The Endocannabinoid System in Caenorhabditis elegans.

The existence of a formal Endocannabinoid System in C. elegans has been questioned due to data showing the absence of typical cannabinoid receptors in the worm; however, the presence of a full metabolism for endocannabinoids, alternative ligands, and receptors for these agents and a considerable number of orthologous and homologous genes regulating physiological cannabinoid-like signals and responses - several of which are similar to those of mammals - demonstrates a well-structured and functional complex system in nematodes. In this review, we describe and compare similarities and differences between the Endocannabinoid System in mammals and nematodes, highlighting the basis for the integral study of this novel system in the worm.

(p-ClPhSe)2 modulation on carbohydrate and lipid metabolism requires the insulin-like signaling in Caenorhabditis elegans.

Organoselenium compounds modulate the metabolism by regulating carbohydrate and lipid syntheses and degradation in the liver, muscle, and adipose tissue. Notably, p-chloro-diphenyl diselenide (p-ClPhSe)2 can directly regulate the activities of enzymes involved in glucose metabolism, suggesting an insulin-like effect in rodents; however, there is still a lack of scientific evidence to confirm this hypothesis. The objective of this study was to investigate (p-ClPhSe)2 effects on glucose and lipid metabolism in Caenorhabditis elegans. The contribution of AGE-1/PI3K, AKT-1, AKT-2, PFK-1, DAF-16, and DAF-2 in the (p-ClPhSe)2 effects were also investigated. Our results demonstrate that (p-ClPhSe)2 acute exposure presented some toxicity to the worms, and therefore, lower concentrations were further used. (p-ClPhSe)2 reduced glucose and triglyceride levels to the baseline levels, after induction with glucose or fructose, in wild-type worms. This effect required proteins involved in the insulin/IGF-1 like signaling, such as the DAF-2, AGE-1, AKT-1 and AKT-2, PFK-1, but also DAF-16, which would be negatively regulated by DAF-2 activation. Moreover, the reduction in glucose and triglyceride levels, caused by (p-ClPhSe)2per se was lost in age-1/daf-16 worms, suggesting that insulin/IGF-1-like signaling in a DAF-2 and AGE-1/DAF-16 dependent-manner in C. elegans are necessary to effects of (p-ClPhSe)2. In conclusion, (p-ClPhSe)2 requires proteins involved in the IIS pathway to modulate carbohydrate and lipid metabolism.

Bougainvillea glabra Choisy bracts extract in free and liposomal forms reduce hyperplasia induced by let-60gain-of-function in Caenorhabditis elegans.

In this study, we evaluated the toxicological and antiproliferative effects of B. glabra Choisy bract extract (BGCE) in its free and loaded into liposomes forms administered to C. elegans mutants with let-60 gain-of-function (gf). Our results demonstrated that the concentration up to 75 µg CAE/mL of BGCE was safe for the worms. Notably, we developed BGCE-loaded liposomes to extend the pharmacological window up to 100 µg CAE/mL without toxicity. In addition, the extract and liposomes reduced the number and area of the multivulva formed in let-60 gf mutants. There was also an increase in the apoptotic signaling in the germline cells and increased longevity mediated through DAF-16 nuclear translocation with GST-4 activation in the treated animals. Our findings demonstrated that the BGCE-loaded liposomes possess antitumoral effects due to the activation of the apoptotic signaling and DAF-16 nuclear translocation.

Grape juice reduces the effects of amyloid ß aggregation phenotype and extends the longevity in Caenorhabditis elegans.

OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of aggregated amyloid-ß (Aß) peptides. Several natural compounds have been proposed against this disease and grape products are among these. However, little is known about grape juice potential. Transgenic Caenorhabditis elegans (C. elegans) strains that express human Aß have been used as an in vivo model for AD. METHODS: In this study, we have exposed CL2006 worms to nine different juices obtained from different cultivars. RESULTS: Cora, Bordo, Isabel, Isabel Precoce, BRS-Magna, BRS-Rubea and BRS-Violeta juices improved the behavioral phenotype (paralysis) that is caused by Aß aggregation in the transgenic animals at the concentrations tested and no toxic effects were found. Some juices were also able to increase the worm's lifespan. We could not attribute lifespan increase and paralysis reduction with any specific compound found in the phytochemical analysis. DISCUSSION: Our data indicate that the rich constitution of the juices is responsible for attenuating the phenotype caused by Aß aggregation in C. elegans.

Purple pitanga extract (Eugenia uniflora) attenuates oxidative stress induced by MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely used due to its specific and reproducible neurotoxic effect on the nigrostriatal system, being considered a convenient model of dopaminergic neurodegeneration to study interventions therapeutics. The purple pitanga (Eugenia uniflora) is a polyphenol-rich fruit with antioxidant and antidepressant properties, among others. Therefore, this study investigated the effect of purple pitanga extract (PPE) on acute early oxidative stress induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats. Male Wistar rats were pre-treated orally with PPE (1000 mg/kg) or vehicle. After 24 h, MPTP (0.1 mg/10µL/nostril) or vehicle was administered bilaterally into the animal's nostrils, and 6 h later, the olfactory bulb (OB), striatum (ST), and substantia nigra (SN) were collected to evaluate the oxidative stress parameters. Our findings revealed that OB and SN were the most affected areas after 6 h of MPTP infusion; an early increase in reactive oxygen species (ROS) levels was observed, while pretreatment with a single dose of PPE prevented this increment. No differences in thiobarbituric acid reactive species (TBARS) and 3-nitrotyrosine (3-NT) formation were observed, although 4-hydroxy-2-nonenal (4-HNE) levels increased, which is the most toxic form of lipid peroxidation, in the MPTP group. The PPE pretreatment could prevent this increase by increasing the NPSH levels previously decreased by MPTP. Furthermore, PPE prevents the Na+/K + ATPase strongly inhibited by MPTP, showing the neuroprotective capacity of the PPE by inhibiting the MPTP-generated oxidation. Thus, we demonstrated for the first time the antioxidant and neuroprotective effects of PPE against the early MPTP neurotoxicity.

Reprotoxicity induced by acute exposure to aqueous tuber extract of Peruvian Maca (Lepidium meyenii Walp.) in Caenorhabditis elegans.

Maca (Lepidium meyenii Walp.) has been used in folk medicine to treat fertility disturbances, a claim that has been evidenced in some studies. However, the clinical trials validating this use have shown paradoxical findings and then maca safety is not well known. This study investigated the effects and mechanisms by which maca affects the reproductive system using an in vivo model, the nematode Caenorhabditis elegans. Tuber maca powder, obtained from local commerce, was used to prepare the aqueous extract. Worms were acutely exposed to maca extracts (40, 120, 240, and 330 µg/µl), and 48 h after treatments, physiological and biochemical assays were conducted. Maca extract caused a significant decrease in total number of eggs and in the number of eggs per worm. These effects were associated to increased lipid peroxidation, reduced triacylglycerol levels, and also impaired vit-2 (vitellogenin) expression, besides increase in the number of apoptotic germline cells. We have found quantifiable levels of alkaloids in this maca extract, which presence could be related to this toxicity. Collectively, our data suggest that maca extract exposure causes reproductive toxicity to worms that could be, at least in part, associated to both an increase in apoptosis of germline cells and also to a decrease in vitellogenin expression, needed for egg yolk production and, consequently, successful reproduction.

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans.

Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1-benzylpiperazine (BZP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC50 for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm, respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.

Lipid reducing potential of liposomes loaded with ethanolic extract of purple pitanga (Eugenia uniflora) administered to Caenorhabditis elegans.

The ethanolic extract obtained from purple pitanga fruit (Eugenia uniflora - PPE) has been previously described by its potential to reduce lipid accumulation in vitro. In this study, we aimed to study this potential in vivo using Caenorhabditis elegans as animal model. Considering the low pH of the extract, its hydrophilic characteristic, its absorption by the medium where the worms are cultivated and the need of a chronic exposure in the worms solid medium, we have loaded liposomes with PPE and investigated its potential for oral administration. Following 48 h exposure to the PPE-loaded liposomes on worms nematode growth medium, we did not observe any toxic effects of the formulation. Under high cholesterol diet, which increased worms total lipid and also triacylglycerides levels, liposomes containing PPE were able to significantly attenuate these alterations, which could not be observed when worms were treated with free PPE. Furthermore, we could evidence that liposomes were ingested by worms through their labelling to uranin fluorescence dye. Through total phenolic compounds quantification, we estimated an entrapment efficacy of PPE into liposomes of 87.7%. The high levels of phenolic compounds present in PPE, as previously described by our group, indicate that these antioxidants may interfere in worms lipid metabolism, which may occur through many and intricated mechanisms. Although the use of conventional liposomes for human consumption may not be pragmatic, its application for oral delivery of a hydrophilic substance in C. elegans was absolutely critical for our experimental design and has proven to be efficient.

Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment.

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 24 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.

Safety assessment of nanopesticides using the roundworm Caenorhabditis elegans.

The extensive use of pesticides is causing environmental pollution, affecting animal organisms in different habitats and also leading human health at risk. In this study, we present as an alternative the use of nanoparticles loaded with pesticides and report their toxicological assessment to a soil organism, Caenorhabditis elegans. Three nanoparticle formulations were analyzed: solid lipid nanoparticles loaded or not with atrazine and simazine, SLN; polymeric nanoparticles, NC_PCL loaded with atrazine; and chitosan/tripolyphosphate, CS/TPP, loaded or not with paraquat. All formulations, loaded or not with pesticides, increased lethality in a dose- dependent manner with similar LC50. Both loaded and unloaded NC_PCL were the most toxic formulations to developmental rate, significantly reducing worms length, even at low concentrations. In contrast, both CS/TPP nanoparticles were the least toxic, not affecting reproduction and body length at higher concentrations, probably due to the biocompatibility of chitosan. The physico-chemical characterization of nanoparticles after incubation in saline solution (used in exposure of organisms) has shown that these colloidal systems are stable and remain with the same initial characteristics, even in the presence of saline environment. Notably, our results indicate that the observed effects were caused by the nanoparticles per se. These results suggest that the development of nanoparticles aiming agriculture applications needs more studies in order to optimize the composition and then reduce their toxicity to non-target organisms.

Ilex paraguariensis crude extract acts on protection and reversion from damage induced by t-butyl hydroperoxide in human erythrocytes: a comparative study with isolated caffeic and/or chlorogenic acids.

BACKGROUND: Studies comparing the effects of phytochemicals under different regimens of exposure are necessary to give a better indication about their mechanism(s) of protection. Hence, in the present study, we investigated the preventive (pre-incubation), protective (co-incubation) and/or remediative (post-incubation) activity of chlorogenic acid and caffeic acids, in comparison with Ilex paraguariensis crude extract, against t-butyl hydroperoxide (t-BHP)-induced damage to human erythrocytes. RESULTS: We found that both caffeic and chlorogenic acids were able to prevent and revert the hemolysis associated with t-BHP exposure. By contrast, isolated compounds (alone or in combination) presented no effect on basal and/or t-BHP-induced non-protein thiol (NPSH) oxidation or production of thiobarbituric acid reactive substances (TBBARS). In turn, I. paraguariensis extract was effective to prevent, protect and revert the hemolysis associated with t-BHP exposure. Moreover, I. paraguariensis significantly protects and reverts t-BHP-induced NPSH oxidation and TBARS production. CONCLUSIONS: We have found that I. paraguariensis extract acts better with respect to the protection and reversion of t-BHP-associated changes, whereas isolated compounds are more active in preventing and reverting t-BHP pro-hemolytic action. Moreover, our data suggest that the pro-hemolytic activity of t-BHP may occur via mechanism(s) other(s) than lipid peroxidation and/or NPSH oxidation. © 2016 Society of Chemical Industry.

Clozapine-Loaded Polysorbate-Coated Polymeric Nanocapsules: Physico-Chemical Characterization and Toxicity Evaluation in Caenorhabditis elegans Model.

The aim of this work was to develop and characterize clozapine loaded polysorbate-coated polymeric nanocapsules and assess their toxicity in Caenorhabditis elegans, an invertebrate animal model. Formulations were prepared by nanoprecipitation method and characterized by particle size, zeta potential, pH, drug loading, entrapment efficiency and in vitro drug release. All nanocapsules prepared presented diameter around 140 nm, pH slightly acid and negative zeta potential. In vitro studies showed biphasic drug release from nanocapsules with decreasing of the release rate on nanoencapsulation. The t(1/2)beta of clozapine was 7.23 +/- 0.73 and 2.23 +/- 0.97 h for nanoencapsulated and free drug, respectively (p < 0.05), in pH 1.2 medium. Similar results were obtained in pH 6.8 buffer. Regarding toxicity evaluation, worms exposed to clozapine-loaded nanocapsules did not show the same mortality rate compared to others formulations, as the survival was significantly higher than the free drug treated-group. In addition, we observed that free clozapine decreased egg laying at the first reproductive day, whereas nanoencapsulated clozapine did not depict significant change of this parameter. Longevity assay showed no significant difference, demonstrating that the toxicological effects of clozapine observed in C. elegans are acute. In addition, we proved that free and nanoencapsulated clozapine were orally uptake by the worms, as determined by fluorescein-labeled nanocapsules. Then, the use of nanocapsules delayed the drug release and minimized the toxic effects of clozapine in worms, which can be used as a new animal model to evaluate the nanotoxicity of drug delivery systems.

Using Low-cost Dyes to Visualize Glycogen Accumulation and Gut Integrity in Caenorhabditis elegans.

Caenorhabditis elegans (C. elegans) is a transparent, non-parasitic nematode with a simple biology, which makes it a great tool for biological sciences teaching through the staining of the cells or their molecular content. Lugol dye (iodine-potassium iodide solution) has been widely used in biochemistry to stain glycogen stores. In this context, it is possible to observe differences between fed and starved animals, besides the effects of different conditions, such as different diets and oxygen levels. Erioglaucine is a blue dye that indicates the loss of the intestinal barrier. When the intestinal barrier is intact, the blue dye stains inside the lumen; however, when this integrity is disrupted, the dye leaks into the body cavity. Using a stereomicroscope or a microscope, teachers can demonstrate physiological and biochemical alterations, or they can instigate students to ask a scientific question and hypothesize and test their hypothesis using these assays. The present protocol describes two staining techniques in C. elegans that can be easily carried out by students.

The Caenorhabditis elegans neuroendocrine system and their modulators: An overview.

In this review we seek to systematically bring what has been published in the literature about the nervous system, endocrine system, neuroendocrine relationships, neuroendocrine modulations and endocrine disruptors in the alternative model Caenorhabditis elegans. The serotonergic, dopaminergic, GABAergic and glutamatergic neurotransmitters are related to the modulation of the neuroendocrine axis, leading to the activation or inhibition of several processes that occur in the worm through distinct and interconnected pathways. Furthermore, this review addresses the gut-neuronal axis as it has been revealed in recent years that gut microbiota impacts on neuronal functions. This review also approaches xenobiotics that can positively or negatively impact the neuroendocrine system in C. elegans as in mammals, which allows the application of this nematode to screen new drugs and to identify toxicants that are endocrine disruptors.

Extracellular dopamine potentiates mn-induced oxidative stress, lifespan reduction, and dopaminergic neurodegeneration in a BLI-3-dependent manner in Caenorhabditis elegans.

Parkinson's disease (PD)-mimicking drugs and pesticides, and more recently PD-associated gene mutations, have been studied in cell cultures and mammalian models to decipher the molecular basis of PD. Thus far, a dozen of genes have been identified that are responsible for inherited PD. However they only account for about 8% of PD cases, most of the cases likely involving environmental contributions. Environmental manganese (Mn) exposure represents an established risk factor for PD occurrence, and both PD and Mn-intoxicated patients display a characteristic extrapyramidal syndrome primarily involving dopaminergic (DAergic) neurodegeneration with shared common molecular mechanisms. To better understand the specificity of DAergic neurodegeneration, we studied Mn toxicity in vivo in Caenorhabditis elegans. Combining genetics and biochemical assays, we established that extracellular, and not intracellular, dopamine (DA) is responsible for Mn-induced DAergic neurodegeneration and that this process (1) requires functional DA-reuptake transporter (DAT-1) and (2) is associated with oxidative stress and lifespan reduction. Overexpression of the anti-oxidant transcription factor, SKN-1, affords protection against Mn toxicity, while the DA-dependency of Mn toxicity requires the NADPH dual-oxidase BLI-3. These results suggest that in vivo BLI-3 activity promotes the conversion of extracellular DA into toxic reactive species, which, in turn, can be taken up by DAT-1 in DAergic neurons, thus leading to oxidative stress and cell degeneration.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans.

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

Impaired physiological responses and neurotoxicity induced by a chlorpyrifos-based formulation in Caenorhabditis elegans are not solely dependent on the active ingredient.

The current massive and indiscriminate agrochemicals usage, which is inexorably linked to the toxic consequences to the environment and people, represents a great concern. Our work aimed to compare the toxicity induced by chlorpyrifos in its pure form (CPF) with that of a commercial formulation containing allegedly inert ingredients (CBCF) using Caenorhabditis elegans as in vivo model. After a 48 h exposure period, CBCF was 14 times more lethal than CPF; Hatching, brood size, body length and motor-related behavioral parameters were decreased, but these effects were significantly higher in CBCF-exposed worms. Additionally, CBCF induced significant morphological changes in cholinergic neurons, which are associated with the motor-related behavioral parameters. Finally, by analyzing the CBCF, we detected the presence of potentially-toxic metals that were not specified in the label. The presented results highlight the toxicological relevance of components present in the commercial formulations of pesticides, which have been claimed as inert compounds.

Iron oxide/silver hybrid nanoparticles impair the cholinergic system and cause reprotoxicity in Caenorhabditis elegans.

Iron oxide nanoparticles present superparamagnetic properties that enable their application in various areas, including drug delivery at specific locations in the organism. Silver nanoparticles have potent antimicrobial effects. Although the combination of Fe3O4-NPs and Ag-NPs in one hybrid nanostructure (Fe3O4@Ag-NPs) demonstrated promising targeted biomedical applications, their toxicological effects are unknown and need to be assessed. Caenorhabditis elegans is a promising model for nanotoxicological analysis, as it allows an initial screening of new substances. After exposure to Fe3O4-NPs, Ag-NPs and Fe3O4@Ag-NPs, we observed that hybrid NPs reduced the C. elegans survival and reproduction. Higher concentrations of Fe3O4@Ag-NPs caused an increase in cell apoptosis in the germline and a decrease in egg laying, which was associated with a decrease in worm swimming movements and abnormalities in the cholinergic neurons. Fe3O4@Ag-NPs caused an increase in reactive oxygen species, along with activation of DAF-16 transcription factor. A higher expression of the target genes GST-4::GFP and SOD-3::GFP were evidenced, which suggests the activation of the antioxidant system. Our results indicate the reprotoxicity caused by high levels of Fe3O4@Ag-NPs, as well as cholinergic neurotoxicity and activation of the antioxidant system in C. elegans, suggesting that high concentrations of these nanomaterials can be harmful to living organisms.

Development and In Vivo Assessment of 4-Phenyltellanyl-7-chloroquinoline-loaded Polymeric Nanocapsules in Alzheimer's Disease Models.

Alzheimer's disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aß1-42 in their body-wall muscles and Swiss mice injected with Aß25-35. The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aß peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aß injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.

Mitochondria in the Spotlight: C. elegans as a Model Organism to Evaluate Xenobiotic-Induced Dysfunction.

Mitochondria play a crucial role in cellular respiration, ATP production, and the regulation of various cellular processes. Mitochondrial dysfunctions have been directly linked to pathophysiological conditions, making them a significant target of interest in toxicological research. In recent years, there has been a growing need to understand the intricate effects of xenobiotics on human health, necessitating the use of effective scientific research tools. Caenorhabditis elegans (C. elegans), a nonpathogenic nematode, has emerged as a powerful tool for investigating toxic mechanisms and mitochondrial dysfunction. With remarkable genetic homology to mammals, C. elegans has been used in studies to elucidate the impact of contaminants and drugs on mitochondrial function. This review focuses on the effects of several toxic metals and metalloids, drugs of abuse and pesticides on mitochondria, highlighting the utility of C. elegans as a model organism to investigate mitochondrial dysfunction induced by xenobiotics. Mitochondrial structure, function, and dynamics are discussed, emphasizing their essential role in cellular viability and the regulation of processes such as autophagy, apoptosis, and calcium homeostasis. Additionally, specific toxins and toxicants, such as arsenic, cadmium, and manganese are examined in the context of their impact on mitochondrial function and the utility of C. elegans in elucidating the underlying mechanisms. Furthermore, we demonstrate the utilization of C. elegans as an experimental model providing a promising platform for investigating the intricate relationships between xenobiotics and mitochondrial dysfunction. This knowledge could contribute to the development of strategies to mitigate the adverse effects of contaminants and drugs of abuse, ultimately enhancing our understanding of these complex processes and promoting human health.