Zebrafish as a model to study inflammation: A tool for drug discovery

Belo, Marco Antônio de Andrade; Oliveira, Melque F.; Oliveira, Susana Luporini de; Aracati, Mayumi Fernanda; Rodrigues, Letícia Franchin; Costa, Camila Carlino da; Conde, Gabriel; Mendonça-Gomes, Juliana Moreira; Prata, Mariana Nathuê Lôbo; Barra, Alexandre de Almeida; Valverde, Thalita Marcolan; Melo, Daniela Chemim de; Eto, Silas Fernandes; Fernandes, Dayanne Carla; Romero, Marina G.M.C.; Júnior, José D. Corrêa; Silva, Juliana O.; Barros, André Luís Branco de; Perez, Andréa C.; Charlie-Silva, Ives

doi:10.1016/j.biopha.2021.112310

Cited by 30 publications

(20 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…in adult zebrafish induced abdominal edema and correlated protein expression of myeloid-specific peroxidase (Mpx), tumor necrosis factor-a (Tnfa), and nitric oxide synthase (iNos) as mediators of the inflammation ( 14 ). More recently, using a similar setting based on adult zebrafish stimulated for 4h with a high dose (3.5%) of λ-CGN and following a short transcriptomic approach, Belo et al., 2021, described the kinetics of the proinflammatory ( ilib , tnfa , nos2 , nrf2 ) gene expression ( 27 ). Besides, the same authors examined the histochemical activity of Tnfa, Il1b, Nos2, and Mhc2 proteins in the liver, spleen, and kidney of the fish treated with λ-CGN.…”

Section: Resultsmentioning

confidence: 99%

“…Adult male zebrafish individuals were fed, weighed, and injected with a λ-CGN, type IV (Cat. #22049; Sigma, USA) containing solution at 1.75 and 3.5% dissolved in PBS according to weight of each individual fish ( 27 ). Briefly, adult zebrafish contained in each test group were fed, sedated, and intraperitoneally (i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…Vertebrate animal models have proven their efficacy in screening inflammatory responses and determining specific molecular therapeutic targets in human medicine ( 23 – 25 ). In this context, zebrafish (ZF) emerged as an outstanding genetically tractable and practical model for screening the biological process of inflammation in vivo ( 26 , 27 ). Furthermore, this fish is a very versatile model organism.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts

et al. 2022

Self Cite

View full text Add to dashboard Cite

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae (Chondrus crispus) capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood. Here, we investigated the crucial factors behind the inflammatory milieu of λ-CGN-mediated inflammation administered at 0, 1.75, and 3.5% (v/w) by i.p. injection into the peritoneal cavity of adult zebrafish (ZF) (Danio rerio). We found that polymorphonuclear leukocytes (neutrophils) and lymphocytes infiltrating the ZF peritoneal cavity had short-term persistence. Nevertheless, they generate a strong pattern of inflammation that affects systemically and is enough to produce edema in the cavity. Consistent with these findings, cell infiltration, which causes notable tissue changes, resulted in the overexpression of several acute inflammatory markers at the protein level. Using reversed-phase high-performance liquid chromatography followed by a hybrid linear ion-trap mass spectrometry shotgun proteomic approach, we identified 2938 plasma proteins among the animals injected with PBS and 3.5% λ-CGN. First, the bioinformatic analysis revealed the composition of the plasma proteome. Interestingly, 72 commonly expressed proteins were recorded among the treated and control groups, but, surprisingly, 2830 novel proteins were differentially expressed exclusively in the λ-CGN-induced group. Furthermore, from the commonly expressed proteins, compared to the control group 62 proteins got a significant (p < 0.05) upregulation in the λ-CGN-treated group, while the remaining ten proteins were downregulated. Next, we obtained the major protein-protein interaction networks between hub protein clusters in the blood plasma of the λ-CGN induced group. Moreover, to understand the molecular underpinnings of these effects based on the unveiled protein sets, we performed a bioinformatic structural similarity analysis and generated overlapping 3D reconstructions between ZF and humans during acute inflammation. Biological pathway analysis pointed to the activation and abundance of diverse classical immune and acute phase reactants, several catalytic enzymes, and varied proteins supporting the immune response. Together, this information can be used for testing and finding novel pharmacological targets to treat human intestinal inflammatory diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has already been demonstrated that the formation of multinucleated giant cells and thus the foreign body reaction in teleost fishes is similar to those observed in mammals and that a granuloma includes epithelioid‐type cells and foreign body giant cells (Manrique et al, 2017; Secombes, 1985). Specifically, in the pacu, Piaractus mesopotamicus (Serrasalmidae), and the zebrafish, Danio rerio (Cyprinidae), implanted coverslips induced the formation of foreign body giant cells and Langhans' giant cells (Belo et al, 2005, 2021; Gurevich et al, 2020). Hence, our results support the assumption that the ricefish plug may be one of few examples of a stress‐induced evolutionary innovation (Hilgers et al, 2022; Wagner et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

How to stay attached—Formation of the ricefish plug and changes of internal reproductive structures in the pelvic brooding ricefish, Oryzias eversi Herder et al. (2012) (Beloniformes: Adrianichthyidae)

Schüller¹,

Vehof²,

Hilgers

et al. 2022

Journal of Morphology

View full text Add to dashboard Cite

Teleost fishes show an enormous diversity of parental care, ranging from no care to viviparity with maternal provisioning of embryos. External brooders carry their developing eggs attached to their bodies. This requires the formation of novel morphological structures to support attachment. The pelvic brooding ricefish Oryzias eversi evolved such a structure, called the "plug." The plug anchors attaching filaments from the fertilized eggs inside the female reproductive system, allowing the female to carry the embryos until hatching. Using histological sections and µcomputed tomography scanning, we show that the plug is formed by several types of interstitial cells, blood capillaries, and collagen fibrils that encapsulate the end of the attaching filaments in the anterior part of the gonoduct. Even 15 days after the loss of the protruding attaching filaments, the plug remains. In addition, the developed plug contains multinucleated giant cells that are derived from fusing macrophages. We thus hypothesize that the ricefish plug, which is vital for egg attachment in O. eversi, evolved due to an inflammatory reaction. We assume that it forms similar to a foreign body granuloma, as a reaction to irritation or injury of the gonoduct epithelium by the attaching filaments. Our study further corroborates that pelvic brooding entails a complex set of adaptations to prolonged egg-carrying in the female reproductive system. During brooding, for instance, ovulation in the ovary is suppressed and the anterior part of the gonoduct is characterized by an intricate, recessed folding.

show abstract

“…Thus, using zebrafish models offers an easy assessment of the molecular mechanisms of disease [ 25 ]. Additionally, the screening of the gene expression in disease conditions and the evaluation of anti-inflammatory compounds in zebrafish can be performed in a short time and a cost-effective manner [ 26 ]. On the other hand, mice lack or overexpress various genes involved in the immune response and rodents have limitations due to time, cost, and ethical constraints.…”

Section: Introductionmentioning

confidence: 99%

In Silico Study and Effects of BDMC33 on TNBS-Induced BMP Gene Expressions in Zebrafish Gut Inflammation-Associated Arthritis

et al. 2022

View full text Add to dashboard Cite

The bone morphogenic protein (BMP) family is a member of the TGF-beta superfamily and plays a crucial role during the onset of gut inflammation and arthritis diseases. Recent studies have reported a connection with the gut–joint axis; however, the genetic players are still less explored. Meanwhile, BDMC33 is a newly synthesized anti-inflammatory drug candidate. Therefore, in our present study, we analysed the genome-wide features of the BMP family as well as the role of BMP members in gut-associated arthritis in an inflammatory state and the ability of BDMC33 to attenuate this inflammation. Firstly, genome-wide analyses were performed on the BMP family in the zebrafish genome, employing several in silico techniques. Afterwards, the effects of curcumin analogues on BMP gene expression in zebrafish larvae induced with TNBS (0.78 mg/mL) were determined using real time-qPCR. A total of 38 identified BMP proteins were revealed to be clustered in five major clades and contain TGF beta and TGF beta pro peptide domains. Furthermore, BDMC33 suppressed the expression of four selected BMP genes in the TNBS-induced larvae, where the highest gene suppression was in the BMP2a gene (an eight-fold decrement), followed by BMP7b (four-fold decrement), BMP4 (four-fold decrement), and BMP6 (three-fold decrement). Therefore, this study reveals the role of BMPs in gut-associated arthritis and proves the ability of BDMC33 to act as a potential anti-inflammatory drug for suppressing TNBS-induced BMP genes in zebrafish larvae.

show abstract

Zebrafish as a model to study inflammation: A tool for drug discovery

Cited by 30 publications

References 48 publications

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts

How to stay attached—Formation of the ricefish plug and changes of internal reproductive structures in the pelvic brooding ricefish, Oryzias eversi Herder et al. (2012) (Beloniformes: Adrianichthyidae)

In Silico Study and Effects of BDMC33 on TNBS-Induced BMP Gene Expressions in Zebrafish Gut Inflammation-Associated Arthritis

Contact Info

Product

Resources

About