Intestinal Toxicity Research Articles

Measurement of an intestinal biomarker during poisonings from select toxicants and toxins

Introduction Intestinal toxicity can occur following ingestion of various drugs, chemicals, and toxins. Intestinal fatty acid binding protein is a cytosolic protein specific to intestinal epithelial cells released into the systemic circulation following intestinal injury. Understanding intestinal toxicity in poisoning has the potential to explain mechanisms of toxicity and gastrointestinal symptoms. Methods Plasma samples were retrospectively analysed for intestinal fatty acid binding protein in 25 healthy controls and in those poisoned with Gloriosa superba (n = 18), Thevetia peruviana (n = 26), organophosphates (in various solvents) (n = 17), paracetamol (n = 14), glyphosate (n = 20), 2-methyl-4-chlorophenoxyacetic acid (n = 18) and propanil (n = 19). Results Median peak plasma intestinal fatty acid binding protein concentrations were significantly higher in patients poisoned with Gloriosa superba (2,994.1 µg/L; interquartile range 600.0–5,158.2, P < 0.001), Thevetia peruviana (1,292.5 µg/L; interquartile range 760.3 − 2,076.2; P < 0.001), glyphosate (1,803.6 µg/L; interquartile range 225.7–8,927.7; P < 0.001), 2-methyl-4-chlorophenoxyacetic acid (1,236.2 µg/L; interquartile range 192.6 − 1,709.7; P = 0.010), paracetamol (1,066.5 µg/L; interquartile range 512.9 − 1,336.9; P = 0.035), and organophosphate poisoning (729.8 µg/L; interquartile range 431.5 − 1,588.2; P = 0.046) than in healthy controls (221.6 µg/L; interquartile range 134.8 − 460.1). Median intestinal fatty acid binding protein was not statistically significantly increased compared to controls after propanil poisoning (630.0 µg/L; interquartile range 23.5 − 1,390.3; P = 0.423). Conclusions Our pilot study describes intestinal injury assessed by elevated plasma intestinal fatty acid binding protein concentrations following the ingestion of several poisons. This serves as a foundation for further exploration into enterocyte damage in toxicology.

Q-marker prediction of resin ethanol extract of Gegen Qinlian Decoction based on characteristic spectrum and network pharmacology

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the &quot;five principles&quot; of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.

ARTIA-Cervix: A prospective clinical trial to assess patient reported intestinal toxicity with adaptive external beam radiation therapy in the treatment of cervical cancer (1277)

ARTIA-Cervix: A prospective clinical trial to assess patient reported intestinal toxicity with adaptive external beam radiation therapy in the treatment of cervical cancer (1277)

Characterization and Stability of a Novel Toxin in Scallop Mantle Tissue.

Previous studies have shown that mice fed a diet containing 1% mantle tissue exhibited decreased food consumption and led to death. Toxic substances present in the mantle tissue have been isolated and identified. In the present study, we explored the characteristics and stability of mantle tissue toxicity. The treatment of mantle tissue with 1 mM hydrochloric acid, 1 mM sodium hydroxide, 1 mM dithiothreitol, and 1 mM hydrogen peroxide followed by heating did not significantly reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic conditions and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Mice fed a diet containing 20% mantle tissue did not show a distinct increase in toxicity compared with mice fed a diet containing 1% mantle tissue, demonstrating that feeding mantle tissue does not lead to acute toxicity. Finally, mantle tissue toxicity in the small intestine was examined. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time polymerase chain reaction analysis revealed that mantle tissue feeding caused changes in inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that mantle tissue feeding causes toxicity after initial damage to the small intestinal tissue.

Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade.

F. prausnitzii alleviates colitis while enhancing the tumor-suppressive effects of immune checkpoint blockade, indicating that supplementation with F. prausnitzii could be a treatment strategy to mitigate immunotherapy toxicity in patients with cancer.

Melatonin alleviates 3,3',4,4',5-pentachlorobenzene induced colon injury by relieving oxidative stress.

3,3',4,4',5-pentachlorobiphenyl (PCB126) is widely distributed, non-degradable and bioaccumulative, which can affect the function of tissues and organs of the living organisms. Melatonin (MT) is a sort of indole neurohormone that is mainly secreted by the pineal gland. Numerous studies have shown that MT can alleviate intestinal injury through various mechanisms such as antioxidant, anti-inflammatory, and anti-apoptosis. For the above reasons, the aim of this study is to explore the mechanism of intestinal injury in mice after exposure to PCB126 as well as the antagonistic effect of MT. Mice were respectively fed PCB126 (0.326 mg/kg) and/or MT (10 mg/kg) in vivo. In vitro, colonic epithelial cells (MCEC) were treated with PCB126 (150 μM) and/or MT (2 mM). We found that the microscopic structure of colon tissue was impaired after exposure to PCB126. The levels of oxidative stress, the protein and mRNA levels of expression of inflammatory related factors were significantly increased and the expression levels of intestinal tight junction protein were decreased. Notably, MT can promote Nrf2/HO-1 expression level and reduce the colonic injury caused by PCB126. Further in vitro treatment with reactive oxygen species inhibitors (NAC) showed that it significantly alleviated PCB126-induced in MCEC cell damage. In summary, the above results suggested that MT alleviates PCB126-induced colon inflammation by inhibiting the overproduction of reactive oxygen species (ROS) and up-regulating the expression level of intestinal tight junction protein. Our results contribute to the further comprehension of the intestinal toxicity effects of PCB126 and the significant role of MT in preserving the mechanisms of intestinal injury.

Comparison of salvage high dose-rate brachytherapy and external beam radiotherapy for treatment of prostate cancer local recurrence after radical prostatectomy

Aim. To compare clinical efficacy of salvage high dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBR) in treatment of local recurrence of prostate cancer after radical prostatectomy (RP).Materials and methods. Between January 2017 and December 2020, 60 patients with local recurrence of prostate cancer after RP were treated at the Russian Scientific Center of Roentgenology and Radiology. Two groups were identified: group 1 included 30 patients who underwent salvage external beam radiation therapy (EBRT) according to the classical fractionation regimen; in group 2, within the framework of the scientific protocol, 30 patients underwent 2 fractions of salvage HDR-BT with single boost dose of 15 Gy for total boost dose of 30 Gy. All patients in group 2 underwent pelvic multiparametric magnetic resonance imaging and positron emission tomography-computed tomography with prostatespecific membrane antigen ligands. In the 2nd group, transrectal biopsy of the prostate bed was also performed. Overall and biochemical recurrence-free survival, as well as the profile of early and late radiation complications, were analyzed.Results. Mean age of the patients at the time of salvage radiation therapy was 67.5 years (95 % confidence interval 66.1–69). Median time before development of biochemical relapse after RP was 24 months (interquartile range 13–46 months). Median follow-up period for all patients was 45 months (interquartile range 36–63 months). There were no dropouts in this study. The overall survival rate was 100 % in both groups. Comparative analysis of prostate specific antigen (PSA)-specific recurrence-free survival showed a clear trend toward an increase in the brachytherapy group; however, with the number of observations, statistically significant differences could not be achieved (p = 0.075). Salvage EBRT is more toxic than salvage HDR-BT. Comparative assessment of radiation adverse effects revealed higher frequency of early genitourinary toxicity of grade I and intestinal toxicity of grades I and II in the salvage EBRT group than in the salvage brachytherapy group, as well as late gastrointestinal toxicity of grade I and II.Conclusion. Salvage HDR-BT with 15 Gy × 2 fractions with total boost dose of up to 30 Gy was proved to be a promising treatment for local recurrence of prostate cancer after RP with an acceptable toxicity profile. There was also a trend towards increased PSA-specific recurrence-free survival in the salvage brachytherapy group compared with the salvage EBRT group.

Vinpocetine mitigates methotrexate-induced duodenal intoxication by modulating NF-κB, JAK1/STAT-3, and RIPK1/RIPK3/MLKL signals

Objectives Methotrexate (MTX) is an antimetabolite agent widely used to manage a variety of tumors and autoimmune diseases. Nonetheless, MTX-induced intestinal intoxication is a serious adverse effect limiting its clinical utility. Inflammation and oxidative stress are possible mechanisms for MTX-induced intestinal toxicity. Vinpocetine (VNP) is a derivative of the alkaloid vincamine with potent anti-inflammatory and antioxidant effects. The current study investigated the protective intestinal impact of VNP in attenuating MTX-induced intestinal intoxication in rats. Materials and Methods VNP was administered orally in a dose of 20 mg/kg, while MTX was injected intraperitoneal in a dose of 20 mg/kg. Results VNP administration attenuated drastic histological changes induced by MTX and preserved both normal villus and crypt histology. VNP significantly attenuated oxidative injury by upregulating intestinal Nrf2 and HO-1 expression. VNP attenuated inflammation by reducing MPO, NO2 −, TNF-α, and IL-1β levels mediated by downregulating NF-κB, NDAPH-oxidase, IRF3, p-JAK-1, and p-STAT-3 expressions. Moreover, VNP potently counteracted intestinal necroptosis by effectively downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins. Conclusion Therefore, VNP may represent a promising approach that can attenuate intestinal toxicity in patients receiving MTX.

Combined Effects of Micro- and Nanoplastics at the Predicted Environmental Concentration on Functional State of Intestinal Barrier in Caenorhabditis elegans.

The possible toxicity caused by nanoplastics or microplastics on organisms has been extensively studied. However, the unavoidably combined effects of nanoplastics and microplastics on organisms, particularly intestinal toxicity, are rarely clear. Here, we employed Caenorhabditis elegans to investigate the combined effects of PS-50 (50 nm nanopolystyrene) and PS-500 (500 nm micropolystyrene) at environmentally relevant concentrations on the functional state of the intestinal barrier. Environmentally, after long-term treatment (4.5 days), coexposure to PS-50 (10 and 15 μg/L) and PS-500 (1 μg/L) resulted in more severe formation of toxicity in decreasing locomotion behavior, in inhibiting brood size, in inducing intestinal ROS production, and in inducting intestinal autofluorescence production, compared with single-exposure to PS-50 (10 and 15 μg/L) or PS-500 (1 μg/L). Additionally, coexposure to PS-50 (15 μg/L) and PS-500 (1 μg/L) remarkably caused an enhancement in intestinal permeability, but no detectable abnormality of intestinal morphology was observed in wild-type nematodes. Lastly, the downregulation of acs-22 or erm-1 expression and the upregulation expressions of genes required for controlling oxidative stress (sod-2, sod-3, isp-1, clk-1, gas-1, and ctl-3) served as a molecular basis to strongly explain the formation of intestinal toxicity caused by coexposure to PS-50 (15 μg/L) and PS-500 (1 μg/L). Our results suggested that combined exposure to microplastics and nanoplastics at the predicted environmental concentration causes intestinal toxicity by affecting the functional state of the intestinal barrier in organisms.

A Review on the Uptake, Accumulation, Impact and Determinants of Microcystins on Intestinal Health

Microcystins (MCs) released during cyanobacterial blooms induce immense toxic manifestations in animals and humans. The International Agency for Research on Cancer (IARC) categorized MC as a possible carcinogen. Research indicates that aside from the liver, MCs can negatively impact the intestine. Interestingly, less attention exists with respect to MCs effects on the intestine in spite of the organ being the focal site of the toxins’ uptake. Compiling data from in vivo and in vitro studies, the current review summarized available literature on the impact of MCs on intestinal health. In addition, the toxins’ uptake, accumulation, and various methods used to determine intestinal toxicity were elucidated.

MiR-155-5p Elevated by Ochratoxin A Induces Intestinal Fibrosis and Epithelial-to-Mesenchymal Transition through TGF-β Regulated Signaling Pathway In Vitro and In Vivo.

Ochratoxin A (OTA) is a mycotoxin that induces fibrosis and epithelial-to-mesenchymal transitions (EMT) in kidneys and livers. It enters our bodies through food consumption, where it is absorbed in the intestines. However, the impact of OTA on the intestines is yet to be studied. MicroRNA (miRNAs) are small non-coding single-stranded RNAs that block the transcription of specific mRNAs and are, therefore, involved in many biochemical processes. Our findings indicate that OTA can induce EMT and intestinal fibrosis both in vivo and in vitro. This study examines the impact of OTA on intestinal toxicity and the role of miRNAs in this process. Following OTA treatment, miR-155-5p was the most elevated miRNA by next-generation sequencing. Our research showed that OTA increased miR-155-5p levels through transforming growth factor β (TGF-β), leading to the development of intestinal fibrosis and EMT. Additionally, the study identified that the modulation of TGF-β and miR-155-5p by OTA is linked to the inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and Smad2/3 accumulation in the progression of intestinal fibrosis.

RadioTransNet, Radiotherapy Translational and Preclinical Research Network: Results from the dedicated French cancer institute (INCa) call for projects

PurposeThe RadioTransNet project is a French initiative structuring preclinical and translational research in radiation therapy for cancer at national level. The network's activities are organized around four chosen priorities, which are: target definition, normal tissue, combined treatments and dose modelling. The subtargets linked to these four major priorities are unlimited. They include all aspects associated with fundamental radiobiology, preclinical studies, imaging, medical physics research and transversal components clearly related to these scientific areas, such as medical oncology, radio-diagnostics, nuclear medicine and cost-effectiveness considerations. MethodDuring its first phase of activity, four workshops following the consensus conference model and based on scientific and medical state of the art in radiotherapy and radiobiology were organized on the four above-mentioned objectives to identify key points. Then a road map has been defined and served as the basis for the opening in 2022 of a dedicated call, SEQ-RTH22, proposed by the French cancer national institute (INCa). ResultsFour research projects submitted by RadioTransNet partners have been selected to be supported by INCa: the first by Professor Anne Laprie from Oncopole Claudius-Regaud and Inserm ToNic in Toulouse on neurocognition and health after pediatric irradiation, the second submitted by Fabien Milliat from IRSN aims to study decryption and targeting of endothelial cell–immune cells interactions to limit radiation-induced intestinal toxicity, the third project, submitted by Yolanda Prezado from institut Curie–CNRS on proton minibeam radiotherapy as a new approach to reduce toxicity, and the latest project proposed by R. de Crevoisier from centre Eugène-Marquis in Rennes on predictive multiscale models of head and neck radiotoxicity induced for optimized personalized radiation therapy. Topics of each of these projects are presented here. ConclusionRadioTransNet project has been launched in 2018, supported by INCa, in order to structure and promote preclinical research in oncology radiotherapy and to favor collaboration between the actors of this research. INCa relied on RadioTransNet initiatives and activities, resulting in the opening of dedicated call for projects. Beyond its first main goals, RadioTransNet network is able to help to fund the human and technical resources necessary to conduct optimal translational and preclinical research in radiation oncology.

Marasmius androsaceus mitigates depression-exacerbated intestinal radiation injuries through reprogramming hippocampal miRNA expression

IntroductionCancer patients commonly experience high levels of psychological stress, which poses significant risks to their well-being. Radiotherapy is a primary treatment modality for cancer; however, it often leads to intestinal injuries in these patients. Nevertheless, the impact of mental stress on radiotherapy-intertwined complications remains unclear. MethodsTo induce intestinal injury, we employed total abdominal irradiation in our experimental model. We conducted high-throughput sequencing to analyze the expression profile of miRNAs in the hippocampus. ResultsWe observed that mice with depression exhibited more severe intestinal injuries following total abdominal irradiation. Remarkably, oral administration of Marasmius androsaceus not only alleviated the depressive phenotype but also mitigated radiation-induced intestinal toxicity. Notably, this radioprotective effect was not observed in mice without depression. Depression disrupted the hippocampal miRNA expression profile in mice subjected to local irradiation of the abdomen, leading to the accumulation of miR-139–5p and miR-184–3p in the hippocampus, serum, and small intestine tissues. However, treatment with Marasmius androsaceus reprogrammed the miRNA expression signature in mice with depression. Furthermore, intravenous injection of antagomirs targeting miR-139–5p and miR-184–3p ameliorated depression, up-regulated Spn expression, reduced radiation enteritis, and improved the integrity of the small intestine in irradiated mice. ConclusionOur findings demonstrate the efficacy of Marasmius androsaceus, a small mushroom, in alleviating depression-aggravated intestinal toxicity following radiotherapy by reprogramming hippocampal miRNA expression.

Arsenic exposure induces small intestinal toxicity in mice by barrier damage and inflammation response via activating RhoA/ROCK and TLR4/Myd88/NF-κB signaling pathways

Numerous studies have shown that arsenic (As) is an important hazardous metalloid that is commonly considered to have systemic toxicity. The main pathway of arsenic exposure is oral; however, many of the events that occur during its passage through the gastrointestinal tract are unclear, and there are few reports on the effect of arsenic on small intestinal mucosal barrier. This study aimed to investigate arsenic-induced mucosal barrier damage in the small intestine of mice induced by oral exposure and its potential mechanisms. In the present study, histomorphometric and immunohistochemical analyses showed that arsenic-treated mice exhibited signs of irregularly arranged and atrophied small intestinal villi, reduced villus lengths, inflammatory cells infiltration, along with up-regulated expression of inflammatory factors TNF-α, IL-6 and IL-1β in the small intestine of mice. The myeloperoxidase (MPO) activity was also increased in As-exposed mice. Transmission electron microscopy (TEM) analysis demonstrated that intestinal epithelial tight junctions (TJs) were impaired in the small intestines of mice in As group. In addition, arsenic down-regulated mRNA levels of TJ-related genes (ZO-1, ZO-2, occludin, claudin-1, and claudin-7) and protein levels of ZO-1, occludin and claudin-1 were significantly reduced in arsenic-treated groups, while arsenic also increased levels of TLR4, Myd88, NF-κB, RhoA, and ROCK mRNA and protein expression. In summary, these results indicate that the small intestine toxicity in mice evoked by arsenic was correlated with the activation of TLR4/Myd88/NF-κB and RhoA/ROCK pathways.

Copper induced intestinal inflammation response through oxidative stress induced endoplasmic reticulum stress in Takifugu fasciatus

Copper (Cu) pollution in aquaculture water has seriously threatened the healthy and sustainable development of the aquaculture industry. Recently, many researchers have studied the toxic effects of Cu exposure on fish. However, the relationship between endoplasmic reticulum stress (ERS) and the inflammatory response, as well as its possible mechanisms, remain unclear. Particularly, information related to fish intestines must be expanded. Our study initially investigated the mechanisms underlying intestinal toxicity and inflammation resulting from Cu-induced ERS in vivo and in vitro in Takifugu fasciatus. In vivo study, T. fasciatus were treated with different concentrations (control, 20, and 100 µg/L) of Cu exposure for 28 days, causing intestinal oxidative stress, ERS, inflammatory responses, and histopathological and ultrastructural damage. Transcriptomic data further showed that Cu exposure caused ERS, as well as inflammatory responses, in the intestinal tracts of T. fasciatus. In vitro experiments on the intestinal cells of T. fasciatus showed that Cu exposure treatment (7.5 µg/mL) for 24 h induced ERS and increased mitochondrial numbers and inflammatory responses. In contrast, the addition of 4-phenylbutyric acid (4-PBA) alleviated ERS and inflammatory response in the Cu-exposed group. Furthermore, the reactive oxygen species (ROS) inhibitor, N-Acetyl-l-cysteine (NAC), effectively alleviated Cu-induced ERS. In conclusion, our in vivo and in vitro studies have confirmed that oxidative stress triggers the ERS pathway, which is involved in the intestinal inflammatory response. Our study provides new insights into the relationship among Cu-induced oxidative stress, ERS, and inflammatory responses in fish, as well as for the healthy culture of fish in aqueous environments.

Effects of triclosan adsorption on intestinal toxicity and resistance gene expression in Xenopus tropicalis with different particle sizes of polystyrene

Microplastics (MPs) are commonly found with hydrophobic contaminants in the water column and pose a serious threat to aquatic organisms. The effects of polystyrene microplastics of different particle sizes on the accumulation of triclosan in the gut of Xenopus tropicalis, its toxic effects, and the transmission of resistance genes were evaluated. The results showed that co-exposure to polystyrene (PS-MPs) adsorbed with triclosan (TCS) caused the accumulation of triclosan in the intestine with the following accumulation capacity: TCS + 5 µm PS group > TCS group > TCS + 20 µm PS group > TCS + 0.1 µm PS group. All experimental groups showed increased intestinal inflammation and antioxidant enzyme activity after 28 days of exposure to PS-MPs and TCS of different particle sizes. The TCS + 20 µm PS group exhibited the highest upregulated expression of pro-inflammatory factors (IL-10, IL-1β). The TCS + 20 µm group showed the highest increase in enzyme activity compared to the control group. PS-MPs and TCS, either alone or together, altered the composition of the intestinal microbial community. In addition, the presence of more antibiotic resistance genes than triclosan resistance genes significantly increased the expression of tetracycline resistance and sulfonamide resistance genes, which may be associated with the development of intestinal inflammation and oxidative stress. This study refines the aquatic ecotoxicity assessment of TCS adsorbed by MPs and provides informative information for the management and control of microplastics and non-antibiotic bacterial inhibitors.

Zinc and L-carnitine combination with or without methotrexate prevents intestinal toxicity during arthritis treatment via Nrf2/Sirt1/Foxo3 pathways: an In vivo and molecular docking approach.

Methotrexate (MTX) is an antifolate that is inescapable and widely used to treat autoimmune diseases and is the gold standard medicine for the arthritic condition. Despite its importance, it is more prone to gastrointestinal toxicity, which is most common in arthritis patients during MTX treatment. Combination therapies are required to ensure MTX's antiarthritic activity while providing gastrointestinal protection. Zinc (Zn) and L-carnitine (Lc) are well-known potent antioxidants and anti-inflammatory supplements with promising results in pre-clinical studies. Arthritis was induced in Wistar rat's ankles with Freund's adjuvant and treated with either MTX (2.5mg/kg b.w per week for two weeks) or Zn (18mg/kg b.w. per day) Lc (200mg/kg b.w. per day) individually or in combination (MTX + Zn Lc). The antiarthritic effects were evaluated by body weight, paw volume, ankle tissue, and joint histopathology. At the same time, anti-toxicity/gastrointestinal protective activity was examined by tissue oxidative stress markers, antioxidants, mitochondrial function, inflammatory mediators, and antioxidant signaling proteins and their binding mechanism. Repercussions of MTX intoxication induced upregulation of oxidative stress markers, antioxidant depletion, ATP depletion, decreased expression of Nrf2/Sirt1/Foxo3, and the overexpression of inflammatory mediators attenuated by co-treatment with Zn Lc. Zn Lc markedly mitigated MTX-instigated intestinal injury by activating antioxidant signaling mechanisms Nrf2/Sirt1/Foxo3 signaling and tissue architectural anomalies and exhibited an enhanced antiarthritic effect. In conclusion, we report that Zn Lc and MTX combination could presumably protect the intestine from low-dose MTX which managed arthritis but induced severe intestinal damage with increased inflammation and downregulated Nrf2/Sirt1/Foxo3 pathway.

Single and combined effects of polyethylene microplastics and acetochlor on accumulation and intestinal toxicity of zebrafish (Danio rerio)

The co-exposure of microplastics (MPs) and other contaminants has aroused extensive attention, but the combined impacts of MPs and pesticides remain poorly understood. Acetochlor (ACT), a widely used chloroacetamide herbicide, has raised concerns for its potential bio-adverse effects. This study evaluated the influences of polyethylene microplastics (PE-MPs) for acute toxicity, bioaccumulation, and intestinal toxicity in zebrafish to ACT. We found that PE-MPs significantly enhanced ACT acute toxicity. Also, PE-MPs increased the accumulation of ACT in zebrafish and aggravate the oxidative stress damage of ACT in intestines. Exposure to PE-MPs or/and ACT causes mild damage to the gut tissue of zebrafish and altered gut microbial composition. In terms of gene transcription, ACT exposure triggered a significant increase in inflammatory response-related gene expressions in the intestines, while some pro-inflammatory factors were found to be inhibited by PE-MPs. This study provides a new perspective on the fate of MPs in the environment and on the assessment of the combined effects of MPs and pesticides on organisms.

Carvacrol, sodyum arsenit kaynaklı ince bağırsak toksisitesini iyileştirmektedir

Arsenic is a very dangerous metal that is widely distributed in the environment as a result of anthropogenic and natural processes. On the other hand, it is thought that treatment with natural flavonoids may protect against arsenic toxicity. Carvacrol (CRV) is a naturally occurring phenolic compound with anti-inflammatory, anti-apoptotic, and antioxidant properties. This study aims to investigate the protective effects of CRV on sodium arsenite (SA)-induced intestinal toxicity. For this purpose, rats were randomly divided into five groups and administered SA and CRV orally for 14 days. The data indicate that when SA is administered, lipid peroxidation increase and antioxidant enzyme activities decrease. The administration of CRV ameliorated this impairment in the antioxidant defense system. Examining the expression levels of NF-kB and IL-1 revealed that inflammation increased with SA application but decreased with CRV administration. Moreover, the expression levels of Caspase-3 and Apaf1 increased in rats treated with SA, whereas the severity of apoptosis decreased when CRV was administered. In light of these findings, it is possible to state that CRV protects tissues from damage by presenting antioxidant, anti-inflammatory, and anti-apoptotic effects in SA-induced intestinal toxicity.

Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study

BackgroundRecent evidences highlight role of mitochondria in the development of 5-fluorouracil (5-FU)-induced intestinal toxicity. Mitochondria-targeted antioxidants are well-known for their protective effects in mitochondrial oxidative stress- mediated diseases. In the present study, we investigated protective effect of Mito-TEMPO in 5-FU-induced intestinal toxicity.MethodsMito-TEMPO (0.1 mg/kg b.w.) was administered intraperitoneally to male BALB/c mice for 7 days, followed by co-administration of 5-FU for next 4 days (intraperitoneal 12 mg/kg b.w.). Protective effect of Mito-TEMPO on intestinal toxicity was assessed in terms of histopathological alterations, modulation in inflammatory markers, apoptotic cell death, expression of 8-OhDG, mitochondrial functional status and oxidative stress.Results5-FU administered animals showed altered intestinal histoarchitecture wherein a shortening and atrophy of the villi was observed. The crypts were disorganized and inflammatory cell infiltration was noted. Mito-TEMPO pre-protected animals demonstrated improved histoarchitecture with normalization of villus height, better organized crypts and reduced inflammatory cell infiltration. The inflammatory markers and myeloperoxidase activity were normalized in mito-TEMPO protected group. A significant reduction in intestinal apoptotic cell death and expression of 8-OhDG was also observed in mito-TEMPO group as compared to 5-FU group. Further, mtROS, mtLPO and mitochondrial antioxidant defense status were improved by mito-TEMPO.ConclusionMito-TEMPO exerted significant protective effect against 5-FU-induced intestinal toxicity. Therefore, it may be used as an adjuvant in 5-FU chemotherapy.