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Thioredoxin-albumin fusion protein prevents urban aerosol-induced lung injury via suppressing oxidative stress-related neutrophil extracellular trap formation
2021
Tanaka, Ken-ichiro | Kubota, Maho | Shimoda, Mikako | Hayase, Tomoko | Miyaguchi, Mamika | Kobayashi, Nahoko | Ikeda, Mayumi | Ishima, Yu | Kawahara, Masahiro
The number of deaths from air pollution worldwide is estimated at 8.8 million per year, more than the number of deaths from smoking. Air pollutants, such as PM₂.₅, are known to induce respiratory and cardiovascular diseases by inducing oxidative stress. Thioredoxin (Trx) is a 12-kDa endogenous protein that exerts antioxidant activity by promoting dithiol disulfide exchange reactions. We previously synthesized human serum albumin-fused thioredoxin (HSA-Trx), which has a longer half-life in plasma compared with Trx, and demonstrated its efficacy against various diseases including respiratory diseases. Here, we examined the effect of HSA-Trx on urban aerosol-induced lung injury in mice. Urban aerosols induced lung injury and inflammatory responses in ICR mice, but intravenous administration of HSA-Trx markedly inhibited these responses. We next analyzed reactive oxygen species (ROS) production in murine lungs using an in vivo imaging system. The results show that intratracheal administration of urban aerosols induced ROS production that was inhibited by intravenously administered HSA-Trx. Finally, we found that HSA-Trx inhibited the urban aerosol-induced increase in levels of neutrophilic extracellular trap (NET) indicators (i.e., double-stranded DNA, citrullinated histone H3, and neutrophil elastase) in bronchoalveolar lavage fluid (BALF). Together, these findings suggest that HSA-Trx prevents urban aerosol-induced acute lung injury by suppressing ROS production and neutrophilic inflammation. Thus, HSA-Trx may be a potential candidate drug for preventing the onset or exacerbation of lung injury caused by air pollutants.
اظهر المزيد [+] اقل [-]Critical comparison of intravenous injection of TiO2 nanoparticles with waterborne and dietary exposures concludes minimal environmentally-relevant toxicity in juvenile rainbow trout Oncorhynchus mykiss
2013
Boyle, David | Al-Bairuty, Genan A. | Henry, Theodore B. | Handy, Richard D.
A critical comparison of studies that have investigated tissue accumulation and toxicity of TiO2-NPs in fish is necessary to resolve inconsistencies. The present study used identical TiO2-NPs, toxicological endpoints, and fish (juvenile rainbow trout Oncorhynchus mykiss) as previous studies that investigated waterborne and dietary toxicity of TiO2-NPs, and conducted a critical comparison of results after intravenous caudal-vein injection of 50 μg of TiO2-NPs and bulk TiO2. Injected TiO2-NPs accumulated only in kidney (94% of measured Ti) and to a lesser extent in spleen; and injected bulk TiO2 was found only in kidney. No toxicity of TiO2 was observed in kidney, spleen, or other tissues. Critical comparison of these data with previous studies indicates that dietary and waterborne exposures to TiO2-NPs do not lead to Ti accumulation in internal tissues, and previous reports of minor toxicity are inconsistent or attributable to respiratory distress resulting from gill occlusion during waterborne exposure.
اظهر المزيد [+] اقل [-]Toxicokinetic of cyphenothrin in rabbits
2022
Özen, Ferhat | Eraslan, Gökhan
Type II pyrethroids, including cyphenothrin, have a wider efficacy and spectrum of action because they have a killing effect rather than a knockdown effect on pests. For this reason, they are among the most widely used pyrethroid groups today. In addition, this group also has repellent activity. Thus, cyphenothrin is a commonly used pyrethroid, which poses an exposure/toxicity risk for living organisms. Toxicokinetic studies have an important place in predicting the toxicity risks of compounds and evaluating viable treatment options. In this study, the toxicokinetics of cyphenothrin were investigated in rabbits. The animal material of the study comprised 6-month-old female 14 New Zealand rabbits, each weighing 2–2.5 kg. The animals were randomly assigned to two groups, each of 7 animals. The rabbits in group 1 were administered a single dose of 2.5 mg/kg bw cyphenothrin in dimethyl sulfoxide as an intravenous bolus, while the rabbits in group 2 were administered a single dose of 2.5 mg/kg bw cyphenothrin in the same vehicle as an oral bolus. Following the administration of cyphenothrin, blood samples were taken at certain intervals from the auricular vein into heparinized tubes. Plasma cyphenothrin levels were determined by gas chromatography, using a capillary column and a micro-electron capture detector. For orally administered cyphenothrin, the plasma maximum concentration (Cₘₐₓ), time to reach the maximum value (tₘₐₓ), half-life (t₁/₂ᵦ), mean residence time (MRT), area under the curve (AUC₀→∞), and bioavailability (F) values were determined as 172.28 ± 47.30 ng/ml, 1.07 ± 0.42 h, 12.95 ± 1.11 h, 17.79 ± 1.69 h, 2220.07 ± 572.02 ng/h/ml, and 29.50%, respectively. For intravenous cyphenothrin, the t₁/₂ᵦ, MRT and AUC₀→∞ values were ascertained as 7.66 ± 0.74 h, 9.28 ± 0.62 h, and 7524.31 ± 2988.44 ng/h/ml, respectively. Although the bioavailability of cyphenothrin was limited when taken orally, its half-life and mean residence time in the body were found to be long. This suggests that high doses of this pesticide may pose a poisoning risk.
اظهر المزيد [+] اقل [-]Teratological effects of titanium dioxide nanoparticles in mice embryo
2022
Ahmad, Munir | Khan, Muhammad Khalil Ahmad | Shahzad, Khurram | Ahmad, Naveed | Parveen, Munazza | Khan, Muhammad Saleem
Nanoparticles have numerous applications related to human uses. Titanium dioxide nanoparticles (TiO₂-NPs) are extensively used in many daily utilities. The small size particles and larger uses in the industry have led them to become a threatening entity to the living organisms. The unchecked use and dumping in the environment poses a significant toxicological risk to the developing mammalian embryo. The present study was conducted to determine the developmental toxicity and teratogenic effects of TiO₂-NPs in murine embryos. The TiO₂-NPs were introduced intravenously into pregnant mice graded as T1 (0.52 mg/g BW), T2 (0.7 mg/g BW), and T3 (1.05 mg/g BW) along with control with no dose administration T0 (0.00 mg/g BW). Results recorded after 14 days were resorbed fetuses, dropped wrist, hemorrhages, sacral hygromas, and kinked tails. It was concluded that the exposure of TiO₂-NPs in mentioned doses from any source may lead to deleterious effects on the development of an embryo.
اظهر المزيد [+] اقل [-]Interaction of copper with titanium dioxide nanoparticles induced hematological and biochemical effects in Clarias gariepinus
2021
Matouke, Moise Matouke | Sanusi, Hussaina Mohammed | Eneojo, Abalaka Samson
The increasing demand for engineered nanomaterials induces potential harmful impact into aquatic ecosystems and is a great concern for freshwater biodiversity. The present study showed that enhancing toxic property of titanium dioxide nanoparticles (TiO₂ NPs) with copper (Cu) was responsible for the disruption of hormonal, hematological, and biochemical activities, in Clarias gariepinus. The study revealed that C. gariepinus intravenously injected with safe concentrations of TiO₂ NPs (3μg g) and Cu (2.5 μg g) alone and binary mixtures (TiO₂ NPs (3μg g) + Cu (2.5μg g)) for a period of 96h remarkably changed hormonal activities and hematological and biochemical indices of the fish. Our findings indicated that both chemicals accumulated in vital organs (the brain, serum, heart, gonad, liver, gills, serum, and kidney) and the presence of TiO₂ NPs enhanced the bioavailability of copper. Fish exposed to TiO₂ NPs alone significantly increased thyroxine (T₄) and further decreased triidothyronine (T₃). In addition, the binary mixtures showed antagonistic effects on both hormones. The hematological indices (WBC, RBC, HGt, MCV, MCH, MCHC, and Hct) were altered in all treatment groups. Decrease in WBC, RBC, HGt, Hct, and MCV were observed. Furthermore, the co-exposure further decreased WBC (60.28%), RBC (47.10%), HGt (75.99%), Hct (25.34%), and MCV (16.18%), in contrast, MCH and MCHC increased by of 2 folds, respectively. Metabolic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) showed significant (p<0.05) increase, with additive effect in co-exposure. However, the alkaline phosphatase (ALP) activity decreased significantly in co-exposure. Significant (p<0.05) decrease of antioxidants, superoxide dismutase (SOD), glutathione transferase (GST), catalase (CAT), and metallothionein (Met) was observed in all the treatments with additive effect of 64.9%, 30.77%, and 91.31% in SOD, GST, and CAT, respectively. However, there was an increase in lipid peroxidation (MDA) in all treated fish. The results indicate that combined mixture influences the accumulation, hormonal, hematological, and biochemical factors which could affect the health of the fish.
اظهر المزيد [+] اقل [-]Synergistic effects of Ficus Carica extract and extra virgin olive oil against oxidative injury, cytokine liberation, and inflammation mediated by 5-Fluorouracil in cardiac and renal tissues of male albino rats
2021
Elghareeb, Mona M. | Elshopakey, Gehad E. | Hendam, Basma M. | Rezk, Shaymaa | Lashen, Samah
5-Fluorouracil (5-FU), a chemotherapeutic drug, has adverse effects on heart and kidney functions. Ficus Carica (fig) and extra virgin olive oil (EVOO) are natural sources which have antioxidant effects. This study investigated the synergistic effects of fig extract and EVOO against cardiac and renal damage induced by 5-FU. Forty rats were equally divided into five groups and treated with physiological saline (control), five intravenous injections of 5-FU (40 mg/kg b.w) (5-FU), fig (1 g/kg b.w/day, orally) with 5-FU (Fig/5-FU), EVOO (7 g/kg b.w/day, orally) with 5-FU (EVOO/5-FU), combined treatment of fig and EVOO with five 5-FU injections (Fig/EVOO/5-FU). After 30 days, blood and tissue samples (Heart and kidney) were collected to be used in the examinations. 5-FU significantly increased serum creatine kinase activity, renal biomarkers, cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-α, and interleukin-1β as well as cardiac and renal lipid peroxides (malondialdehyde). Meanwhile, serum levels of immunoglobulins, interleukins (IL-10, IL-12), and antioxidants of heart and kidney tissues were significantly decreased in 5-FU group. It also downregulated cardiac and renal Bcl2, and upregulated cardiac troponin and renin gene expressions. As well, histological alterations clarified that 5-FU induced cardiac cell damage, distorted renal corpuscles and tubules, inflammatory cell infiltrations, and severe congestion and hemorrhage in the blood vessels. The treatment with fig and olive oil, especially the combined treatment, modulated the toxic effect of 5-FU on the heart and kidney. Our results revealed that fig extract and EVOO have a powerful antioxidant and many protective effects against cardiac and renal toxicity induced by 5-FU, especially when using fig and EVOO together as a combined treatment.
اظهر المزيد [+] اقل [-]Chlordecone disappearance in tissues of growing goats after a one month decontamination period—effect of body fatness on chlordecone retention
2016
Lastel, Marie-Laure | Lerch, Sylvain | Fournier, Agnès | Jurjanz, Stefan | Mahieu, Maurice | Archimède, Harry | Feidt, Cyril | Rychen, Guido
Chlordecone (CLD) is an organochlorine pesticide whose extended use led to the contamination of at least 20 % of agricultural soils from the French West Indies. Livestock reared on polluted areas are involuntary contaminated by CLD and their level of contamination may exceed the threshold values set by the European Union. Thus, characterizing the CLD behaviour in farm animals appear as a real issue in terms of food safety for local populations. The aim of this experiment was (i) to characterize the CLD disappearance in various tissues after exposure cessation and (ii) to evaluate the potential effect of body fatness on this process. Two groups of eight growing goats were submitted to either a basal diet or a high energy diet for 50 days before being intravenously contaminated with 1 mg CLD kg⁻¹ body weight. Two days after CLD contamination, half of the kids of each experimental group were slaughtered in order to determine pollutant levels in the serum, liver, adipose tissues, and empty carcass. The remaining animals were submitted to a 30-day decontamination period before slaughtering and measurements as described above. The implemented nutritional plan resulted in both groups of kids with significant differences in terms of body fatness. CLD was mainly concentrated in the liver of animals as described in the literature. It was found also in kids’ empty carcass and adipose tissues; however its levels in the empty carcass (muscles and bones) were unexpected since they were higher than in fat. These results indicate that the lipophilic pollutant CLD is found mainly in liver but also in muscles and fat. Concerning the animals’ depuration, a 30-d decontamination period was sufficient to observe a decrease of CLD levels by more than 75 % in both experimental groups and neither CLD concentrations nor CLD amounts were significantly affected by kids’ body fatness.
اظهر المزيد [+] اقل [-]Linear toxicokinetic of chlordecone in ewe’s serum
2020
Saint-Hilaire, Maïlie | Rychen, Guido | Thomé, Jean-Pierre | Joaquim-Justo, Célia | Le Roux, Yves | Feidt, Cyril | Fournier, Agnès
Chlordecone (CLD) is an organochlorine pesticide used in banana fields of the French West Indies between 1972 and 1993. This use resulted in a long-term pollution of soils and the possible contamination of farm animals. Indeed, after involuntary ingestion of soil, CLD is absorbed and consequently leads to contaminated animals. The aim of this study was the determination of CLD half-life and the establishment of the linearity of CLD disappearance kinetics in non-lactating adult’s ewes. Chlordecone diluted in cremophor was intravenously administrated to ewes at different doses: 0.04, 0.2, or 1 mg kg⁻¹ body weight (n = 5 for each dose). Blood samples were collected from time t = 0 to time t = 84 days. Serum samples were extracted with a solid-phase extraction and analyzed by electron capture detection gas chromatography. A two-compartmental model was applied to the serum CLD kinetics. An additional statistical analysis was applied to the observed elimination parameters in serum according to the administrated dose, and no significant differences were detected. The linear elimination of CLD between 0.04 and 1 mg kg⁻¹ body weight allowed the possibility of ewe’s extrapolation half-life in this dose range. The estimated mean CLD half-life in ewes was 24 days. Overall, the results of this study will be useful to establish decontamination strategies in small ruminants reared in contaminated CLD areas. Graphical abstract Experimental design of the CLD toxicokinetic study in ewes
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 [-]Mesenchymal stem cells ameliorate oxidative stress, inflammation, and hepatic fibrosis via Nrf2/HO-1 signaling pathway in rats
2021
Khadrawy, Sally M. | Mohamed, Hanaa M. | Mahmoud, Ayman M.
Liver fibrosis occurs in most types of chronic liver diseases and can develop into cirrhosis and liver failure. Bone marrow-derived mesenchymal stem cells (BMSCs) showed promising effects in the treatment of fibrosis. This study evaluated the possible role of Nrf2/HO-1 signaling in the ameliorative effect of BMSCs against carbon tetrachloride (CCl₄)-induced liver fibrosis, oxidative stress, and inflammation in rats. Hepatic fibrosis was induced by subcutaneous injection of CCl₄ twice per week for 6 consecutive weeks and rat BMSCs were administered intravenously. After 4 weeks, the rats were sacrificed, and samples were collected for analysis. CCl₄-intoxicated rats showed elevated serum transaminases, ALP, γGT, bilirubin and pro-inflammatory cytokines, and decreased albumin. Hepatic NF-κB p65 and malondialdehyde (MDA) were significantly increased, and cellular antioxidants were decreased in CCl₄-intoxicated rats. BMSCs ameliorated liver function markers, suppressed MDA, NF-κB p65, and inflammatory cytokines, and enhanced antioxidants in the liver of CCl₄-intoxicated rats. BMSCs were engrafted within the liver tissue and prevented histological alterations and collagen accumulation induced by CCl₄. In addition, BMSCs upregulated hepatic Nrf2 and HO-1 expression in CCl₄-intoxicated rats. In conclusion, this study provides evidence that BMSCs suppress oxidative stress, inflammation, and liver fibrosis through a mechanism involving activation of the Nrf2/HO-1 signaling.
اظهر المزيد [+] اقل [-]