Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment

Chen, Ying-Hsin; Chang, Cheng‐Hsin; Wang, Yun-Hsin; Wen, Chi‐Chung; Chen, Yun-Chen; Hu, Sheng-Chuan; Yü, Dah‐Shyong; Chen, Yau‐Hung

doi:10.1002/bdrb.20292

Cited by 13 publications

(8 citation statements)

References 44 publications

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“…Furthermore, previous acute toxicity studies on NVK by Anbarasu et al (2011) revealed that the ethanolic extract of NVK did not show mortality and toxic signs up to 2000 mg/kg and supports its indication for various fevers such as dengue and chikungunya fever as it had antipyretic, anti-inflammatory, and analgesic activity in experimental mice models [22]. Furthermore, there were no adverse effects reported in the earlier clinical studies on NVK administration both in adults [23] and pediatric population [24][25][26]. Thus, the present study results are found to be in concordance with the in vivo animal and human data of previous studies.…”

Section: Discussionsupporting

confidence: 63%

Teratogenicity Testing of Siddha Formulation of Nilavembu Kudineer on Zebrafish (Danio Rerio) Embryo

Shanmugapriya¹,

Elansekaran

Ramamurthy

et al. 2019

Asian J Pharm Clin Res

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Objective: The aim of the study was to evaluate the teratogenic effect of Nilavembu Kudineer (NVK) by testing in zebrafish embryo (Danio rerio). Methods: The study consisted of 30 embryos/culture plate/dose concentration containing a series of diluted decoction of NVK ranging from 10 μg to 640 μg/ml, and the embryo development was monitored at specific time points. The parameters such as developmental abnormality and adverse events were monitored at 24 hourly intervals for 96 h. Results: The study results showed 100% hatching and survival of embryos with no significant abnormalities in the extension of study from 96 to 120 h post-fertilization examinations. Conclusion: NVK did not have teratogenic potential on testing it in various concentrations on zebrafish embryos validating its safety during pregnancy.

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Section: Discussionsupporting

confidence: 63%

Teratogenicity Testing of Siddha Formulation of Nilavembu Kudineer on Zebrafish (Danio Rerio) Embryo

Shanmugapriya¹,

Elansekaran

Ramamurthy

et al. 2019

Asian J Pharm Clin Res

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“… In relation to diclofenac exposure to zebrafish ( Danio rerio ), it was previously shown that actin organization and muscle fibre alignment are disturbed thereby inducing a malformed somite phenotype. Isocitrate dehydrogenase (id: 482), as part of the Krebs cycle, is very involved in energy metabolism and significantly decreased in abundance here. It has previously been suggested to play a role in antioxidant defence.…”

Section: Discussionmentioning

confidence: 99%

Redox proteomic analysis of mytilus edulis gills: effects of the pharmaceutical diclofenac on a non‐target organism

Jaafar

Coelho

Sheehan

2015

Drug Testing and Analysis

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Veterinary and human pharmaceuticals are an emerging category of chemical pollutants with potential to cause serious toxicity to non-target organisms. Filter-feeding aquatic organisms such as mussels are especially threatened. In this study, the blue mussel, Mytilus edulis, was exposed to two doses (0.2 mg/L and 1 mg/L) of the anti-inflammatory diclofenac. Effects on the gill, the principal feeding organ of mussels, were investigated. It was noted that, while no effect was evident on gill glutathione transferase or catalase activities, there was a tissue-specific increase in glutathione reductase activity and reduction in total protein thiol groups. Two dimensional electrophoresis was performed and some affected proteins identified by in-gel tryptic digestion and peptide mass fingerprinting. Of these, four unique proteins (caspase 3/7-4, heat-shock cognate protein 70, a predicted enolase-like protein, arginine kinase) were found to be oxidized whilst eight unique proteins (β-tubulin, actin, isocitrate dehydrogenase, arginine kinase, heavy metal-binding HIP, cytosolic malate dehydrogenase, proteasome subunit alpha type 2, Mg: bb02e05 (glyceraldehyde-3-phosphate dehydrogenase) and superoxide dismutase) were found to have altered abundance. In addition, bioinformatic analysis suggested putative identities for six hypothetical proteins which either were oxidized or decreased in abundance. These were; 78 kDa glucose-regulated protein precursor, α-enolase, calreticulin, mitochondrial H + -ATPase, palmitoyl protein thioesterase 1 and initiation factor 5a. It is concluded that diclofenac causes significant oxidative stress to gills and that this affects key structural, metabolic and stress-response proteins.

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“…The procedures for antibody labeling, F‐actin staining, whole mount in situ hybridization and cryosectioning have been described previously (Chen et al ., , ; Ding and Chen, ; Lee et al ., ). Aside from these methods, F59 (Hybridoma Bank, Iowa IA, USA) and rabbit polyclonal anti‐laminin (Sigma‐Aldrich) were used as primary antibodies, and myod (NM_131262) was used as a probe.…”

Section: Methodsmentioning

confidence: 97%

Perturbation of cytosolic calcium by 2‐aminoethoxydiphenyl borate and caffeine affects zebrafish myofibril alignment

Fong

Chen

et al. 2014

J of Applied Toxicology

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The objective of the current study was to investigate the effects of Ca(2+) levels on myofibril alignment during zebrafish embryogenesis. To investigate how altered cytoplasmic Ca(2+) levels affect myofibril alignment, we exposed zebrafish embryos to 2-aminothoxyldiphenyl borate (2-APB; an inositol 1,4,5-trisphosphate receptor inhibitor that reduces cytosolic Ca(2+) levels) and caffeine (a ryanodine receptor activator that enhances cytosolic Ca(2+) levels). The results demonstrated that the most evident changes in zebrafish embryos treated with 2-APB were shorter body length, curved trunk and malformed somite boundary. In contrast, such malformed phenotypes were evident neither in untreated controls nor in caffeine-treated embryos. Subtle morphological changes, including changes in muscle fibers, F-actin and ultrastructures were easily observed by staining with specific monoclonal antibodies (F59 and α-laminin), fluorescent probes (phalloidin) and by transmission electron microscopy. Our data suggested that: (1) the exposure to 2-APB and/or caffeine led to myofibril misalignment; (2) 2-APB-treated embryos displayed split and short myofibril phenotypes, whereas muscle fibers from caffeine-treated embryos were twisted and wavy; and (3) zebrafish embryos co-exposed to 2-APB and caffeine resulted in normal myofibril alignment. In conclusion, we proposed that cytosolic Ca(2+) is important for myogenesis, particularly for myofibril alignment.

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Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment

Cited by 13 publications

References 44 publications

Teratogenicity Testing of Siddha Formulation of Nilavembu Kudineer on Zebrafish (Danio Rerio) Embryo

Teratogenicity Testing of Siddha Formulation of Nilavembu Kudineer on Zebrafish (Danio Rerio) Embryo

Redox proteomic analysis of mytilus edulis gills: effects of the pharmaceutical diclofenac on a non‐target organism

Perturbation of cytosolic calcium by 2‐aminoethoxydiphenyl borate and caffeine affects zebrafish myofibril alignment

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