scholarly journals The Reproductive Toxicity Associated with Dodonaea viscosa, a Folk Medicinal Plant in Saudi Arabia

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Muhammad Farooq Khan ◽  
Ali S. Alqahtani ◽  
Omer M. Almarfadi ◽  
Riaz Ullah ◽  
Fahd A. Nasr ◽  
...  
Keyword(s):  
Medicinal Plant ◽  
Crude Extract ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Safety Data ◽  
Zebrafish Embryos ◽  
Hexadecanoic Acid ◽  
Dodonaea Viscosa ◽  
Experimental Animals

Dodonaea viscosa is a medicinal plant which is being used to treat various diseases in humans. The available safety data suggest that the plant does not produce any side effects, or toxicity, in tested adult experimental animals. However, the influence of D. viscosa on fetus or embryonic development is largely not known. This study was conducted in order to find out the reproductive toxicity of D. viscosa in experimental animals. Zebrafish embryos were used as the in vivo developmental toxicity animal model. Methanolic crude extract, hexane, chloroform, and butanol fractions were prepared from the leaves of D. viscosa. Zebrafish embryos were exposed to serial dilution of crude extract and other fractions. The crude extract and hexane fraction induced higher level of toxicity in zebrafish embryos as compared to chloroform and butanol fractions. The phenol and flavonoid estimation revealed that crude leaves extract and hexane fractions had lower content of phenol and flavonoid. Two major compounds, phytol and methyl ester, of hexadecanoic acid were identified by gas chromatography and mass spectrophotometry (GC-MS) analysis. More detailed studies are needed to check the toxicity of D. viscosa in pregnant experimental animals; however, the results from this study have shown that D. viscosa possesses reproductive toxicity and its use and doses must be carefully monitored in pregnant patients.

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.

Subchronic and Developmental Toxicity of Aromatic Extracts

2014 ◽  
Vol 33 (1_suppl) ◽  
pp. 136S-155S ◽  
Author(s):  
Walden E. Dalbey ◽  
Richard H. McKee ◽  
Katy Olsavsky Goyak ◽  
Jeffrey H. Charlap ◽  
Craig Parker ◽  
...  
Keyword(s):  
Aromatic Compounds ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Biologically Active ◽  
Toxicity Tests ◽  
Multiple Organs ◽  
Petroleum Fractions ◽  
Adverse Effect Level ◽  
Effect Level

Aromatic extracts (AEs; distillate AEs [DAEs] and residual AEs [RAEs]) are complex, highly viscous liquid petroleum streams with variable compositions derived by extraction of aromatic compounds from distillate and residual petroleum fractions from a vacuum distillation tower, respectively. The DAEs generally contain significant amounts of polycyclic aromatic compounds (PACs) and are carcinogenic. The RAEs typically contain lower concentrations of biologically active PACs. The PACs in refinery streams can cause effects in repeated-dose and developmental toxicity studies. In a 13-week dermal study, light paraffinic DAE had several dose-related effects involving multiple organs; no-observed-effect level was <5 mg/kg/d, with no overt toxicity. Predicted dose-responses at 10% (PDR10s), modeled doses causing a 10% effect on sensitive end points based on PAC content, ranged from 25 to 78 mg/kg/d for untested paraffinic DAEs. The no observed adverse effect level (NOAEL) for developmental toxicity for light paraffinic DAE was 5 mg/kg/d. Statistically significant developmental effects at higher doses were associated with maternal effects. The PDR10s for developmental toxicity of paraffinic DAEs ranged from 7 to >2000 mg/kg/d, reflecting differences due to variation in PACs. The NOAELs for RAEs were 500 mg/kg for 90-day studies and 2000 mg/kg for developmental toxicity. Reproductive toxicity is not considered to be a sensitive end point for AEs based on the toxicity tests with DAEs, RAEs, and other PAC-containing petroleum substances. In vivo micronucleus tests on heavy paraffinic DAE, RAEs, and a range of other petroleum substances have been negative. The exception to this general trend was a marginally positive response with light paraffinic DAE. Most DAEs are considered unlikely to produce chromosomal effects in vivo.

scholarly journals Silver Nanoparticles in Zebrafish (Danio rerio) Embryos: Uptake, Growth and Molecular Responses

2020 ◽  
Vol 21 (5) ◽  
pp. 1876
Author(s):  
Liyuan Qiang ◽  
Zeinab H. Arabeyyat ◽  
Qi Xin ◽  
Vesselin N. Paunov ◽  
Imogen J. F. Dale ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Body Length ◽  
Antimicrobial Agents ◽  
Developmental Toxicity ◽  
Defense Responses ◽  
Yolk Sac ◽  
Zebrafish Embryos ◽  
Continuous Exposure ◽  
Peroxisomal Membrane

Silver nanoparticles (AgNPs) are widely used in commercial applications as antimicrobial agents, but there have recently been increasing concerns raised about their possible environmental and health impacts. In this study, zebrafish embryos were exposed to two sizes of AgNP, 4 and 10 nm, through a continuous exposure from 4 to 96 h post-fertilisation (hpf), to study their uptake, impact and molecular defense responses. Results showed that zebrafish embryos were significantly impacted by 72 hpf when continuously exposed to 4 nm AgNPs. At concentrations above 0.963 mg/L, significant in vivo uptake and delayed yolk sac absorption was evident; at 1.925 mg/L, significantly reduced body length was recorded compared to control embryos. Additionally, 4 nm AgNP treatment at the same concentration resulted in significantly upregulated hypoxia inducible factor 4 (HIF4) and peroxisomal membrane protein 2 (Pxmp2) mRNA expression in exposed embryos 96 hpf. In contrast, no significant differences in terms of larvae body length, yolk sac absorption or gene expression levels were observed following exposure to 10 nm AgNPs. These results demonstrated that S4 AgNPs are available for uptake, inducing developmental (measured as body length and yolk sac area) and transcriptional (specifically HIF4 and Pxmp2) perturbations in developing embryos. This study suggests the importance of particle size as one possible factor in determining the developmental toxicity of AgNPs in fish embryos.

scholarly journals Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

2021 ◽  
Vol 22 (23) ◽  
pp. 12696
Author(s):  
Chloé Bars ◽  
Jente Hoyberghs ◽  
Allan Valenzuela ◽  
Laura Buyssens ◽  
Miriam Ayuso ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Culture Medium ◽  
Developmental Toxicity ◽  
Mammalian Species ◽  
Liver Microsomes ◽  
Zebrafish Embryos ◽  
Adult Zebrafish ◽  
Zebrafish Liver

The zebrafish (Danio rerio) embryo is gaining interest as a bridging tool between in-vitro and in-vivo developmental toxicity studies. However, cytochrome P450 (CYP)-mediated drug metabolism in this model is still under debate. Therefore, we investigated the potential of zebrafish embryos and larvae to bioactivate two known anti-epileptics, carbamazepine (CBZ) and phenytoin (PHE), to carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. First, zebrafish were exposed to CBZ, PHE, E-CBZ and HPPH from 5¼- to 120-h post fertilization (hpf) and morphologically evaluated. Second, the formations of E-CBZ and HPPH were assessed in culture medium and in whole-embryo extracts at different time points by targeted LC-MS. Finally, E-CBZ and HPPH formation was also assessed in adult zebrafish liver microsomes and compared with those of human, rat, and rabbit. The present study showed teratogenic effects for CBZ and PHE, but not for E-CBZ and HPPH. No HPPH was detected during organogenesis and E-CBZ was only formed at the end of organogenesis. E-CBZ and HPPH formation was also very low-to-negligible in adult zebrafish compared with the mammalian species. As such, other metabolic pathways than those of mammals are involved in the bioactivation of CBZ and PHE, or, these anti-epileptics are teratogens and do not require bioactivation in the zebrafish.

scholarly journals Analgesic and anti-inflammatory potential of Lupeol isolated from Indian traditional medicinal plant Crateva adansonii screened through in vivo and in silico approaches

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Thirumalaisamy Rathinavel ◽  
Subramanian Ammashi ◽  
Gnanendra Shanmugam
Keyword(s):  
Side Effects ◽  
Medicinal Plant ◽  
In Silico ◽  
Oral Route ◽  
Reference Standard ◽  
Leaf Extracts ◽  
Experimental Animals ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract Background Lupeol, a triterpene bioactive compound isolated from Indian traditional plant Crateva adansonii acted as promising and alternative anti-inflammatory agent to treatments of diseases related to inflammation. The inflammatory process in the body serves an important function in the control and repair of injury. However, it is self-perpetuating in number of disease conditions, which must be prevented and treated. Worldwide most prescribing NASID drug shows severe side effects. Whereas drug from natural origin shows dual inhibition of inflammatory and analgesic target protein with more efficacy and less side effects than NSAID drugs. Our study aims to isolate and screen the analgesic and anti-inflammatory potential of lupeol, a pentacyclic triterpenoid isolated from leaf extract of Crateva adansonii belongs to Capparaceae family commonly used Indian traditional medicine for treating inflammatory diseases. Results Methanol and chloroform leaf extracts (ME and CE) and lupeol fraction (LF) of plant Crateva adansonii is investigated through employing in vivo male Wistar albino rat model. Acute toxicity study of C. adansonii ME and CE leaf extracts reveals that no mortality and no behavioral changes in experimental animals up to 2 g/kg. So no lethal dose we consider two optimal doses 200 and 400 mg of plant leaf extracts for in vivo inflammatory and analgesic study. In vivo acute and chronic anti-inflammatory activity was carried out through carrageenan-induced rat paw edema and cotton pellet-induced granuloma models. LF (100 mg/kg, oral route) of Crateva adansonii evoked highest percentage of inflammation inhibition (50 and 33.96% respectively) in both in vivo acute and chronic inflammation model among all tested samples (ME and CE 200 mg and 400 mg/kg, oral route) including reference standard (10 mg/kg, oral route) indomethacin. Carrageenan-challenged experimental animals were screened for one inflammatory marker enzyme myeloperoxidase (MPO), inflammatory products such as Prostaglandrin E2 (PGE2), and eight different cytokines markers (TNFα, IL-6, IFN γ, IL-1α, IL-1β, MCP-1, Rantes, and MIP) associated with inflammation reveals that LF (100 mg/kg, oral route) of Crateva adansonii shows prominent anti-inflammatory activity than reference standard indomethacin (10 mg/kg, oral route) over all these biological tested parameters. In vivo analgesic assays such as hot plate assay and acetic acid-induced writhing assay revealed that LF (100 mg/kg, oral route) possesses significant analgesic activity (11.60 s and 69.05%) when compared with standard drug pentazocine(10 mg/kg, oral route). Finally, we made an in silico screening of lupeol against analgesic (nAChR) and anti-inflammatory (COX-2) target proteins reveals that lupeol possess highest binding affinity with nAChR and COX-2 target proteins (− 8.5 and − 9.0 Kcal/mol) over the reference standard pentazocine and indomethacin (− 7.0 and − 8.4 Kcal/mol) respectively. Conclusion The present study result provides a pharmacological evidences for analgesic and anti-inflammatory potential of lupeol isolated from Indian traditional plant Crateva adansonii act as a multi-target agent with immense anti-inflammatory potential targeting key molecules of inflammation such as MPO, PGE2, and eight pro-inflammatory cytokine markers. Outcome of present study is to find promising anti-inflammatory bioactive agents from the cheapest Indian traditional medicinal plant sources useful for pharmaceutical industries.

scholarly journals Corrigendum to “Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake”

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
James A. Edwards ◽  
Dirk Cremer
Keyword(s):  
Adverse Effects ◽  
Developmental Toxicity ◽  
Daily Intake ◽  
Safety Data ◽  
Safety Evaluation ◽  
Acceptable Daily Intake ◽  
Fetal Toxicity ◽  
Toxicological Data

Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which forms the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high-purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in cynomolgus monkeys at doses of 0.2 and 20 mg/kg  bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a two-generation study in rats, the NOAEL was 150 mg/kg  bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an acceptable daily intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission. Recent reevaluation of the data from the two-generation study indicated that the NOAEL should be redefined as the high dosage of 500 mg/kg bw/day, rather than the intermediate dosage of 150 mg/kg bw/day. The NOAEL of this study was formally amended to the high dosage. Also in 2018, JECFA raised the group ADI of lutein and zeaxanthin to “not specified,” due to the low toxicity of these substances.

scholarly journals Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
James A. Edwards
Keyword(s):  
Adverse Effects ◽  
Developmental Toxicity ◽  
Daily Intake ◽  
Safety Data ◽  
Safety Evaluation ◽  
Acceptable Daily Intake ◽  
Fetal Toxicity ◽  
Toxicological Data

Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series ofin vitroandin vivotests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission.

scholarly journals Evaluation of Noxious Effect of Environmental Contaminants Using Zebrafish Model

2020 ◽  
Vol 2 (1) ◽  
pp. 37
Keyword(s):  
Cell Death ◽  
Developmental Stages ◽  
Morphological Changes ◽  
Cell Damage ◽  
Developmental Toxicity ◽  
Environmental Pollutant ◽  
Toxicity Study ◽  
Zebrafish Embryos ◽  
Zebrafish Model

Effects of the inorganic chemicals Calcium Fluoride (CaF2) and Hexaflurosilicilic acid (H2SiF2) have been studied due to its excessive usage in drinking water plants, glass manufacturing etc. Toxicity studies on Zebrafish embryos have been carried out for CaF2 and H2SiF2 during the embryonic developmental stages to observe the changes taken place during the growth, development. These changes can be observed in cell differentiation, larval movements, delay in hatching, and by the changes in behavior. Due to the ease with the transparency of zebrafish embryos, it can be observed and manipulated. In the field of early developmental studies, these zebrafish embryos have been vital because they have faster development by which the whole organs get developed in 3 days. Thus it plays a significant role in the discovery and analysis of changes in the developmental aspects of their teratology study. Toxicity study in Adults Zebrafish can be studied through the histology analysis where the cell damage and cell death due to fluorides and acid ions which may also lead to morphological changes due to this environmental pollutant. This toxicity study can be studied based on behavioral effects, LC50 determination, and immunohistochemistry of the brain to observe the developmental neurotoxicity. This study describes the effect of the inorganic chemicals is leading to developmental toxicity, cell deformities, and cell death with the high mortality rate in the In vivo Zebrafish model.

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