Intestinal Reactive Oxygen Species Production Research Articles

Transgenerational intestinal toxicity of 6-PPD quinone in causing ROS production, enhancement in intestinal permeability and suppression in innate immunity in C. elegans

Toxicity of 6-PPD quinone (6-PPDQ) on organisms at various aspects has been frequently observed at parental generation (P0-G). In contrast, we know little about its possible transgenerational toxicity and underlying mechanisms. In Caenorhabditis elegans, exposure to 6-PPDQ (0.1-10μg/L) at P0-G induced transgenerational reactive oxygen species (ROS) production in intestine. Accompanied with this, transgenerational increase in intestinal permeability and decrease in expressions of genes governing intestinal function were observed. Exposure to 6-PPDQ (1 and 10μg/L) at P0-G caused transgenerational suppression in expressions of antimicrobial genes (lys-7 and spp-1) and LYS-7::RFP. Meanwhile, intestinal ROS production could be enhanced by RNAi of acs-22, hmp-2, pkc-3, lys-7, and spp-1. Moreover, acs-22, hmp-2, and pkc-3 RNAi could inhibit innate immune response induced by 6-PPDQ. Additionally, lys-7 and spp-1 RNAi could strengthen intestinal permeability in 6-PPDQ exposed nematodes. Therefore, 6-PPDQ caused transgenerational intestinal toxicity, which was associated with both enhanced intestinal permeability and suppressed innate immunity.

Paeoniflorin alleviates toxicity and accumulation of 6-PPD quinone by activating ACS-22 in Caenorhabditis elegans

6-PPD quinone (6-PPDQ) is extensively existed in various environments. In Caenorhabditis elegans, exposure to 6-PPDQ could cause multiple toxic effects. In the current study, we further used C. elegans to investigate the effect of paeoniflorin (PF) treatment on 6-PPDQ toxicity and accumulation and the underlying mechanism. Treatment with PF (25-100 mg/L) inhibited 6-PPDQ toxicity on reproduction capacity and locomotion behavior and in inducing reactive oxygen species (ROS) production. Additionally, PF (25-100 mg/L) alleviated the dysregulation in expression of genes governing oxidative stress caused by 6-PPDQ exposure. Moreover, PF (25-100 mg/L) inhibited the enhancement in intestinal permeability caused by 6-PPDQ exposure and the accumulation of 6-PPDQ in the body of nematodes. In 6-PPDQ exposed nematodes, PF (25-100 mg/L) increased expression of acs-22 encoding a fatty acid transporter. RNAi of acs-22 could inhibit the beneficial effect of PF against 6-PPDQ toxicity in decreasing reproductive capacity and locomotion behavior, in inducing intestinal ROS production, and in enhancing intestinal permeability. RNAi of acs-22 could also suppress the PF beneficial effect against 6-PPDQ accumulation in the body of nematodes. Therefore, our results demonstrate the function of PF treatment against 6-PPDQ toxicity and accumulation in nematodes by activating the ACS-22.

Aryl hydrocarbon receptor ligands enhance lung immunity through intestinal IKK\u03b2 pathways

BackgroundInfection by antibiotic-resistant microorganisms is common in intensive care units and has become a global problem. Here, we determined the effect of aryl hydrocarbon receptor (AhR) stimulation on antibiotics-induced systemic defense impairment and its mechanisms.MethodsC57BL/6 wild-type (WT) mice received combined antibiotics with or without Ahr ligands (tryptophan and indole), or dead Lactobacillus plantarum supplementation. The defense mechanisms against Pseudomonas aeruginosa infection in the lung were examined.ResultsAntibiotic treatments decreased the phagocytic activity, physiological activity, and the peroxynitrite production of alveolar macrophage (AMs). It also enhanced P. aeruginosa pneumonia-induced bacterial counts in the lung. Tryptophan and dead L. plantarum supplementation reversed antibiotic-induced intracellular adhesion molecule (ICAM) as well as IL-6 expression, and increased P. aeruginosa pneumonia-induced bacterial counts in the lung and increased phagocytic activity and peroxynitrite production of AMs. Moreover, these treatments reversed the antibiotics-induced reduction of Ahr expression, antibacterial proteins, reactive oxygen species (ROS) production, and NF-κB DNA binding activity of the intestinal mucosa and plasma IL-6 levels. P. aeruginosa counts increased and phagocytic activity of AMs and myeloperoxidase (MPO) activity decreased in intestinal IKKβ depleted mice. Antibiotics, antibiotic with tryptophan feeding, or antibiotic with dead L. plantarum feeding treatments did not change the phagocytic activity and peroxynitrite production of AMs, plasma IL-6 levels, and the expression of Ahr of intestine in intestinal IKKβ depleted mice.ConclusionAntibiotic treatment impairs lung immune defenses by decreasing Ahr expression in the intestine and peroyxnitrite production of the AMs. Ahr ligands reverses antibiotic-induced lung defense against bacterial infection through intestinal ROS production and NF-κB activation. The gut is critical in maintaining lung defense mechanism through the intestinal IKKβ pathways.

Biosafety assessment of water samples from Wanzhou watershed of Yangtze Three Gorges Reservoir in the quiet season in Caenorhabditis elegans

We here employed a model animal of Caenorhabditis elegans to perform toxicity assessment of original surface water samples collected from Three Gorges Reservoir (TGR) in the quiet season in Wanzhou, Chongqing. Using some sublethal endpoints, including lifespan, body length, locomotion behavior, brood size, and intestinal reactive oxygen species (ROS) induction, we found that the examined five original surface water samples could not cause toxicity on wild-type nematodes. Nevertheless, the surface water sample collected from backwater area induced the significant increase in expressions of genes (sod-2 and sod-3) encoding Mn-SODs in wild-type nematodes. Among the examined five original surface water samples, exposure to the original surface water sample collected from backwater area could further cause the toxicity in decreasing locomotion behavior and in inducing intestinal ROS production in sod-3 mutant nematodes. Moreover, the solid phase of surface water sample collected from backwater area might mainly contribute to the observed toxicity in sod-3 mutant nematodes. Our results are helpful for understanding the potential effects of surface water in the TGR region in the quiet season on environmental organisms.

Combinational effect of titanium dioxide nanoparticles and nanopolystyrene particles at environmentally relevant concentrations on nematode Caenorhabditis elegans

The possible adverse effects of nanoplastics have received the great attention recently; however, their effects at environmentally relevant concentration on organisms are still largely unclear. We here employed Caenorhabditis elegans to investigate the combinational effects of titanium dioxide nanoparticles (TiO2-NPs) and nanopolystyrene particles at environmentally relevant concentrations on organisms. In wild-type nematodes, prolonged exposure to nanopolystyrene particles (1 μg/L) could enhance the toxicity of TiO2-NPs (1 μg/L) in decreasing locomotion behavior and in inducing intestinal reactive oxygen species (ROS) production. Meanwhile, combinational exposure to TiO2-NPs (1 μg/L) and nanopolystyrene particles (1 μg/L) altered the molecular basis for oxidative stress in wild-type nematodes. Moreover, prolonged exposure to nanopolystyrene particles (0.1 μg/L) could further enhance the toxicity of TiO2-NPs (1 μg/L) in decreasing locomotion behavior and in inducing intestinal ROS production in sod-3 mutant nematodes. Our data suggest the potential role of nanopolystyrene particles at environmentally relevant concentrations in enhancing the toxicity of ENMs in the environment.

A cafeteria diet triggers intestinal inflammation and oxidative stress in obese rats

The gastrointestinal alterations associated with the consumption of an obesogenic diet, such as inflammation, permeability impairment and oxidative stress, have been poorly explored in both diet-induced obesity (DIO) and genetic obesity. The aim of the present study was to examine the impact of an obesogenic diet on the gut health status of DIO rats in comparison with the Zucker (fa/fa) rat leptin receptor-deficient model of genetic obesity over time. For this purpose, female Wistar rats (n 48) were administered a standard or a cafeteria diet (CAF diet) for 12, 14·5 or 17 weeks and were compared with fa/fa Zucker rats fed a standard diet for 10 weeks. Morphometric variables, plasma biochemical parameters, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) levels in the ileum were assessed, as well as the expressions of proinflammatory genes (TNF-α and inducible nitric oxide synthase (iNOS)) and intestinal permeability genes (zonula occludens-1, claudin-1 and occludin). Both the nutritional model and the genetic obesity model showed increased body weight and metabolic alterations at the final time point. An increase in intestinal ROS production and MPO activity was observed in the gastrointestinal tracts of rats fed a CAF diet but not in the genetic obesity model. TNF-α was overexpressed in the ileum of both CAF diet and fa/fa groups, and ileal inflammation was associated with the degree of obesity and metabolic alterations. Interestingly, the 17-week CAF group and the fa/fa rats exhibited alterations in the expressions of permeability genes. Relevantly, in the hyperlipidic refined sugar diet model of obesity, the responses to chronic energy overload led to time-dependent increases in gut inflammation and oxidative stress.

Beneficial effects of Glycyrrhizae radix extract in preventing oxidative damage and extending the lifespan of Caenorhabditis elegans

Glycyrrhizae radix (GR) is a medicinal herb extensively used in traditional Chinese medicine. This study aimed to evaluate the pharmacological effect of GR and the possible mechanisms of GR, to provide a pharmacological basis in traditional medicine. In the present study, C. elegans (L1-larvae to young adults) was exposed to 0.12-0.24 g/mL of GR in 12-well sterile tissue culture plates at 20°C in the presence of food. Lethality, growth, lifespan, reproduction, locomotion, metabolism, intestinal autofluorescence, and reactive oxygen species (ROS) production assays were performed to investigate the possible safety profile and beneficial effects of GR in these nematodes. We found that the lifespan of nematodes exposed to 0.18-0.24 g/mL of GR was extended. We then determined the mechanism of the longevity effect of GR using quantitative reverse transcription PCR and oxidative stress resistance assays induced by heat and paraquat. Prolonged exposure to 0.12-0.24 g/mL of GR did not induce lethality, alter body length, morphology or metabolism, affect brood size, locomotion, the development of D-type GABAergic motor neurons, or induce significant induction of intestinal autofluorescence and intestinal ROS production. In C. elegans, pretreatment with GR suppressed the damage due to heat-stress or oxidative stress induced by paraquat, a ROS generator, on lifespan, and inhibited the induction of intestinal ROS production induced by paraquat. Moreover, prolonged exposure to GR extended lifespan, increased locomotion and decreased intestinal ROS production in adult day-12 nematodes. Furthermore, prolonged exposure to GR significantly altered the expression patterns of genes encoding the insulin-like signaling pathway which had a key role in longevity control. Mutation of daf-16 gene encoding the FOXO transcription factor significantly decreased lifespan, suppressed locomotion, and increased intestinal ROS production in GR exposed adult nematodes. GR is relatively safe and has protective effects against the damage caused by both heat-stress and oxidative stress at the examined concentrations. Furthermore, GR is capable of extending the lifespan of nematodes, and the insulin-like signaling pathway may play a crucial role in regulating the lifespan-extending effects of GR.

Increasing intestinal reactive oxygen species reverses diabetes-induced inflammation (MUC2P.928)

Abstract Systemic inflammation appears to persist in diabetic patient. To examine the role of reactive oxygen species (ROS) of intestine in DM-induced inflammation, streptozotocin (STZ)-induced diabetes and Ins2Akita (Ins2Akita mutation mutant) mice were used. STZ mice demonstrated a significant decrease of Lacobacilli as well as ROS production and a marked increase of p-JNK as well as iNOS expression in the intestinal mucosa. Oral supplementation of fructooligosaccharides (FOS) or dead Lacobacilli increased the production of ROS of intestine and decreased IL-1β expression of Kupffer cells in STZ and Ins2Akita mice. Feeding of L-NAME, an iNOS inhibitor, but not D-NAME increased the production of ROS of intestinal mucosa and decreased endotoxin in portal vein and IL-1β expression of Kupffer cells in STZ mice. Oral feeding of N-Acetylcysteine, a ROS scavenger, decreased ROS production and inhibited the effects of FOS as well as L-NAME on reversing DM-induced ICAM expression of liver. Using STZ JNK1-/- and Ins2Akita JNK1-/- mice to reverse DM-induced pJNK expression of intestinal mucosa induced a significant decrease of IL-1β expression of Kupffer cells and ICAM expression of liver. Collectively, diabetes induces systemic inflammation through decreasing ROS production and increasing pJNK expression of intestine. Increasing intestinal ROS production could reverse diabetes-induced systemic inflammation.

Beneficial Effects of Wheat Gluten Hydrolysate to Extend Lifespan and Induce Stress Resistance in Nematode Caenorhabditis elegans

Previous studies have showed that wheat gluten hydrolysate (WGH) has the anti-oxidative property. In the present study, we examined the possible safety property of WGH and the beneficial effects of WGH to extend lifespan and induce stress resistance using nematode Caenorhabditis elegans as the in vivo assay system. We found that WGH at concentrations of 0.1–1 mg/mL did not cause lethality, influence development, alter locomotion behavior and brood size, and induce significant intestinal autofluorescence and reactive oxygen species (ROS) production in young adults. Treatment with 0.1–1 mg/mL of WGH significantly extended lifespans of nematodes under the normal conditions. Moreover, WGH treatment significantly inhibited the induction of intestinal autofluorescence and suppressed the decrease in locomotion behavior during the aging process of nematodes. Furthermore, pre-treatment with 1 mg/mL of WGH significantly suppressed the adverse effects caused by heat-stress or oxidative stress on nematodes as indicated by the alterations of both lifespan and intestinal ROS production. Therefore, WGH treatment is relatively safe and has beneficial effects on nematodes under both the normal conditions and the stress conditions.

Positive Role of CCAAT/Enhancer-Binding Protein Homologous Protein, a Transcription Factor Involved in the Endoplasmic Reticulum Stress Response in the Development of Colitis

Although recent reports suggest that the endoplasmic reticulum (ER) stress response is induced in association with the development of inflammatory bowel disease, its role in the pathogenesis of inflammatory bowel disease remains unclear. The CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is a transcription factor that is involved in the ER stress response, especially ER stress-induced apoptosis. In this study, we found that experimental colitis was ameliorated in CHOP-null mice, suggesting that CHOP exacerbates the development of colitis. The mRNA expression of Mac-1 (CD11b, a positive regulator of macrophage infiltration), Ero-1alpha, and Caspase-11 (a positive regulator of interleukin-1beta production) in the intestine was induced with the development of colitis, and this induction was suppressed in CHOP-null mice. ERO-1alpha is involved in the production of reactive oxygen species (ROS); an increase in ROS production, which is associated with the development of colitis in the intestine, was suppressed in CHOP-null mice. A greater number of apoptotic cells in the intestinal mucosa of wild-type mice were observed to accompany the development of colitis compared with CHOP-null mice, suggesting that up-regulation of CHOP expression exacerbates the development of colitis. Furthermore, this CHOP activity appears to involve various stimulatory mechanisms, such as macrophage infiltration via the induction of Mac-1, ROS production via the induction of ERO-1alpha, interleukin-1beta production via the induction of Caspase-11, and intestinal mucosal cell apoptosis.