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Probiotics, prebiotics, and synbiotics to prevent or combat air pollution consequences: The gut-lung axis
2022
Keulers, Loret | Dehghani, Ali | Knippels, Leon | Garssen, J. | Papadopoulos, Nikolaos | Folkerts, Gert | Braber, Saskia | van Bergenhenegouwen, Jeroen
Air pollution exposure is a public health emergency, which attributes globally to an estimated seven million deaths on a yearly basis We are all exposed to air pollutants, varying from ambient air pollution hanging over cities to dust inside the home. It is a mixture of airborne particulate matter and gases that can be subdivided into three categories based on particle diameter. The smallest category called PM₀.₁ is the most abundant. A fraction of the particles included in this category might enter the blood stream spreading to other parts of the body. As air pollutants can enter the body via the lungs and gut, growing evidence links its exposure to gastrointestinal and respiratory impairments and diseases, like asthma, rhinitis, respiratory tract infections, Crohn's disease, ulcerative colitis, and abdominal pain. It has become evident that there exists a crosstalk between the respiratory and gastrointestinal tracts, commonly referred to as the gut-lung axis. Via microbial secretions, metabolites, immune mediators and lipid profiles, these two separate organ systems can influence each other. Well-known immunomodulators and gut health stimulators are probiotics, prebiotics, together called synbiotics. They might combat air pollution-induced systemic inflammation and oxidative stress by optimizing the microbiota composition and microbial metabolites, thereby stimulating anti-inflammatory pathways and strengthening mucosal and epithelial barriers. Although clinical studies investigating the role of probiotics, prebiotics, and synbiotics in an air pollution setting are lacking, these interventions show promising health promoting effects by affecting the gastrointestinal- and respiratory tract. This review summarizes the current data on how air pollution can affect the gut-lung axis and might impact gut and lung health. It will further elaborate on the potential role of probiotics, prebiotics and synbiotics on the gut-lung axis, and gut and lung health.
اظهر المزيد [+] اقل [-]Development of physiologically-based toxicokinetic-toxicodynamic (PBTK-TD) model for 4-nonylphenol (4-NP) reflecting physiological changes according to age in males: Application as a new risk assessment tool with a focus on toxicodynamics
2022
Jeong, Seung-Hyun | Jang, Ji-Hun | Lee, Yong-Bok
Environmental exposure to 4-nonylphenol (4-NP) is extensive, and studies related to human risk assessment must continue. Especially, prediction of toxicodynamics (TDs) related to reproductive toxicity in males is very important in risk-level assessment and management of 4-NP. This study aimed to develop a physiologically-based-toxicokinetic-toxicodynamic (PBTK-TD) model that added a TD prostate model to the previously reported 4-n-nonylphenol (4-n-NP) physiologically-based-pharmacokinetic (PBPK) model. Modeling was performed under the assumption of similar TKs between 4-n-NP and 4-NP because TK experiments on 4-NP, a random-mixture, are practically difficult. This study was very important to quantitatively predict the TKs and TDs of 4-NP by age at exposure using an advanced PBTK-TD model that reflected physiological-changes according to age. TD-modeling was performed based on the reported toxic effects of 4-NP on RWPE-1 cells, a human-prostate-epithelial-cell-line. Through a meta-analysis of reported human physiological data, body weight, tissue volume, and blood flow rate patterns according to age were mathematically modeled. These relationships were reflected in the PBTK-TD model for 4-NP so that the 4-NP TK and TD changes according to age and their differences could be confirmed. Differences in TK and TD parameters of 4-NP at various ages were not large, within 3.61-fold. Point-of-departure (POD) and reference-doses for each age estimated using the model varied as 426.37–795.24 and 42.64–79.52 μg/kg/day, but the differences (in POD or reference doses between ages) were not large, at less than 1.87-times. The PBTK-TD model simulation predicted that even a 100-fold 4-NP PODₘₐₙ dose would not have large toxicity to the prostate. With a focus on TDs, the predicted maximum possible exposure of 4-NP was as high as 6.06–23.60 mg/kg/day. Several toxicity-related values estimated by the dose-response curve were higher than those calculated, depending upon the PK or TK, which would be useful as a new exposure limit for prostate toxicity of 4-NP.
اظهر المزيد [+] اقل [-]Toxicokinetics and systematic responses of differently sized indium tin oxide (ITO) particles in mice via oropharyngeal aspiration exposure
2021
Qu, Jing | Wang, Jianli | Zhang, Haopeng | Wu, Jingying | Ma, Xinmo | Wang, Shile | Zang, Yiteng | Huang, Yuhui | Ma, Ying | Cao, Yuna | Wu, Daming | Zhang, Ting
Indium tin oxide (ITO) is an important semiconductor material, because of increasing commercial products consumption and potentially exposed workers worldwide. So, urgently we need to assess and manage potential health risks of ITO. Although the Occupational Exposure Limit (OEL) has been established for ITO exposure, there is still a lack of distinguishing the risks of exposure to particles of different sizes. Therefore, obtaining toxicological data of small-sized particles will help to improve its risk assessment data. Important questions raised in quantitative risk assessments for ITO particles are whether biodistribution of ITO particles is affected by particle size and to what extent systematic adverse responses is subsequently initiated. In order to determine whether this toxicological paradigm for size is relevant in ITO toxic effect, we performed comparative studies on the toxicokinetics and sub-acute toxicity test of ITO in mice. The results indicate both sized-ITO resided in the lung tissue and slowly excreted from the mice, and the smaller size of ITO being cleared more slowly. Only a little ITO was transferred to other organs, especially with higher blood flow. Two type of ITO which deposit in the lung mainly impacts respiratory system and may injure liver or kidney. After sub-acute exposure to ITO, inflammation featured by neutrophils infiltration and fibrosis with both dose and size effects have been observed. Our findings revealed toxicokinetics and dose-dependent pulmonary toxicity in mice via oropharyngeal aspiration exposure, also replenish in vivo risk assessment of ITO. Collectively, these data indicate that under the current OEL, there are potential toxic effects after exposure to the ITO particles. The observed size-dependent biodistribution patterns and toxic effect might be important for approaching the hazard potential of small-sized ITO in an occupational environment.
اظهر المزيد [+] اقل [-]Exposure to 17α-ethinyl estradiol during early pregnancy affects fetal growth and survival in mice
2019
Meyer, Nicole | Santamaria, Clarisa Guillermina | Müller, Judith Elisabeth | Schumacher, Anne | Rodriguez, Horacio Adolfo | Zenclussen, Ana Claudia
17α-ethinyl estradiol (EE2) is a synthetic compound widely used in the generation of contraceptive pills. EE2 is present in the urine of women taking contraceptives and its presence has been confirmed at increasing concentrations contaminating rivers all over the world. Because of this cycle, it can entry the human food chain when watering plants. A negative influence of EE2 on fertility and reproductive capacity of wildlife was already suggested. The short-term impact of exposure to contaminating EE2 on pregnancy outcome has not been addressed.Pregnant mice were exposed to either 0.005 μg (concentrations found in water) or 5 μg EE2/kg (contraceptive dose) body weight/day from gestation day 1–7 by oral gavage. Control mice received a 0.1% ethanol solution. High frequency ultrasound imaging was used to follow-up fetal and placental growth in vivo. Doppler measurements were utilized to analyze blood flow parameters in uterine and umbilical arteries. Mice were sacrificed at gd5, 10, and 14. We show that most fetuses of mothers exposed to the high EE2 dose die intrauterine at gd10, with implantation sizes beginning to be smaller already at gd8. Mothers exposed to the low EE2 dose show an impaired remodeling of the spiral arteries, a higher placental weight and pups that are large for gestational age. The insulin-like growth factor system that regulates fetal and placental growth and development is affected by the EE2 treatment.Our results show that a short-term exposure to EE2 during early pregnancy has severe consequences for fetal growth and survival depending on the dose. Exposition to synthetic estrogens affects placenta growth and angiogenesis. These findings urge to the study of mechanisms dysregulated upon environmental exposition to estrogens.
اظهر المزيد [+] اقل [-]Ibuprofen and diclofenac impair the cardiovascular development of zebrafish (Danio rerio) at low concentrations
2020
Zhang, Kun | Yuan, Guanxiang | Werdich, Andreas A. | Zhao, Yanbin
The non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and diclofenac are highly prescribed worldwide and their presence in aquatic system may pose a potential risk to aquatic organisms. Here, we systematically assessed their cardiovascular disruptive effects in zebrafish (Danio rerio) at environmentally relevant concentrations between 0.04 and 25.0 μg/L. Ibuprofen significantly increased the cardiac outputs of zebrafish embryos at actual concentrations of 0.91, 4.3 and 21.9 μg/L. It up-regulated the blood cell velocity, total blood flow and down-regulated the blood cell density at concentrations of 4.3 μg/L and higher. In comparison, diclofenac led to inhibition of spontaneous muscle contractions and decreased hatching rate of zebrafish embryos at the highest concentration (24.1 μg/L), while it had negligible effects on the cardiac physiology and hemodynamics. Transcriptional analysis of biomarker genes involved in cardiovascular physiology, such as the significantly up-regulated nppa and nkx2.5 expressions response to ibuprofen but not to diclofenac, is consistent with these observations. In addition, both ibuprofen and diclofenac altered the morphology of intersegmental vessels at high concentrations. Our results revealed unexpected cardiovascular functional alterations of NSAIDs to fish at environmental or slightly higher than surface water concentrations and thus provided novel insights into the understanding of their potential environmental risks.
اظهر المزيد [+] اقل [-]Hemolysis associated toxicities of benthic dinoflagellates from Hong Kong waters
2020
Yan, Meng | Leung, Priscilla T.Y. | Gu, Jiarui | Lam, Veronica T.T. | Murray, J Sam | Harwood, D Tim | Wai, Tak-Cheung | Lam, Paul K.S.
Benthic dinoflagellates produce a diverse range of phycotoxins, which are responsible for intoxication events in marine fauna. This study assessed the hemolysis associated toxicities of six species of benthic dinoflagellates from the genera Coolia, Fukuyoa, Amphidinium and Prorocentrum. Results demonstrated that Amphidinium carterae, Coolia tropicalis and Fukuyoa ruetzleri were the three most toxic species, while Prorocentrum cf. lima did not have significant hemolytic effect. Grouper samples (Cephalopholis boenak) were more tolerant to the hemolytic algae than the blackhead seabream (Acanthopagrus schlegelii), with decreased heart rate and blood flow being observed in medaka larvae after exposure to toxic algal extracts. LC-MS/MS analysis detected a gambierone analogue called 44-methylgambierone produced by the C. tropicalis isolate. This analogue was also detected in the F. ruetzleri isolate. This study provided new information on the hemolysis associated toxicities of local toxic benthic dinoflagellates, which contributes to better understanding of their emerging threats to marine fauna and reef systems in Hong Kong.
اظهر المزيد [+] اقل [-]Exploring the photo protective potential of solid lipid nanoparticle-based sunscreen cream containing Aloe vera
2020
Rodrigues, Lavita Roshni | Jose, Jobin
Nowadays, the sunscreen creams are composed of mostly synthetic chemicals and other organic compounds which were found to enter into the blood stream on topical application raising concerns in the scientific community. The scientific community has now shifted their attention to herbal formulations due to toxicity of these synthetic molecules. Aloe vera is a xerophitic plant having excellent anti-oxidant properties. The permeation effect and drug stability of the drug candidate can be significantly enhanced by formulating it into solid lipid nanoparticles (SLN). The main objectives of the study were to formulate and evaluate Aloe vera-loaded SLN sunscreen cream and to determine its photoprotective potential. The Aloe vera-loaded SLNs were formulated by microemulsification technique. The developed SLNs were studied for its entrapment efficiency, poly dispersity index (PDI), zeta potential, particle size, and other characterization techniques. Finally, the optimized SLNs were incorporated into the sunscreen cream and evaluated for its spreadability, viscosity, extrudability, drug content, in vitro drug release, ex vivo permeation, determination of sun protection factor (SPF), skin irritation test, and accelerated stability studies. The in vitro SPF was found out to be 16.9 ± 2.44 and the in vivo SPF observed to be approximately 14.81 ± 3.81, respectively. Stability studies were performed under accelerated conditions and no appreciable changes in the parameters were noticed. The solid lipid nanoparticles of Aloe vera were incorporated into a cream and the SPF of the resultant sunscreen cream was found to be on par with the sunscreens that were currently available in the market.
اظهر المزيد [+] اقل [-]Effect of supra-nutritional selenium-enriched probiotics on hematobiochemical, hormonal, and Doppler hemodynamic changes in male goats
2020
Mandour, Ahmed S. | Samir, Haney | El-Beltagy, Marwa A. | Abdel-Daim, Mohamed M. | Izumi, Watanabe | Ma, Danfu | Matsuura, Katsuhiro | Tanaka, Ryou | Watanabe, Gen
In this study, the influence of supra-nutritional organic selenium (Se) supplement on hematology and plasma biochemicals, including antioxidant parameters and plasma reproductive hormones, as well as blood flow characteristics in the supratesticular and common carotid arteries (STA and CCA, respectively) were investigated. For this purpose, 15 male goats were used and classified into three equal groups according to the supplementation of the basal diet (BD): negative control (NC), probiotic (Pro), and Se-probiotic (Se-Pro) groups. Blood perfusion in the STA and CCA was assessed by Doppler ultrasonography at three different time intervals: at the experimental onset (T0), 3 weeks of dietary supplement (T3), and after 6 weeks of observation (T6). Concomitantly, blood samples were withdrawn for hematobiochemical and hormonal changes. Results revealed no evidence of clinical abnormality, with some enhanced hematological parameters and antioxidant (SOD and GPX) levels in goats of the Se-Pro and Pro groups. High concentrations of FSH were found in the Se-Pro at T6 compared to its values in other groups. Similarly, testosterone levels were elevated in the Pro and Se-Pro groups at T3 compared to other time points. There were significant increases in levels of IGF-1 in the Pro and Se-Pro groups compared to the NC group. Significant (P < 0.05) increases in the values of the blood volume within the CCA and the STA were noted in the Se-Pro group, and the highest values were observed at T6 (CCA, 427.4 ± 33 ml/min; STA, 49.9 ± 5.0 ml/min). In conclusion, supra-nutritional organic selenium improves some hematobiochemical parameters, reproductive hormones, and the blood perfusion within the CCA and STA in goats.
اظهر المزيد [+] اقل [-]Toxicity of 3,5,6-trichloro-2-pyridinol tested at multiple stages of zebrafish (Danio rerio) development
2016
Suvarchala, Gonuguntla | Philip, Gundala Harold
Organophosphate compounds (OP) are widely used throughout the world for pest control. 3,5,6-Trichloro-2-pyridinol (TCP) is a primary metabolite of two OP compounds namely CP and triclopyr. This study is carried out to know whether a metabolite of parent compound is doing well or harm to biota. The potential effect of TCP was evaluated on development as destabilization of any events transpiring during embryogenesis could be deleterious. To determine this, 4-hpf zebrafish embryos were exposed to five concentrations of TCP (200, 400, 600, 800, 1000 μg/L) or 99.5 % acetone (solvent control). Different early life-stage parameters were observed at four different developmental stages, 24, 48, 72 and 96 hpf. TCP-treated embryo/larvae showed increased mortality, delay in hatching time and decrease in percentage of hatched embryos. Reduction in heartbeat rate, blood flow and body and eye pigmentation was noticed in a dose-dependent manner. Pericardial and yolk sac edema were most severe malformations caused by TCP. Along with this crooked spine/notochord, tail deformation was noticed in hatched and unhatched embryos. The malformations observed provide a good starting point for examination of the molecular mechanisms that are affected during development by TCP. Results gain significance as TCP, which is a breakdown product, appears to be more toxic during development compared to parent compound, CP (our earlier publication).
اظهر المزيد [+] اقل [-]Dietary supplementation of Sargassum latifolium modulates thermo-respiratory response, inflammation, and oxidative stress in bacterial endotoxin-challenged male Barki sheep
2020
Ramadan, Gamal | Fouda, Wafaa A. | Ellamie, Ashgan M. | Ibrahim, Wael M.
Endotoxemia is mainly caused by translocation of bacterial lipopolysaccharides (LPS) into the bloodstream. This in turn enhances systemic inflammation and inappropriate production of reactive oxygen species, leading to oxidative injury of vital internal organs and other dangerous effects that can be life-threatening. Here, we evaluated/compared the modulatory effects of consuming two different doses (2% and 4% of the diet) of brown seaweeds (Sargassum latifolium) for 40 consecutive days on thermo-respiratory response, inflammation, and oxidative stress in Barki male sheep (Ovis aries) challenged twice with bacterial LPS (1.25 μg/kg body weight, injected intravenously on days 28 and 35 of the experimental period). The results showed that the diet containing Sargassum latifolium (especially at 4%) modulated significantly (P < 0.05–0.001) the increase in the thermo-respiratory response (skin and rectal temperatures, and respiration rate) and the obtained systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations) in the LPS-challenged sheep. In addition, it improved significantly (P < 0.001, especially at 4%) the total antioxidant capacity of the blood of LPS-challenged sheep by increasing the catalase and superoxide dismutase activities. Moreover, it decreased the blood markers of tissue damage (malondialdehyde concentration and the activities of alanine aminotransferase and lactate dehydrogenase) in the LPS-challenged sheep. In conclusion, the diet containing 4% Sargassum latifolium may have potential impact in protecting the ruminant livestock from the serious effects of endotoxemia through improving the animals’ antioxidant defense system and regulating their inflammatory and thermo-respiratory responses.
اظهر المزيد [+] اقل [-]