Reproductive toxicity of the hydroethanolic extract of the flowers of Acmella oleracea and spilanthol in zebrafish: In vivo and in silico evaluation

2019 ◽  
Vol 39 (2) ◽  
pp. 127-146 ◽  
Author(s):  
GC de Souza ◽  
MD Viana ◽  
LDM Goés ◽  
BL Sanchez-Ortiz ◽  
GA da Silva ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Reproductive Toxicity ◽  
Teratogenic Effects ◽  
The North ◽  
Histopathological Evaluation ◽  
Males And Females ◽  
Oral Availability ◽  
Hydroethanolic Extract ◽  
F1 Generation

Hydroethanolic preparations of Acmella oleracea is used in the north of Brazil as a female aphrodisiac. Thus, the objective of this study was to evaluate the action of the hydroethanolic extract of Acmella oleracea (EHFAo) flowers (21.873 and 44.457 mg/kg) and spilanthol (3 mg/kg) administered orally on reproductive performance and effects on the embryonic development of zebrafish F1 generation. It was observed that in the groups in which males and females received EHFAo and spilanthol, the spawning was interrupted, whereas in the groups in which only the females were treated, spawning occurred during the 21 days. Thus, in the histopathological evaluation of the gonads, it was possible to observe that the percentage of mature cells in the spermatozoa and females was significantly reduced. Only the embryo groups in which parental generation was treated with EHFAo showed lethal and teratogenic effects. On the other hand, the parental groups treated with the spilanthol presented only the lethality. Spilanthol and some metabolites showed good oral availability and important toxicological properties. Thus, it is suggested that the treatment of parental generation of zebrafish with EHFAo and spilanthol caused severe changes in the gonads and on fertility. However, on the embryo, the most striking effects in the development were recorded in the groups in which the parental generation was treated with the EHFAo, while the spilanthol influenced the lethality of the embryos.

scholarly journals Acmella oleracea (L) R. K. Jansen Reproductive Toxicity in Zebrafish: An In Vivo and In Silico Assessment

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Gisele Custodio de Souza ◽  
Arlindo César Matias Pereira ◽  
Muller Duarte Viana ◽  
Adriana Maciel Ferreira ◽  
Ianna Dias Ribeiro da Silva ◽  
...  
Keyword(s):  
Embryonic Development ◽  
In Silico ◽  
Reproductive Toxicity ◽  
Control Group ◽  
The North ◽  
Significant Difference ◽  
Hydroethanolic Extract ◽  
Primary Compound ◽  
F1 Generation

The plant species Acmella oleracea L. is used in the north of Brazil for the treatment of a range of illnesses, such as tuberculosis, flu, cough, and rheumatism and as an anti-inflammatory agent; besides, hydroethanolic formulations with this species are popularly used as a female aphrodisiac agent. However, currently, there are no studies performed evaluating its effect on embryonic development. Hence, this research aimed to evaluate the effects of the hydroethanolic extract of A. oleracea (EHFAo) on the reproductive performance (parental) and embryonic development (F1 generation) of zebrafish, at concentrations of 50, 100, and 200 μg/L. Histopathology of parental gonads after 21 days of exposure to EHFAo reveals few alterations in the ovaries and testes, not impairing the reproduction; an increase of eggs deposition was observed in animals treated with EHFAo at the highest concentrations. Nevertheless, concerning the embryonic development of F1, teratogenic effects were observed including tail deformation, cardiac and yolk edema, scoliosis, and growth retardation; these alterations were more prominent in the groups born from progenitors exposed to the highest concentrations (100 and 200 μg/L.); but only the occurrence of yolk and cardiac edema had a statistically significant difference when compared to the control group. The chromatographic analysis shows that spilanthol (affinin) was the primary compound found in the EHFAo. Hence, in silico assessment was performed to evaluate the pharmacokinetic and toxicological properties of this molecule and 37 metabolites derived from it. Overall, our data show that the treatment caused no detrimental changes in progenitors regarding their gonads or fertility but caused some potentially teratogenic activity in embryos, which may be due to the action of spilanthol’s metabolites M3, M6, M7, M8, M16, M28, and M31.

scholarly journals Defatted Hydroethanolic Extract of Ammodaucus leucotrichus Cosson and Durieu Seeds: Antidiabetic and Anti-Inflammatory Activities

2020 ◽  
Vol 10 (24) ◽  
pp. 9147
Author(s):  
Imane Es-Safi ◽  
Hamza Mechchate ◽  
Amal Amaghnouje ◽  
Anna Calarco ◽  
Smahane Boukhira ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Fasting Blood Glucose ◽  
Diabetic Mice ◽  
North African ◽  
Glucose Levels ◽  
The North ◽  
Blood Glucose Levels ◽  
Anti Inflammatory ◽  
Hydroethanolic Extract ◽  
Inflammatory Effect

The seeds of Ammodaucus leucotrichus Cosson and Durieu have been used in the North African Sahara as a traditional medicine to treat diabetes. The present study investigates the antidiabetic, antihyperglycemic, and anti-inflammatory properties of the defatted hydroethanolic extract of Ammodaucus leucotrichus (DHEAM). The antidiabetic and the antihyperglycemic studies were assessed on alloxan-induced diabetic with orally administered doses of DHEAM (100 and 200 mg/kg). At the same time, its anti-inflammatory propriety was evaluated by measuring edema development in the Wistar rats paw induced with carrageenan. Treatment of diabetic mice with DHEAM for four weeks managed their high fasting blood glucose levels, improved their overall health, and also revealed an excellent antihyperglycemic activity. Following the anti-inflammatory results, DHEAM exhibited a perfect activity. HPLC results revealed the presence of seven molecules (chlorogenic acid, 3-p-coumaroylquinic acid, gallic acid, ferulic acid, myricetin, quercetin, luteolin). This work indicates that the DHEAM has an important antidiabetic, antihyperglycemic, and anti-inflammatory effect that can be well established as a phytomedicine to treat diabetes.

scholarly journals Superoxide Dismutase 1 Nanoparticles (Nano-SOD1) as a Potential Drug for the Treatment of Inflammatory Eye Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 396
Author(s):  
Alexander N. Vaneev ◽  
Olga A. Kost ◽  
Nikolay L. Eremeev ◽  
Olga V. Beznos ◽  
Anna V. Alova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Reproductive Toxicity ◽  
Clinical Problem ◽  
Eye Diseases ◽  
Therapeutic Modality ◽  
Side Reactions ◽  
Copper Zinc Superoxide Dismutase ◽  
Tissue Degeneration ◽  
Endogenous Antioxidant

Inflammatory eye diseases remain the most common clinical problem in ophthalmology. The secondary processes associated with inflammation, such as overproduction of reactive oxygen species (ROS) and exhaustion of the endogenous antioxidant system, frequently lead to tissue degeneration, vision blurring, and even blindness. Antioxidant enzymes, such as copper–zinc superoxide dismutase (SOD1), could serve as potent scavengers of ROS. However, their delivery into the eye compartments represents a major challenge due to the limited ocular penetration. This work presents a new therapeutic modality specifically formulated for the eye on the basis of multilayer polyion complex nanoparticles of SOD1 (Nano-SOD1), which is characterized by appropriate storage stability and pronounced therapeutic effect without side reactions such as eye irritation; acute, chronic, and reproductive toxicity; allergenicity; immunogenicity; mutagenicity even at high doses. The ability of Nano-SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with a model immunogenic uveitis—the inflammation of the inner vascular tract of the eye. It was shown during preclinical studies that topical instillations of Nano-SOD1 were much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as corneal and conjunctival edema, iris hyperemia, and fibrin clots. Moreover, Nano-SOD1 penetrates into interior eye structures more effectively than SOD itself and retains enzyme activity in the eye for a much longer period of time, decreasing inflammation and restoring antioxidant activity in the eye. Thus, the presented Nano-SOD1 can be considered as a potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.

Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets

2001 ◽  
Vol 20 (10) ◽  
pp. 533-550 ◽  
Author(s):  
V Ciaravino ◽  
T McCullough ◽  
A D Dayan
Keyword(s):  
Ex Vivo ◽  
Reproductive Toxicity ◽  
In Vivo Studies ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Baxter Healthcare ◽  
Safety Margins ◽  
Toxicology Assessment

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

scholarly journals In vivo antileishmanial activity and histopathological evaluation in Leishmania infantum infected hamsters after treatment with a furoxan derivative

2017 ◽  
Vol 95 ◽  
pp. 536-547 ◽  
Author(s):  
Letícia de Almeida ◽  
Thaís Gaban Passalacqua ◽  
Luiz Antonio Dutra ◽  
Jéssica N. Varonez da Fonseca ◽  
Rhayanne F. Queiroz Nascimento ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Antileishmanial Activity ◽  
Histopathological Evaluation

scholarly journals Toxicity and teratogenicity evaluation of hydroethanolic extract of momordica charantia fruit using zebrafish (DANIO RERIO) embryos model

2019 ◽  
Vol 10 (SPL1) ◽  
Author(s):  
Noor Izati Abd Aziz ◽  
Vikneswari Perumal ◽  
Suganya Murugesu ◽  
Qamar Uddin Ahmed ◽  
Bisha Fathamah Uzir ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Crude Extract ◽  
Momordica Charantia ◽  
Spinal Curvature ◽  
Zebrafish Embryos ◽  
Chemical Toxicity ◽  
Active Constituent ◽  
Hydroethanolic Extract ◽  
Danio Rerio Embryos

 The use of zebrafish vertebrate model in vivo analysis of the drug toxicity and efficacy, chemical toxicity, and safety is increasing in recent researches. Momordica charantia Linn (Cucurbitaceae) has been traditionally claimed for its many protective roles. However, the development of toxicity effect may cause morphological abnormalities by using an embryo of zebrafish (Danio Rerio) is unknown. Hence, this study was designed to determine the toxicity and teratogenic effect of hydroethanolic extract of M. charantia fruit using Zebrafish (Danio Rerio) embryos. The crude extract was prepared from the fruit of M. charantia using 80% hydroethanolic solvent. The zebrafish embryos were exposed to serial dilution of crude extract. The active constituent was analyzed using gas chromatography coupled with mass spectrophotometry (GC-MS) Momordica charantia Linn (Cucurbitaceae) has been widely commercialized based on traditional usage as an antidiabetic product. The current study has shown the toxic effects of the M.  charantia fruit extract on the developing zebrafish embryos, and the median lethal concentration (LC50) was calculated to be 725.90 mg/L at 48 hpt. The observed effects are dependent on the time of exposure and concentrations of the extract. At higher concentration, the extract causes some morphological defects such as less pigmentation, dented tail, spinal curvature, oedema, reduced hatchability, and growth retardation, that indicates the presence of toxicant(s). Based on the GC-MS profiling, some of the compounds identified in the hydroethanolic extract, such as propanedioic acid and glutamine, may have caused the teratogenic effects to the embryos. Further research on the M. charantia fruit's metabolites should be carried out prior to any nutraceutical or pharmaceutical application.

scholarly journals Evaluation of The Antioxidant, Antidiabetic and Immunomodulatory Activity of Cydonia oblonga Fruit Extract

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Fatma Zahra Sakhri ◽  
Sakina Zerizer ◽  
Chawki Bensouici
Keyword(s):  
Free Radicals ◽  
Cation Radical ◽  
Antidiabetic Activity ◽  
Immunomodulatory Activity ◽  
Ferrous Ions ◽  
Cydonia Oblonga ◽  
Innate Defense ◽  
Hydroethanolic Extract

Dietary natural antioxidant consumption can protect the human body from several diseases induced by free radicals. The aim of this study was to evaluate the antioxidant, antidiabetic and immunomodulatory properties of Cydonia oblonga fruit. For this; hydroethanolic extract of Cydonia oblonga fruit (HECO) was examined for antioxidant activity using DPPH free radical sc avenging, ABTS cation radical decolorization, Cupric reducing antioxidant capacity (CUPRAC), and Metal Chelating on ferrous ions activities. The inhibitory activity of the extract against α-glucosidase enzyme was also investigated. HECO was tested in vivo for the immunomodulatory activity on non-specific immunity by the carbon clearance test. The content of the nonenzymatic antioxidant reduced glutathione (GSH) in liver tissue of used mice was estimated. in vitro studies revealed that the HECO has an inhibitory concentration (IC50) value of 249.26 ± 3.75μg/mL, 117.34 ± 1.41 μg/ml for DPPH and ABTS scavenging activity respectively. As well as the ability to reduce cupric (167.17 ± 1.15μg/mL) and iron (Fe) (417.98 ± 48.82μg/mL). The extract showed antidiabetic activity as evidenced by its capacity to inhibit the α-glucosidase enzyme (IC50: 326.48 ± 18.56 µg/mL) near the acarbose (IC50: 275.98 ± 1.57 µg/mL) used as a positive control. In addition, our results showed that HECO at the concentration of 50 and 100 mg/kg significantly increased the clearance rate of carbon from the bloodstream concomitant with increased liberation of GSH from liver cells. This study demonstrates that HECO is effective in scavenging free radicals and can serve as potent antioxidants that provide potential treatment and prevention for diabetes with benefits on the innate defense system. Keywords: Antidiabetic, Antioxidant, Cydonia oblonga, Hydroethanolic extract, Phagocytic activity

scholarly journals Estudo experimental in vivo e in vitro de plantas medicinais nos processos de embriotoxicidade e teratogenicidade

2021 ◽  
Vol 10 ◽  
pp. 227-240
Author(s):  
Regineide Xavier Santos ◽  
Iara Pacheco Gomes Volejo
Keyword(s):  
Medicinal Plants ◽  
Web Of Science ◽  
Teratogenic Effects

Este trabalho tem como objetivo contribuir na compilação de artigos científicos sobre as plantas medicinais que possuem efeitos embriotóxicos e teratogênicos comprovados através de testes experimentais in vivo e in vitro. Foi realizado um levantamento nas bases de dados Medline, Pubmed, Web of Science, Cochrane, Biblioteca virtual em saúde, Lilacs e Scielo com os descritores, “Medicinal plants, embryotoxicity”; “Medicinal plants, Teratogenic effects”; “Medicinal plants, teratogenicity” e seus correspondentes em português: “Plantas medicinais, embriotoxicidade”; “Plantas medicinais, efeitos Teratogênicos”; “Plantas Medicinais Teratogenicidade”. Oito artigos de ensaios in vivo e quatro de in vitro e um que apresenta os dois ensaios, preencheram os critérios de inclusão e exclusão e foram selecionados para esta revisão. Destes, cinco foram realizados na América, um na Europa, três na África e dois na Ásia. Na maioria dos estudos in vivo o extrato da planta foi injetado no animal, observando assim seus efeitos. A partir deste estudo, foi verificado que as plantas podem apresentar algum tipo de efeito no processo embrionário, portanto, o consumo durante o estado gravidico deve ser avaliado por um profissional da área. Palavras-chave: Gestação. Planta medicinal. Embriotoxicidade. Teratogênico.

scholarly journals An Investigation into Marmot Migration in Grand Teton National Park

1996 ◽  
Vol 20 ◽  
pp. 78-82
Author(s):  
George Montopoli ◽  
Nick Visser ◽  
Hank Harlow
Keyword(s):  
National Park ◽  
Movement Patterns ◽  
Snow Melt ◽  
Marmota Flaviventris ◽  
Long Distance ◽  
The North ◽  
North Fork ◽  
Males And Females ◽  
Study Sites ◽  
Long Distance Movement

In 1994 and 1995, a high abundant winter snowfall at higher elevations appeared to result in long distance movement patterns by yellow-bellied marmot (Marmota flaviventris) over snow to lower, snowfree elevations where food was more available. As the snow melted and food became abundant, the marmots return to higher altitudes. In 1996, we continued to investigate the potential for migrational movements, by studying two study sites at different elevations in the North Fork of Cascade Canyon. Four marmots at each site were implanted with intraperitoneal tracking transmitters. Of eight marmots that were equipped with intraperitoneal transmitters, six demonstrated significant movements of greater than 0.5 km, one did not, and one most likely died as a result of predation before any movement could be observed. Of the six that demonstrated significant movements within the canyon, only one moved distances greater than 1 km. Marmots, after emerging from hibernation, migrated down canyon to snowfree areas as they become available. With progressive snow melt, most marmots move upward to higher elevations, but not to the extent originally expected. Instead, they moved to the first available habitat where food was obtainable, and other (dominant) marmots accepted their presence. This movement is exhibited in both males and females, yearlings and adults, and melanistic and normal colored marmots.

scholarly journals Sex-difference affects disease progression in the MRMT-1 model of cancer-induced bone pain

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 445
Author(s):  
Sarah Falk ◽  
Tamara Al-Dihaissy ◽  
Laura Mezzanotte ◽  
Anne-Marie Heegaard
Keyword(s):  
Mammary Cancer ◽  
Bone Pain ◽  
Pain Processing ◽  
Mammary Cells ◽  
In Vivo Models ◽  
Metastatic Bone Pain ◽  
Essential Parameter ◽  
Pain State ◽  
Males And Females

An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo, and are commonly used in both males and females. Here we demonstrate that compared to males, females have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias of the progression of the pain state.

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