Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection

Indexación ScopusSalmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens. © 2020, The Author(s).https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-020-00845-

Effects of anthocyanidins on myogenic differentiation and antioxidant defense in primary myogenic cells isolated from rainbow trout (Oncorhynchus mykiss)

There is increasing interest in using plant-derived extracts to promote growth and health in finfish species in recent years. Elucidating the effects of plant secondary metabolites on skeletal muscle growth signaling will contribute to an improved understanding of the effects of feeding carnivorous fish diets supplemented with plant extracts on fish somatic growth. Dietary intake of anthocyanins, a type of flavonoid widely distributed in plants, has long been associated with beneficial effects in both human and animal health; however, their effects in finfish are largely unknown. We conducted an experiment to test the effect of three doses (treatments A, B and C; 1. ×, 2.5. × and 10. ×, respectively) of a mixture of three types of anthocyanidins (peonidin, cyanidin and pelargonidin chloride) on the expression of several genes in primary myogenic cells isolated from the skeletal muscle of rainbow trout (Oncorhynchus mykiss) after 24. h of treatment. The genes of interest analyzed are involved in myogenic programing (pax7, myoD and myogenin), Notch signaling (her6 and hey2) and antioxidant enzymes (sod1, cat and gpx1). Significantly greater expression of pax7 in cells under treatment B compared with the untreated cells was detected. Although no differences in expression of myogenic regulatory factors, myoD and myogenin between test groups or the control were detected, a trend toward significantly lower expression in all groups tested compared with the control group was observed. Moreover, significantly higher expression levels of her6 and hey2 in cells under treatments A and B compared with untreated cells were detected. Although no significant differences in the expression of cat and sod1, significantly greater expression in gpx1 in all treated groups compared with the control group was detected. Collectively, we demonstrated that anthocyanidins enhance the expression of gpx1 in primary myogenic cells, thereby contributing to skeletal muscle tissue defense against oxidative stress in finfish species. Further, anthocyanidins appear to delay myogenic differentiation in primary myogenic cells by up-regulating the expression of pax7 while decreasing myogenic regulatory factors in a Notch signaling-dependent interaction. Whether this effect results a reduced growth performance and/or an increase in feed conversion ratio in fish fed diets supplemented with plant extracts rich in anthocyanins or anthocyanidins needs further study, and the need to better define the potential effects of different polyphenol classes in myogenic differentiation on primary myogenic cells from carnivorous fish is warranted. Statement of relevance: The study contributes to increase our understanding regarding the effect of plant-derived secondary metabolites such as anthocyanidins on myogenic program and antioxidant enzyme defense in differentiating myogenic cells from carnivorous fish. We have demonstrated that anthocyanidins may delay the progress of the myogenic differentiation process and promote antioxidant defense expression in myogenic cells. © 2015 Elsevier B.V

Effect of starvation on transcriptomes of brain and liver in adult female zebrafish (Danio rerio)

We used microarray and quantitative real-time PCR (qRT-PCR) analyses in adult female zebrafish (Danio rerio) to identify metabolic pathways regulated by starvation in the liver and brain. The transcriptome of whole zebrafish brain showed little response to 21 days of starvation. Only agouti-related protein 1 (agrp1) significantly responded, with increased expression in brains of starved fish. In contrast, a 21-day period of starvation significantly downregulated 466 and upregulated 108 transcripts in the liver, indicating an overall decrease in metabolic activity, reduced lipid metabolism, protein biosynthesis, proteolysis, and cellular respiration, and increased gluconeogenesis. Starvation also regulated expression of many components of the unfolded protein response, the first such report in a species other than yeast (Saccharomyces cerevisiae) and mice (Mus musculus). The response of the zebrafish hepatic transcriptome to starvation was strikingly similar to that of rainbow trout (Oncorhynchus mykiss) and less similar to mouse, while the response of common carp (Cyprinus carpio) differed considerably from the other three species