“…The LD 50 of LNC was determined in C. elegans after acute exposure to six doses ranging from 2.37×10 12 to 118.5×10 12 LNC/mL (Table 1). Two thousand five hundred synchronized L1 worms per dose were treated at 20°C for 30 minutes by constant agitation in a rotator with each dose of the compounds.…”

Ebselen Alters Mitochondrial Physiology and Reduces Viability of Rat Hippocampal Astrocytes

“…Ebselen acts as an antiaging agent by attenuating oxidative stress in Caenorhabditis elegans (Avila et al, 2012), protects neurons from ischemic damage via control of the expressions of GABA shunt enzymes (Seo et al, 2009), has a marked inhibitory effect on neuronal damage during stroke (Yamagata et al, 2008), protects against excitotoxicity induced by glutamate in isolated chick retina (Centuriã o et al, 2005), and prevents ischemia-induced cytotoxicity and apoptosis (Gabryel and Ma1ecki, 2006) and reactive oxygen species (ROS) production (Pérez-Ortiz et al, 2004) in astrocytes.…”

Differential genotoxicity of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2

“…Literature has demonstrated immunomodulatory, antioxidant and anticancer properties of various organotellurides (Nogueira, Zeni & Rocha, 2004;Avila et al, 2012), semisynthetic tellurosubtilisin (Mao et al, 2005) and dendrimeric organotellurides (Francavilla et al, 2001). More sophisticated telluride molecules were synthesized from polystyrene nanoparticle via microemulsion polymerization.…”