Search

Introduction: Host defense peptides (HDPs) are increasingly referred to as promising candidates for the reduction of the use of conventional antibiotics, thereby combating antibiotic resistance. As HDPs have been described to exert various immunomodulatory effects, cecropin A (CecA) appears to be a potent agent to influence the host inflammatory response. Methods: In the present study, a chicken primary hepatocyte--non-parenchymal cell co-culture was used to investigate the putative immunomodulatory effects of CecA alone and in inflammatory conditions evoked by polyinosinicpolycytidylic acid (Poly I:C). To examine the viability of the cells, the extracellular lactate dehydrogenase (LDH) activity was determined by colorimetric assay. Inflammatory markers interleukin (IL)-8 and transforming growth factor-ß1 (TGF-ß1) were investigated using the ELISA method, whereas concentrations of IL-6, IL-10, and interferon-γ (IFN-γ) were assayed by Luminex xMAP technology. Extracellular H2O2 and malondialdehyde levels were measured by fluorometric and colorimetric methods, respectively. Results: Results of the lower concentrations suggested the safe application of CecA; however, it might contribute to hepatic cell membrane damage at its higher concentrations. We also found that the peptide alleviated the inflammatory response, reflected by the decreased production of the proinflammatory IL-6, IL-8, and IFN-γ. In addition, CecA diminished the levels of anti-inflammatory IL-10 and TGF-ß1. The oxidative markers measured remained unchanged in most cases of CecA exposure. Discussion: CecA displayed a multifaceted immunomodulatory but not purely anti-inflammatory activity on the hepatic cells, and might be suggested to maintain the hepatic inflammatory homeostasis in Poly I:C-triggered immune response. To conclude, our study suggests that CecA might be a promising molecule for the development of new immunomodulatory antibiotic-substitutive agents in poultry medicine; however, there is still a lot to clarify regarding its cellular effects. [ABSTRACT FROM AUTHOR]

Simple Summary: The inadequate use of antibiotics has resulted in the emergence of resistant microbes which imply a major threat in human and veterinary medicine. Therefore, natural alternatives improving the productivity of farm animals should be investigated to replace the extensive antibiotic application. The primary goal of the study was to prove the anti-inflammatory and antioxidant activity of luteolin (a common phytochemical of vegetables with a flavonoid structure) in a chicken hepatic cell culture. To investigate the effect of luteolin, a model was established which could recapitulate the Salmonella enterica serovar Typhimurium-induced hepatic inflammation of chickens. The inflammatory response was triggered with the elementary unit of the organ of bacterial motility, flagellin, and freshly isolated, primary hepatic cell cultures were applied containing both hepatocytes, the functional cells of the liver, and non-parenchymal, inflammatory cells. Luteolin at a concentration of 4 µg/mL did not alter the viability and the membrane integrity of the cells and therefore proved applicable to counteract flagellin. In combination with flagellin exposure, luteolin reduced the elevated IL-8 release of the cultured cells. Moreover, it reduced the concentration of IFN-α, H2O2 and malondialdehyde and restored the level of IL-10 and the ratio of IFN-γ/IL-10. In conclusion, luteolin had an anti-inflammatory and antioxidant effect in a chicken hepatic cell culture mimicking Salmonella enterica-associated inflammation. The use of natural feed supplements is an alternative tool to diminish the damage caused by certain bacteria, improving animal health and productivity. The present research aimed to investigate the proinflammatory effect of flagellin released from the bacterial flagellum of Salmonella enterica serovar Typhimurium and to attenuate the induced inflammation with luteolin as a plant-derived flavonoid on a chicken primary hepatocyte–non-parenchymal cell co-culture. Cells were cultured in a medium supplemented with 250 ng/mL flagellin and 4 or 16 µg/mL luteolin for 24 h. Cellular metabolic activity, lactate dehydrogenase (LDH) activity, interleukin-6, 8, 10 (IL-6, IL-8, IL-10), interferon-α, γ (IFN-α, IFN-γ), hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations were determined. Flagellin significantly increased the concentration of the proinflammatory cytokine IL-8 and the ratio of IFN-γ/IL-10, while it decreased the level of IL-10, indicating that the model served adequate to study inflammation in vitro. Luteolin treatment at 4 µg/mL did not prove to be cytotoxic, as reflected by metabolic activity and extracellular LDH activity, and significantly reduced the flagellin-triggered IL-8 release of the cultured cells. Further, it had a diminishing effect on the concentration of IFN-α, H2O2 and MDA and restored the level of IL-10 and the ratio of IFN-γ/IL-10 when applied in combination with flagellin. These results suggest that luteolin at lower concentrations may protect hepatic cells from an excessive inflammatory response and act as an antioxidant to attenuate oxidative damage. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to evaluate the effect of protected butyrate supplementation in broiler nutrition. Two experiments were conducted: (i) a performance study (1–35 days of age) and (ii) a study on the gut integrity and microbiome (1–21 days of age). The growth performance of birds, abundance of intestinal tight junction proteins, the quantitative characteristics of caecal microbiome and intestinal short chain fatty acid (SCFA) concentrations were investigated in these studies. Based on the results, it could be concluded that the addition of protected butyrate to broiler diets improved growth performance and intestinal integrity in accordance with the modulation of the caecal microbiome and the stimulated endogenous production of SCFA in the caecum. These findings provide important information that increases the understanding of the complex effects of the biologically most active SCFA, butyrate, on the overall health status and metabolism of the chicken. Short chain fatty acid (SCFA) butyrate has various beneficial effects on the gut microbiota as well as on the overall health status and metabolism of the host organism. The modulatory role of butyrate on gut barrier integrity reflected by tight junction protein expression has been already described in mammalian species. However, there is limited information available regarding chickens. Therefore, the main aim of this study was to monitor the effects of protected butyrate on claudin barrier protein and monocarboxylate transporter 1 abundance in different gastrointestinal segments of chickens as well as the growth performance of broiler chickens. The effect of protected butyrate on the caecal microbiota was monitored by quantifying the concentrations of total eubacteria and key enzymes of butyrate production. Furthermore, intestinal SCFA concentrations were also measured. Based on the data obtained, protected butyrate increased the overall performance as well as the barrier integrity of various gut segments. Protected butyrate also positively affected the SCFA concentration and composition. These findings provide valuable insight into the complex effects of protected butyrate on broiler gut health, highlighting the beneficial effects in improving intestinal barrier integrity and performance parameters. [ABSTRACT FROM AUTHOR]

The pancreatic secretion of insulin, a key endocrine regulator of metabolism and growth, can be greatly influenced by the gut-derived incretin hormones, namely by GIP (Glucose-dependent Insulinotropic Peptide) and GLP-1 (Glucagon-like Peptide 1). As insulin is a major stimulator of growth, affecting its producion may be of special importance in food-producing livestock. The aim of the present study was to investigate novel ways of modulating incretin and insulin homeostasis in chickens and rabbits by nutrition, e.g. by oral butyrate application, also studying the mechanisms of incretin action in both species as a comparative approach. Acute oral butyrate challenge significantly decreased plasma GIP levels by approx. 40% in both species: significant interactions of butyrate exposure and incubation time were found in both chickens (P = 0.038 and P = 0.034 at 30 and 60 min following butyrate ingestion [1.25 g/kg BW], respectively) and rabbits (P = 0.036 and P = 0.039 at 30 and 60 min after butyrate ingestion [0.25 g/kg BW], respectively), while plasma GLP-1, insulin and glucose concentrations remained unaffected by butyrate in both species over time. These results are in contrast to butyrate’s stimulating effect on both incretin and insulin secretion in mice, indicating specific, species-dependent differences even among mammalian species. Further, based on the analyzed correlations between the measured endocrine parameters (regardless of the butyrate exposure), it can be assumed that incretins may regulate pancreatic insulin release in rabbits on a partly different way compared to mice, humans and chickens. [ABSTRACT FROM AUTHOR]

The function of the transmembrane serine protease matriptase is well described in mammals, but it has not been elucidated in avian species yet. Hence, the aim of the present study was to assess the effects of the 3-amidinophenylalanine (3-AphA)-type matriptase inhibitors MI432 and MI460 on the inflammatory and oxidative state of chicken primary hepatocyte mono-cultures and hepatocyte–nonparenchymal cell co-cultures, the latter serving as a proper model of hepatic inflammation in birds. Cell cultures were exposed to MI432 and MI460 for 4 and 24 h at 10, 25, and 50 µM concentrations, and thereafter the cellular metabolic activity, extracellular interleukin (IL-)6, IL-8, H2O2 and malondialdehyde concentrations were monitored. Both inhibitors caused a transient moderate reduction in the metabolic activity following 4 h exposure, which was restored after 24 h, reflecting the fast hepatic adaptation potential to matriptase inhibitor administration. Furthermore, MI432 triggered an intense elevation in the cellular proinflammatory IL-6 and IL-8 production after both incubation times in all concentrations, which was not coupled to enhanced oxidative stress and lipid peroxidation based on unchanged H2O2 production, malondialdehyde levels and glutathione peroxidase activity. These data suggest that physiological matriptase activities might have a key function in retaining the metabolic and inflammatory homeostasis of the liver in chicken, without being a major modulator of the hepatocellular redox state. [ABSTRACT FROM AUTHOR]

Contamination of feed with mycotoxins has become a severe issue worldwide. Among the most prevalent trichothecene mycotoxins, T-2 toxin is of particular importance for livestock production, including poultry posing a significant threat to animal health and productivity. This review article aims to comprehensively analyze the pathological consequences, metabolism, and toxic effects of T-2 toxin in poultry. Trichothecene mycotoxins, primarily produced by Fusarium species, are notorious for their potent toxicity. T-2 toxin exhibits a broad spectrum of negative effects on poultry species, leading to substantial economic losses as well as concerns about animal welfare and food safety in modern agriculture. T-2 toxin exposure easily results in negative pathological consequences in the gastrointestinal tract, as well as in parenchymal tissues like the liver (as the key organ for its metabolism), kidneys, or reproductive organs. In addition, it also intensely damages immune system-related tissues such as the spleen, the bursa of Fabricius, or the thymus causing immunosuppression and increasing the susceptibility of the animals to infectious diseases, as well as making immunization programs less effective. The toxin also damages cellular processes on the transcriptional and translational levels and induces apoptosis through the activation of numerous cellular signaling cascades. Furthermore, according to recent studies, besides the direct effects on the abovementioned processes, T-2 toxin induces the production of reactive molecules and free radicals resulting in oxidative distress and concomitantly occurring cellular damage. In conclusion, this review article provides a complex and detailed overview of the metabolism, pathological consequences, mechanism of action as well as the immunomodulatory and oxidative stress-related effects of T-2 toxin. Understanding these effects in poultry is crucial for developing strategies to mitigate the impact of the T-2 toxin on avian health and food safety in the future. [ABSTRACT FROM AUTHOR]

Virus induced damage triggered by excessive inflammation and free radical production is a major threat in the poultry industry, leading to low productivity even in vaccinated flocks. The purpose of the study was to induce inflammation with the viral double-stranded RNA analog polyinosinic-polycytidylic acid (poly I:C) on chicken primary hepatocyte – non-parenchymal cell co-cultures to investigate the immunomodulatory and cell protectant effects of chicoric acid (CA) in comparison to N-acetylcysteine (NAC). Poly I:C significantly elevated the activity of the cell damage marker, lactate dehydrogenase (LDH) and the concentration of inflammatory cytokines (IL-6, IL-8, IFN-α, IFN-γ and M-CSF) in the culture medium and decreased cellular metabolic activity. CA significantly reduced the elevated LDH and cytokine levels in a dose-dependent manner, moreover, the higher (100 µg/mL) concentration of CA even elevated the level of metabolic activity. In contrast, 10 µg/mL NAC treatment decreased the level of each inflammatory cytokine but did not rectify cell damage or metabolic depression. The results indicate, that CA, present in common plants of the Asteraceae family, proves to be a beneficial hepatoprotective, and along with NAC, an immunomodulatory supplement in vitro under a stimulus mimicking viral infection. • Poly I:C induced elevation of cytokines on protein level in a chicken hepatic co-culture. • The cytokine production was in correlation with cell death independent of caspase-3. • Both the cytokine production and cell death could be alleviated by chicoric acid dose-dependently. • N-acetylcysteine could attenuate cytokine release although not the cytotoxic effect of poly I:C. [ABSTRACT FROM AUTHOR]