scholarly journals Investigating the Cardiac Effects of Sildenafil loaded Nanoparticles on Heart Failure using the Zebrafish Embryo Model

2020 ◽  
Author(s):  
Heba Adel Mohamed Lotfy Moussa ◽  
Gawaher Saleh Abbas Mahgoub ◽  
Mashael Ali H I Al-Badr ◽  
Huseyin Cagatay Yalcin
Keyword(s):  
Heart Failure ◽  
Zebrafish Embryo ◽  
Drug Effects ◽  
Toxicity Assessment ◽  
Negative Control ◽  
Hatching Rate ◽  
Systematic Effect ◽  
Conventional Drug ◽  
Cardiovascular Therapy ◽  
Heart Injury

Background: Cardiovascular diseases (CVDs) are the first cause of death worldwide. Vasolidator agents are used to relax cardiac muscle, but their extremely short half-lifes limit their effectiveness. Sildenafil is such an agent used to relax the blood vessels muscles and increase the blood flow. The conventional drug can lead to serious problems in patients duo to the systematic drug delivery. Use of Nanomedicine potentially can enhance delivery of this agent while reducing the systematic effect of the drug. Aim: The purpose of the research is to examine the effectiveness sildenafil loaded nanoparticles in rescuing heart failure using zebrafish embryo model. Methods: There will be five experimental groups. The zebrafish will be treated with Aristolochic Acid (AA) at 24 hour per fertilization (hpf) to create the heart injury group. The treatment groups will be heart injury followed by a dose of either Sildenafil or Sildenafil loaded nanoparticles at 36 hpf. Two control groups will be the negative control (exposed to egg water) and vehicle control (exposed to the Dimethylsulfoxide (DMSO)).To evaluate the drug effects on embryo, toxicity assessment (Survival rate, tail flicking and hatching rate), cardiotoxicity assessment and gene expression of heart injury marker via RT-PCR will be conducted. Results: Preliminary findings demonstrate, loading Sildenafil to nanoparticles enhances its effectiveness dramatically. The experiments are ongoing to confirm the results. Conclusion: Nanomedicine is a powerful approach to enhance cardiovascular therapy. Vasodilator drugs in particular will benefit from this improvement as demonstrated with our findings

scholarly journals Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

2020 ◽  
Vol 93 ◽  
pp. 219-229 ◽  
Author(s):  
Ségolène Siméon ◽  
Katharina Brotzmann ◽  
Ciaran Fisher ◽  
Iain Gardner ◽  
Steve Silvester ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Zebrafish Embryo ◽  
Pbpk Model ◽  
Developmental Toxicity ◽  
Toxicity Assessment

scholarly journals Comparison of the Efficacy of Hydrogen Peroxide and Salt for Control of Fungal Infections on Brown Trout (Salmo trutta) Eggs

2018 ◽  
Vol 46 (1) ◽  
pp. 5 ◽  
Author(s):  
Nikolina Novakov ◽  
Vladislav Mandić ◽  
Brankica Kartalović ◽  
Bojana Vidović ◽  
Nenad Stojanac ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Sodium Chloride ◽  
Malachite Green ◽  
Brown Trout ◽  
Active Ingredient ◽  
Fungal Infections ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Hatching Rate

Background: Fungal infections can cause serious problems infecting fish eggs, especially unfertilized or dead eggs. In the past, this problem was solved by using very effective chemicals such as malachite green and formalin. But, due to its toxicity and carcinogenicity, malachite green was banned for use in fish intended for human consumption. Formalin also has been banned in most countries. Chemicals and drugs recommended for use to treat fungal infections are hydrogen peroxide, salt, potassium permanganate etc. The goal of the present study was to determine and compare the efficacy of antifungal effects of hydrogen peroxide and sodium chloride on brown trout eggs.Materials, Methods & Results: The experiment was conducted in the brown trout hatchery, Šipovo, Bosnia and Herzegovina. The experimental groups contained 500 and 1000 mg/L of hydrogen peroxide with 15 and 30 min of exposition; 1 and 2.5% of sodium chloride with 15 and 30 min of exposition and a negative control group (no chemical treatment). The treatment concentrations were calculated and prepared from hydrogen peroxide of 35% active ingredient, and sodium chloride (sterilized) of 100% active ingredient. Eggs for the study were spawned from 11 females and 4 males. The first treatment was performed on the fourth day, and each next treatment was performed at 3-day intervals. Six treatments were administered until the 19th day after the fertilization. The treatment of the eggs was provided until the eggs reached the eyed stage. The effectiveness of the chemical treatments was measured by a hatch rate. There was a significant difference between all treated groups and the negative control group (P < 0.05). Hydrogen peroxide with a concentration of 500 mg/L for 30 min was the most effective and demonstrated a higher hatching rate (75.7%). Sodium chloride treatments resulted in statistically significantly lower hatching rates than hydrogen peroxide treatments. The hatching rate in salt treatment with a concentration of 2.5% for 30 min was 27.3% lower than in hydrogen peroxide treatment with a concentration of 500 mg/L for 30 min.Discussion: Hydrogen peroxide is an effective antifungal, antibacterial and antiviral compound, and according to the Food and Drug Administration (FDA), hydrogen peroxide and salt are approved and classified as a low regulatory priority for the control of oomycetes on all species and life stages of fish. It is considered to be a very environmentally compatible chemical because it does not produce any toxic bioproducts when it decomposes. Hydrogen peroxide stood out as the best candidate substance for fungal control. The fact that the treatment with hydrogen peroxide at a concentration of 500 mg/L for 30 min was more effective than treatments at a concentration of 1000 mg/L can be explained by temperature dependency and treatment frequency of this chemical. Salt was not such an effective fungicide as hydrogen peroxide. When using salt, toxicity to the eggs should also be considered. Salt solutions may cause egg deaths at levels of 2.5% or higher. It is possible that high salinities have an inhibitory effect on the movement of fish embryo due to the high osmotic impact on the perivitelline layer. Thus, hydrogen peroxide has proven to be efficient, inexpensive, easy to use and environmentally safe in preventing fungal infections on brown trout eggs.

HFrEF pharmacological treatment: ACEIs and/or ARBs

ESC CardioMed ◽  
2018 ◽  
pp. 1844-1848
Author(s):  
Marc A. Pfeffer
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Drug Effects ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction

Several classes of inhibitors of the renin–angiotensin system were developed as antihypertensive agents. Following the early observations of favourable haemodynamic effects of angiotensin-converting enzyme inhibitors (ACEIs) in patients with congestive heart failure, a series of major randomized outcome trials demonstrated morbidity and mortality benefits of these agents across the spectrum of patients with heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor blockers (ARBs) were then also shown to have similar benefits with a suggestion of some incremental improvements when used together. However, in the trials that randomized patients to a proven dose of an ACEI plus either placebo or an ARB, the combination of the two inhibitors of the renin–angiotensin system resulted in more adverse drug effects without a meaningful improvement in clinical outcomes. This chapter reviews the fundamental underpinnings for use of either an ACEI or ARB to improve prognosis of patients with HFrEF.

scholarly journals Ecotoxicological Assessment of Thermally- and Hydrogen-Reduced Graphene Oxide/TiO2 Photocatalytic Nanocomposites Using the Zebrafish Embryo Model

Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 488 ◽  
Author(s):  
Halema Al-Kandari ◽  
Nadin Younes ◽  
Ola Al-Jamal ◽  
Zain Z. Zakaria ◽  
Huda Najjar ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Zebrafish Embryo ◽  
Rating Scale ◽  
Hatching Rate ◽  
Ecotoxicological Assessment ◽  
Tio2 Photocatalysts ◽  
Reduced Graphene ◽  
Hematopoietic Toxicity ◽  
Water Pollution Management

Advanced oxidation processes (AOPs) have recently attracted great interest in water pollution management. Using the zebrafish embryo model, we investigated the environmental impacts of two thermally (RGOTi)- and hydrogen (H2RGOTi)-reduced graphene oxide/TiO2 semiconductor photocatalysts recently employed in AOPs. For this purpose, acutoxicity, cardiotoxicity, neurobehavioral toxicity, hematopoietic toxicity, and hatching rate were determinate. For the RGOTi, the no observed effect concentration (NOEC, mortality/teratogenicity score <20%) and the median lethal concentration (LC50) were <400 and 748.6 mg/L, respectively. H2RGOTi showed a NOEC similar to RGOTi. However, no significant mortality was detected at all concentrations used in the acutoxicity assay (up to1000 mg/L), thus indicating a hypothetical LC50 higher than 1000 mg/L. According to the Fish and Wildlife Service Acute Toxicity Rating Scale, RGOTi can be classified as “practically not toxic” and H2RGOTi as “relatively harmless”. However, both nanocomposites should be used with caution at concentration higher than the NOEC (400 mg/L), in particular RGOTi, which significantly (i) caused pericardial and yolk sac edema; (ii) decreased the hatching rate, locomotion, and hematopoietic activities; and (iii) affected the heart rate. Indeed, the aforementioned teratogenic phenotypes were less devastating in H2RGOTi-treated embryos, suggesting that the hydrogen-reduced graphene oxide/TiO2 photocatalysts may be more ecofriendly than the thermally-reduced ones.

Adrenomedullin-epinephrine cotreatment enhances cardiac output and left ventricular function by energetically neutral mechanisms

2012 ◽  
Vol 302 (8) ◽  
pp. H1584-H1590
Author(s):  
Thor Allan Stenberg ◽  
Anders Benjamin Kildal ◽  
Ole-Jakob How ◽  
Truls Myrmel
Keyword(s):  
Heart Failure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Acute Heart Failure ◽  
Coronary Blood Flow ◽  
Drug Effects ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Energetic Cost ◽  
Lv Function

Adrenomedullin (AM) used therapeutically reduces mortality in the acute phase of experimental myocardial infarction. However, AM is potentially deleterious in acute heart failure as it is vasodilative and inotropically neutral. AM and epinephrine (EPI) are cosecreted from chromaffin cells, indicating a physiological interaction. We assessed the hemodynamic and energetic profile of AM-EPI cotreatment, exploring whether drug interaction improves cardiac function. Left ventricular (LV) mechanoenergetics were evaluated in 14 open-chest pigs using pressure-volume analysis and the pressure-volume area-myocardial O2 consumption (PVA-MV˙o2) framework. AM (15 ng·kg−1·min−1, n = 8) or saline (controls, n = 6) was infused for 120 min. Subsequently, a concurrent infusion of EPI (50 ng·kg−1·min−1) was added in both groups (AM-EPI vs. EPI). AM increased cardiac output (CO) and coronary blood flow by 20 ± 10% and 39 ± 14% (means ± SD, P < 0.05 vs. baseline), whereas controls were unaffected. AM-EPI increased CO and coronary blood flow by 55 ± 17% and 75 ± 16% ( P < 0.05, AM-EPI interaction) compared with 13 ± 12% ( P < 0.05 vs. baseline) and 18 ± 31% ( P = not significant) with EPI. LV systolic capacitance decreased by −37 ± 22% and peak positive derivative of LV pressure (dP/d tmax) increased by 32 ± 7% with AM-EPI ( P < 0.05, AM-EPI interaction), whereas no significant effects were observed with EPI. Mean arterial pressure was maintained by AM-EPI and tended to decrease with EPI (+2 ± 13% vs. −11 ± 10%, P = not significant). PVA-MV˙o2 relationships were unaffected by all treatments. In conclusion, AM-EPI cotreatment has an inodilator profile with CO and LV function augmented beyond individual drug effects and is not associated with relative increases in energetic cost. This can possibly take the inodilator treatment strategy beyond hemodynamic goals and exploit the cardioprotective effects of AM in acute heart failure.

scholarly journals Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018

2021 ◽  
Author(s):  
Susan X. Zhao ◽  
Andres Deluna ◽  
Kate Kelsey ◽  
Clifford Wang ◽  
Aravind Swaminathan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Health Planning ◽  
Statistical Significance ◽  
Negative Control Group ◽  
International Classification Of Diseases ◽  
Negative Control ◽  
Control Group ◽  
Public Health Response ◽  
Classification Of Diseases ◽  
Age Adjusted Rates

BACKGROUND: Methamphetamine-associated cardiomyopathy/heart failure (MethHF) is an increasingly recognized disease entity in the context of a rising methamphetamine (meth) epidemic that most severely impacts the western United States. Using heart failure (HF) hospitalization data from the Office of Statewide Health Planning and Development, this study aimed to assess trend and disease burden of MethHF in California. METHODS: Adult patients (≥18 years old) with HF as primary hospitalization diagnosis between 2008 and 2018 were included in this study. The association with Meth (MethHF) and those without (non-MethHF) were determined by meth-related International Classification of Diseases -based secondary diagnoses. Statistical significance of trends in age-adjusted rates of hospitalization per 100 000 adults were evaluated using nonparametric analysis. RESULTS: Between 2008 and 2018, 1 033 076 HF hospitalizations were identified: 42 565 were MethHF (4.12%) and 990 511 (95.88%) were non-MethHF. Age-adjusted MethHF hospitalizations per 100 000 increased by 585% from 4.1 in 2008 to 28.1 in 2018, while non-MethHF hospitalizations decreased by 6.0% from 342.3 in 2008 to 321.6 in 2018. The rate of MethHF hospitalization increase more than doubled that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold versus 3.48-fold, P <0.001). Annual inflation–adjusted hospitalization charges because of MethHF increased by 840% from $41.5 million in 2008 to $390.2 million in 2018, as compared with an 82% increase for all HF hospitalization from $3.503 billion to $6.376 billion. Patients with MethHF were significantly younger (49.64±10.06 versus 72.20±14.97 years old, P <0.001), predominantly male (79.1% versus 52.4%, P <0.001), with lower Charlson Comorbidity Index, yet they had longer length of stay, more hospitalizations per patient, and more procedures performed during their stays. CONCLUSIONS: MethHF hospitalizations increased sharply during the study period and contributed significantly to the HF hospitalization burden in California. This emerging HF phenotype, which engenders considerable financial and societal costs, calls for an urgent and concerted public health response to contain its spread.

LETHAL CONCENTRATION 50% OF PATCHOULI OIL (Pogostemon cablin) TOWARDS ZEBRAFISH EMBRYO (Danio rerio)

2020 ◽  
Vol 3 (2) ◽  
pp. 1
Author(s):  
Romel Ciptoadi Wijaya
Keyword(s):  
Danio Rerio ◽  
Zebrafish Embryo ◽  
Toxicity Testing ◽  
Positive Control ◽  
Negative Control ◽  
Lethal Concentration ◽  
Zebrafish Embryos ◽  
Treatment Groups ◽  
Precise Prediction ◽  
Loss Of Appetite

Preface :Patchouli Oil requires toxicity testing for safety before we can use it widely. It causes side effects such as nausea, vomiting and loss of appetite in some people. Determination of lethal concentration 50% (LC50) in the early stages of zebrafish embryos development will provide an easier, faster and precise prediction of toxicity. At a certain dose, it can cause impairment and death toward organisms. Therefore, the aim of this study was to determine LC50 of Patchouli Oil in carboximethyl cellulose emulsifier towards zebrafish embryo (Danio rerio).Method :Laboratory experimental study was using zebrafish embryos at 2 hours post fertilization. The total of 160 embryos were used and divided into 8 groups, i.e.; Negative control (KN) was given the embryonic fluid, positive control 1 was given 5000 ppm of patchouli oil (KP1), positive control was given 5000 ppm of CMC (KP2), and 5 treatment groups, i.e.; concentration of 10 ppm (P1), 30 ppm (P2), 60 ppm (P3), 90 ppm (P4) and 120 ppm (P5) of Patchouli oil which was emulsified in CMC. The study was conducted with 3 times repetition. Data collection was done by calculating total of embryo’s deaths for each treatment at 24-72 hours of exposure. Data were analyzed using Regression Probit Analysis.Results :Mortality in the group of KN was 1.6%, KP1 was 98.3% and KP2 was 0%. Meanwhile in the treatment group of P1, P2, P3, P4 and P5 respectively were 0%, 5%, 10%, 25%, and 50%.Conclusion :Based on these results, Lethal Concentration 50% of Patchouli Oil in CMC emulsifier towards zebrafish embryo is 120 ppm.

scholarly journals Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Chanika D. Jayasinghe ◽  
Uthpala A. Jayawardena
Keyword(s):  
Herbal Medicine ◽  
Molecular Mechanisms ◽  
Zebrafish Embryo ◽  
Toxicity Testing ◽  
Toxicity Assessment ◽  
Scientific Data ◽  
Herbal Remedies ◽  
Laboratory Animals ◽  
Genetic Redundancy ◽  
Crude Extracts

Herbal remedies have been practiced by humans over centuries and therefore possess time-proven safety. However, it is imperative to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic leads. Use of laboratory animals such as rats, mice, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more contentious. Thus, possible alternative models entailing lower vertebrates such as zebrafish were introduced. The zebrafish embryotoxicity model is at the forefront of toxicology assessment due to the transparent nature of embryos, low cost, short cycle, higher fecundity, and genetic redundancy to the humans. Recently, its application has been extended to herbal toxicology. The present review intends to provide a comprehensive assembly of studies that applied the zebrafish embryo model for the assessment of herbal toxicity. A systematic literature survey was carried out in popular scientific databases. The literature search identified a total of 1014 articles in PubMed = 12, Scopus SciVerse® = 623, and Google Scholar = 1000. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). These studies have investigated the toxicity of 6 polyherbal formulae, 16 crude extracts, and more than 30 phytocompounds/isolated constituents using the zebrafish embryotoxicity model. Moreover, this model has explicated the teratogenic effects and specific organ toxicities such as the kidney, heart, and liver. Furthermore, in some studies, the molecular mechanisms underlying the toxicity of herbal medicine have been elucidated. This comprehensive collection of scientific data solidifies the zebrafish embryo model as an effective model system for studying toxicological effects of a broad spectrum of herbal remedies. Henceforth, it provides a novel insight into the toxicity assessment of herbal medicine.

Sign in / Sign up

Export Citation Format

Share Document