scholarly journals Developmental Toxicity and Neurotoxicity Assessment of R-, S-, and RS-Propylene Glycol Enantiomers in Zebrafish (Danio Rerio) Larvae

Author(s):  
Chao Shen ◽  
Xijing Zhao ◽  
Chengyong He ◽  
Zhenghong Zuo

Abstract Propylene glycol (PG) is widely used in the foods, pharmaceuticals, oil industry, animal feed, cosmetics and other industries. Because of the existence of a chiral carbon center, PG forms R (Rectus)- and S (Sinister)-enantiomers. Currently, the toxicity study of its R-, S-enantiomers is still very scarce. In this study, we have assessed the developmental toxicity and neurotoxicity of the R-, S-, and RS-PG enantiomers in zebrafish larvae. We found that exposure to R-, S-, and RS-PG enantiomers did not significantly affect the basic developmental endpoints of embryos or larvae (i.e., embryonic movement, hatching, mortality, malformation, heartbeat, body length), indicating that R-, S-, and RS-PG exposures did not exhibit the basic developmental toxicity in zebrafish larvae. The toxicity of the three enantiomers was lower than that of ethanol, and there was no significant difference between them. However, R-, S-, and RS-PG exposures with high doses could significantly change the eye diameter and the locomotor activity of larval zebrafish, indicating that R-, S-, and RS-PG enantiomers of high doses can potentially exhibit the neurotoxicity and ocular developmental toxicity in zebrafish larvae. Therefore, the potential neurotoxicity and ocular developmental toxicity of R-, S-, and RS-PG enantiomers for infants and toddlers should be considered.

2020 ◽  
Vol 31 (3) ◽  
pp. 91-107 ◽  
Author(s):  
Najihah Azman ◽  
Nur Ain Izzati Mohd Zainudin ◽  
Wan Norhamidah Wan Ibrahim

Fumonisin B1 (FB1) is a common mycotoxin produced by Fusarium species particularly F. proliferatum and F. verticillioides. The toxin produced can cause adverse effects on humans and animals. The objectives of this study were to detect the production of FB1 based on the amplification of FUM1 gene, to quantify FB1 produced by the isolates using Ultra-fast Liquid Chromatography (UFLC) analysis, to examine the embryotoxicity effect of FB1 and to determine EC50 toward the larvae of zebrafish (Danio rerio). Fifty isolates of Fusarium species were isolated from different hosts throughout Malaysia. Successful amplification of the FUM1 gene showed the presence of this gene (800 bp) in the genome of 48 out of 50 isolates. The highest level of FB1 produced by F. proliferatum isolate B2433 was 6677.32 ppm meanwhile F. verticillioides isolate J1363 was 954.01 ppm. From the assessment of embryotoxicity test of FB1 on larvae of zebrafish, five concentrations of FB1 (0.43 ppm, 0.58 ppm, 0.72 ppm, 0.87 ppm and 1.00 ppm) were tested. Morphological changes of the FB1 exposed-larvae were observed at 24 to 168 hpf. The mortality rate and abnormality of zebrafish larvae were significantly increased at 144 hpf exposure. Meanwhile, the spontaneous tail coiling showed a significant difference. There were no significant differences in the heartbeat rate. As a conclusion, the presence of FUM1 in every isolate can be detected by FUM1 gene analysis and both of the species produced different concentrations of FB1. This is the first report of FB1 produced by Fusarium species gave a significant effect on zebrafish development.


2021 ◽  
Vol 322 ◽  
pp. 02016
Author(s):  
Uthpala Padeniya ◽  
Shafira Septriani ◽  
Arjay Pataueg ◽  
Christopher L. Brown

Microbial diversity within an aquatic community can be used to increase the growth and development of organisms. In this study, Zebrafish larvae were reared in three treatments 1) a probiotic containing 17 strains of Lactobacillus spp., 2) an amoxicillin solution, 3) water from the broodstock culture tank as the control. Survival of the larvae throughout 10 dpf was recorded. To determine the development of the gastrointestinal tract DASPEI stain was used for larvae at the age of 3 dpf to 6dpf. The intensity of the fluorescence in each larva was observed through the automated digital microscope. According to the experiment results, a significant difference (P<0.0001) in the survival rates among all treatments was recorded. The probiotic-treated larvae (PTL) had a higher survival rate. This could be due to the presence of lactic acid bacteria in the probiotic treatment, which helps in enhancing immunity. In DASPEI staining, also PTL exhibits more fluorescence in the GI tract at 24 hours to 48 hours post-hatch than the other two treatments. The main possible reason behind this could also be the presence of Lactobacillus spp. Which directly influences the higher activity of the digestive system.


1994 ◽  
Vol 72 (05) ◽  
pp. 672-675 ◽  
Author(s):  
Nicolas W Shammas ◽  
Michael J Cunningham ◽  
Richard M Pomearntz ◽  
Charles W Francis

SummaryTo characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrino-peptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation ((3-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.


1956 ◽  
Vol 102 (428) ◽  
pp. 576-588 ◽  
Author(s):  
Edward Marley

Sakel (1938a) drew attention to the difficulty of establishing satisfactory comas in a minority of patients attending for Deep Insulin therapy. This phenomenon has since been confirmed by other workers including Tillim (1938) whose patient received 500 units of insulin without the production of deep coma, by Hall (1940) who reported an instance in which 1,000 units of insulin was equally unsuccessful, by Reznikoff and Scott (1942) who described how neither 120 nor 1,000 units of insulin when injected intravenously produced any significant difference in hypoglycaemia in insulin resistant patients, and more recently by Fogarty (1953) whose case required 5,000 units of insulin for the production even of sopor. Other recorded examples of resistance to massive doses of insulin include those of Bantinget al.(1938) and Tennent (1944).Various explanations of this perverse response to insulin have been formulated, including that of Jones (1939) who proposed that resistance to insulin was both a problem of true insulin insensitivity and also of an anomalous response of the central nervous system to hypoglycaemia. Medunaet al.(1942) preferred to ascribe it to anti-insulin factors in the blood, but a more interesting interpretation derived from Freudenberg (1952) who suggested that if the effects of high insulin dosage employed in insulin coma treatment were regarded as a special instance of a stress response, then the fluctuations and differences in response could be equated in terms of the General Adaptation Syndrome of Selye. High doses were thus an index of an effective “alarm stage” characterized by a discharge from plentiful adrenocortical reserves.


1986 ◽  
Vol 5 (4) ◽  
pp. 189-196 ◽  
Author(s):  
R. F. Mankes ◽  
V. Renak ◽  
J. Fieseher ◽  
R. Lefevre

The embryotoxic effects of high doses of the narcotizing ethanol dimer 1,3-butanediol were evaluated in pregnant Long-Evans rats during the “critical period” of organogenesis. Butanediol was given by gavage at levels of 0,7060,4236, or 706 mg/kg per day (24,14.4, or 2.4% of the acute oral LD50 value for rats). Maternal sedation was observed at 7060 and 4236 mg/kg, but feed consumptions and maternal body weights were unaffected. Butanediol caused a significant, dose-dependent decrease in offspring birthweights. At the highest butanediol dose, birthweights were preferentially and significantly decreased in male pups not contiguous in utero to female siblings. Other group I1 offspring were not affected and did not differ significantly from controls. As butanediol was given prior to the period of greatest fetal growth and fetal sex steroidogenests, it is concluded that intra-uterine levels of female sex steroids (estradiol) enhance fetal repair of cellular damage (restitution ad integrum), whereas testosterone inhibits fetal repair or exacerbates previous embryonic damage by some unknown mechanism. Such interaction furthers the concept that intrauterine position affects the endpoints of developmental toxicity, as expressed at partuition.


Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 395
Author(s):  
Hélio Costa ◽  
Eloisa Saliba ◽  
Marco Bomfim ◽  
Ângela Maria Lana ◽  
Ana Luiza Borges ◽  
...  

The aim of this study was to evaluate the effects of Zinc sulfate and propylene glycol (PG) on methane (CH4) emission, nutrient intake, digestibility, and production in sheep grazing on a native Caatinga (Brazilian semi-arid savannah) pasture during the rainy season (from March to June 2014). Fifteen mixed Santa Inês sheep, all non-castrated males, with initial body weight of 19.8 ± 1.64 kg, and 4 ± 0.35 months of age, were distributed in a complete randomized design into three treatments: control (CT)—concentrate supplemented at 0.7% of body weight; CT + 300 mg of Zn/day; and CT + 2.5 mL of propylene glycol/kg LW0.75/day. Measurements were done in four periods during the rainy season, with 28 days of interval between each measurement. CH4 emission was measured using the SF6 tracer gas technique. CH4 emission per day was greater in PG than in CT and Zn (p < 0.05). However, no additive effect was observed on the intakes of organic matter (OM) and neutral detergent fiber (NDF), or on CH4 emission expressed as a function of OM and NDF intakes (p > 0.05). Across the months of the trial, OM and NDF intakes were greater in March, while the greatest emission of CH4 (g/day and g by g/OM intake) was observed in May (p < 0.05). Total CH4 emission (kg) from March to June (112 days of evaluation) was greater in PG compared with CT and Zn (p < 0.05). Zinc and PG had no effect on total CH4 emission when it was expressed per unit of body weight gain or carcass production (p > 0.05). The results of this study indicate that Zinc sulfate and propylene glycol have no beneficial effects in mitigating sheep CH4 emission. The CH4 emissions originated from sheep grazing native Caatinga pasture change throughout the rainy season due to fluctuations in availability and quality of pasture biomass. Moreover, the inclusion of zinc sulfate or propylene glycol did not improve animal feed intake, nutrient digestibility, and animal performance.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Nader Salari ◽  
Mohsen Kazeminia ◽  
Aliakbar Vaisi-Raygani ◽  
Rostam Jalali ◽  
Masoud Mohammadi

Background. Aflatoxins are found in various types of food and animal feed. Food contamination with aflatoxin toxin is of particular importance today. Various studies have reported different prevalence of aflatoxin M1 in animal milk. Therefore, due to the importance of this toxin, its role in health, and lack of general statistics about it worldwide, the present study aimed to determine the prevalence of aflatoxin M1 in milk worldwide with a systematic review and meta-analysis study. Methods. In this review study, national and international databases were extracted from SID, MagIran, IranMedex, IranDoc, Embase, ScienceDirect, Scopus, PubMed, and Web of Science (ISI) between January 1988 and February 2020. A random effects model was used for analysis, and heterogeneity of studies with an I2 index was investigated. Data were analyzed using Comprehensive Meta-Analysis (version 2). Results. The prevalence of aflatoxin M1 in milk worldwide from January 1988 to February 2020 in 122 articles with a sample size of 18921 was 79.1% (95% CI: 75.5–82.3%). Regarding the heterogeneity based on metaregression, there was a significant difference between the effect of the year of study (p≤0.001) and sample size (p≤0.001) with the prevalence of aflatoxin M1 in animal milk. Conclusion. The results of this study show that the prevalence of aflatoxin M1 in milk is high worldwide. Therefore, considering the importance of the milk group and its products, special measures should be taken to protect the ration from aflatoxin molds and milk quality.


2016 ◽  
Vol 55 (06) ◽  
pp. 228-235 ◽  
Author(s):  
Limin Tang ◽  
Tiekun Ma ◽  
Fengyu Wu

SummaryThe aim of the study was to investigate the effects of rhTSH stimulation before 131I treatment in patients with MNG. Methods: Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS database (all until January 2016). Randomized controlled trials (RCTs) that assessed the efficacy of rhTSH-stimulated 131I treatment compared to placebo or 131I treatment alone were collected. Two authors performed the data extraction independently. Results: Six RCTs involving 294 patients with MNG were included in this review. Altogether 168 patients were randomized to rhTSH-stimulated 131I therapy, and 126 to either placebo and 131I or 131I alone. rhTSH-stimulated 131I vs placebo and 131I or 131I alone for MNG showed no statistically significant difference in quality of life and all-cause mortality. rhTSH- (at a dose of 0.03 mg and above) stimulated 131I treatment for MNG showed significant benefits in thyroid volume reduction. 131I treatment with rhTSH stimulation at high doses (0.03 mg, 0.1 mg, 0.3 mg and 0.45 mg) for MNG caused significantly higher adverse effects and hypothyroidism. Conclusions: The overall results indicated that using rhTSH at high doses of 0.03–0.45 mg before 131I therapy resulted in a greater TVR than 131I therapy alone for patients with non-toxic MNG. However, an increased incidence of adverse effects and hypothyroidism was observed in patients receiving highdose of rhTSH pretreatment than in patients who received low-dose rhTSH pretreatment. Therefore, a dose of 0.03 mg rhTSH pretreatment before 131I therapy may be more potent than 131I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.


2005 ◽  
Vol 51 (11) ◽  
pp. 2085-2094 ◽  
Author(s):  
Sherri L Kacinko ◽  
Allan J Barnes ◽  
Eugene W Schwilke ◽  
Edward J Cone ◽  
Eric T Moolchan ◽  
...  

Abstract Background: Sweat testing is a noninvasive technique for monitoring drug exposure in treatment, criminal justice, and employment settings. Methods: We evaluated cocaine excretion in 9 participants’ sweat after they received 3 low doses (75 mg/70 kg) of cocaine HCl subcutaneously within 1 week and, 3 weeks later, 3 high doses (150 mg/70 kg). Six additional participants completed portions of the study. PharmChek® sweat patches (n = 1390) were collected throughout a 3-week washout period, reflecting previously self-administered drugs, and during and after controlled dosing. Results: Cocaine was the primary analyte detected with 24% of patches positive at the gas chromatography–mass spectrometry limit of quantification of 2.5 ng/patch and 7% of patches at the proposed Substance Abuse and Mental Health Services Administration cutoff of 25 ng/patch. Ecgonine methyl ester (EME) was detected more often and at generally higher concentrations than benzoylecgonine. In patches containing both metabolites, there was no statistically significant difference in the benzoylecgonine/EME ratio based on length of patch wear. During washout, 2 participants’ weekly patches tested positive (≥25 ng/patch) during the first week; one remained positive during week 2; and none were positive during week 3. Cocaine and EME were detectable within 2 h; benzoylecgonine was not detected until 4–8 h after low doses and slightly sooner after high doses. The majority of drug was excreted within 24 h. Over 70% of weekly patches worn during low doses were positive for cocaine (≥25 ng/patch), increasing to 100% during high doses. Conclusion: Sweat testing is an effective and reliable method of monitoring cocaine exposure.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3414-3414
Author(s):  
Dorothee Leroux ◽  
Claire Pouplard ◽  
Benoit Guillet ◽  
Beatrice Cosne ◽  
Marc Antoine May ◽  
...  

Abstract Backgroud and objectives: The formation of antibodies (Abs) to heparin platelet factor 4 complexes (H/PF4) associated with heparin-induced thrombocytopenia (HIT) is a T-helper cell dependent event that involves antigen presenting cells (APC) and B-lymphocytes. Polymorphisms of the CTLA-4 (cytotoxic T lymphocyte antigen 4) gene have been described as a risk factor in several autoimmune diseases. In addition, TNFα is a major inflammatory cytokine with potent regulatory functions and polymorphisms in TNFA have also been associated with autoimmune antibody-mediated diseases. We therefore evaluated the possibility that an association between polymorphisms in CTLA-4 (−318 C/T and +49 A/G) or TNFA (−308 G/A) and the development of Abs to H/PF4 and HIT might exist. Methods: Eighty-three patients identified as having developed definite HIT with significant levels of Abs to PVS/PF4 in ELISA (HAT 45, GTI, Brookfield, WI, USA) and positive serotonin release assay were studied (HIT group). Two control groups were studied: the Abneg group consisted of 83 patients who had undergone heart surgery with high doses of unfractionated heparin administered during cardiopulmonary bypass (CPB), and who were tested negative for Abs to PVS/PF4 at the 8th post operative day. The Abpos group consisted of 58 patients who had also undergone CPB but had developed high levels of Abs to PVS/PF4 without significant change in the platelet count post-operatively. Three single nucleotide polymorphisms (SNPs), one in TNFA (−308G/A) and two in CTLA-4 (−318 C/T and +49A/G) were studied by conventional RFLP analysis as described (Astermark et al, Blood 2006 and Astermark et al, Thromb Haemost 2007). Results: The CTLA-4 +49 A/G and −318 C/T genotypes and allele distributions were similar in the 3 groups of patients (Table). In contrast, the frequency of TNFA –308 G/G homozygotes was higher in the HIT group compared to patients without HIT whether they had developed PF4-specific Abs or not (p=0.035). Therefore, the A allele was less frequent in HIT patients (p=0.026, OR 0.49; CI95% 0.26–0.93) but there was no significant difference when comparing patients with and without PF4-dependent antibodies. Genotype Allele frequency Ab neg (n = 82) Ab pos (n = 58) HIT (n = 82) CTLA-4(+49) A/A 31 (38%) 24 (41%) 35 (43%) A/G 40 (49%) 26 (45%) 41 (50%) G/G 11 (13%) 8 (14%) 6 (7%) CTLA-4(−318) C/C 63 (77%) 49 (84%) 67 (82%) C/T 19 (23%) 9 (16%) 17 (21%) T/T 0 0 0 (0%) TNFα(−308) G/G 59 (72%) 41 (71%) 68 (84%) G/A 20 (24%) 15 (26%) 12 (15%) A/A 3 (4%) 2 (3%) 1 (1%) A Allele 0.160 0.160 0.09 G Allele 0.840 0.840 0.910 Conclusion: The TNFA –308 A allele appears to be protective regarding the risk of heparin-induced thrombocytopenia in patients having developed PF4-specific antibodies. A similar effect has been suggested in immune thrombocytopenic purpura (Foster et al, Brit J Haematol 2001) despite individuals with this allele have been identified as high TNFα producers. Therefore, the mechanisms involved for explaining this apparent protective effect of the TNFA −308A allele in patients at risk for HIT have to be identified.


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