scholarly journals Alteration of avian hepatic cytochrome P450 gene expression and activity by certain feed additives

2019 ◽  
Vol 67 (3) ◽  
pp. 418-429
Author(s):  
Orsolya Palócz ◽  
Géza Szita ◽  
György Csikó

We investigated the effect of four feed additives, namely β-glucan, a drinking water acidifier (DWA), a sanguinarine-containing product (SN) and fulvic acid, on hepatic cytochrome P450 (CYP) mRNA expression and CYP enzyme activity in chickens. The test substances were given to the chickens in the recommended dose or in tenfold dose. The administration of 5 mg/kg body weight (bw) β-glucan and 0.1 ml/kg bw DWA for five days decreased the relative gene expression of CYP1A4 and CYP2C23a. The dosing of 50 mg/kg bw β-glucan, 5 and 50 mg/kg bw SN, 1 ml/kg bw DWA and 250 mg/kg bw fulvic acid doubled the hepatic CYP1A4 activity. The activity of CYP2C and CYP3A remained unchanged. Avoidance of CYP1A-mediated feed-drug interactions requires accurate dosing of β-glucan, DWA and fulvic acid. According to our results, no treatment resulted in excessive or less CYP2C and CYP3A protein formation, which reduces the risk of potential feed additive-drug interactions in chickens. However, the administration of feed additive SN containing a plant alkaloid should be avoided concomitantly with CYP1A-metabolised medicines.

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Orsolya Palócz ◽  
Géza Szita ◽  
György Csikó

The intestinal epithelium is the first determining barrier to the drugs administered per os. Cytochrome P450 (CYP) enzymes are substantial in the initial step of xenobiotic metabolism; therefore, intestinal CYP enzyme activities could be an important influencing factor of the oral utilization of xenobiotic substances. In this study, the effect of four drinking water supplements on CYP mRNA levels of porcine intestinal epithelial cells was examined. Further goal of the study is to describe the effect of these feed additives on the proinflammatory response of the LPS-treated enterocytes. The nontransformed porcine intestinal epithelial cells (IPEC-J2) were grown on six-well polyester membrane inserts. Cell cultures were treated with LPS (10 μg/ml), β-glucan (5 and 50 μg/ml), sanguinarine-containing additive (5 and 50 μg/ml), drinking water acidifier (0.1 and 1 μl/ml), and fulvic acid (25 and 250 μg/ml) for 1 hour. Cells were washed with culture medium and incubated for additional 1 h before total RNA isolation. IL-6, IL-8, TNF-α, HSP70, CYP1A1, CYP1A2, and CYP3A29 mRNA levels were measured. The LPS treatment upregulated the gene expression of IL-8 and TNF-α. The relative gene expression of IL-6 remained unchanged and TNF-α and HSP70 were downregulated after the treatment with each feed additive. CYP1A1 and CYP1A2 expressions increased after sanguinarine-containing solution, fulvic acid, and drinking water acidifier treatment. None of the treatments changed the gene expression of CYP3A29, responsible for the metabolism of the majority of drug substances used in swine industry. The feed additive substances inhibited the expression of proinflammatory mediators HSP70 and TNF-α; however, β-glucan and fulvic acid elevated the production of the chemokine IL-8 mRNA in endotoxin-treated enterocytes. All acidic supplements increased the expression of CYP1A1 gene; their constituents may serve as a ligand of CYP1A1 nuclear receptors.


Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3940
Author(s):  
Ruimei Ling ◽  
Renyue Yang ◽  
Ping Li ◽  
Xiongfei Zhang ◽  
Tunkai Shen ◽  
...  

Asatone and isoasatone A from Asarum ichangense Cheng were determined to be defensive compounds to some insects in a previous investigation. However, the anti-insect activity mechanisms to caterpillar are still unclear. The compounds asatone and isoasatone A from A. ichangense were induced by Spodoptera litura. The anti-insect activity of asatone and isoasatone A to S. litura was further tested by weight growth rate of the insect through a diet experiment. Isoasatone A showed a more significant inhibitory effect on S. litura than asatone on the second day. The concentration of asatone was higher than isoasatone A in the second instar larvae of S. litura after 12 h on the feeding test diet. Both compounds caused mid-gut structural deformation and tissue decay as determined by mid-gut histopathology of S. litura. Furthermore, some detoxification enzyme activity were measured by relative expression levels of genes using a qPCR detecting system. Asatone inhibited the gene expression of the cytochrome P450 monooxygenases (P450s) CYP6AB14. Isoasatone A inhibited the relative expression levels of CYP321B1, CYP321A7, CYP6B47, CYP6AB14, and CYP9A39. Asatone increased the relative gene expression of the glutathione transferases (GSTs) SIGSTe1 and SIGSTo1, in contrast, isoasatone A decreased the relative gene expression of SIGSTe1 by about 33 fold. Neither compound showed an effect on acetylcholinesterase SIAce1 and SIAce2. The mechanism of anti-insect activity by both compounds could be explained by the inhibition of enzymes P450s and GSTs. The results provide new insights into the function of unique secondary metabolites asatone and isoasatone A in genus Asarum, and a new understanding of why A. ichangense is largely free of insect pests.


2006 ◽  
Vol 164 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Guobin Sun ◽  
Sheau-Fung Thai ◽  
Guy R. Lambert ◽  
Douglas C. Wolf ◽  
Douglas B. Tully ◽  
...  

2013 ◽  
Vol 20 (9) ◽  
pp. 1440-1448 ◽  
Author(s):  
Michael H. Kogut ◽  
Kenneth J. Genovese ◽  
Haiqi He ◽  
Christina L. Swaggerty ◽  
Yiwei Jiang

ABSTRACTWe have been investigating modulation strategies tailored around the selective stimulation of the host's immune system as an alternative to direct targeting of microbial pathogens by antibiotics. One such approach is the use of a group of small cationic peptides (BT) produced by a Gram-positive soil bacterium,Brevibacillus texasporus. These peptides have immune modulatory properties that enhance both leukocyte functional efficiency and leukocyte proinflammatory cytokine and chemokine mRNA transcription activitiesin vitro. In addition, when provided as a feed additive for just 4 days posthatch, BT peptides significantly induce a concentration-dependent protection against cecal and extraintestinal colonization bySalmonella entericaserovar Enteritidis. In the present studies, we assessed the effects of feeding BT peptides on transcriptional changes on proinflammatory cytokines, inflammatory chemokines, and Toll-like receptors (TLR) in the ceca of broiler chickens with and withoutS. Enteritidis infection. After feeding a BT peptide-supplemented diet for the first 4 days posthatch, chickens were then challenged withS. Enteritidis, and intestinal gene expression was measured at 1 or 7 days postinfection (p.i.) (5 or 11 days of age). Intestinal expression of innate immune mRNA transcripts was analyzed by quantitative real-time PCR (qRT-PCR). Analysis of relative mRNA expression showed that a BT peptide-supplemented diet did not directly induce the transcription of proinflammatory cytokine, inflammatory chemokine, type I/II interferon (IFN), or TLR mRNA in chicken cecum. However, feeding the BT peptide-supplemented diet primed cecal tissue for increased (P≤ 0.05) transcription of TLR4, TLR15, and TLR21 upon infection withS. Enteritidis on days 1 and 7 p.i. Likewise, feeding the BT peptides primed the cecal tissue for increased transcription of proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-18, type I and II IFNs) and inflammatory chemokine (CxCLi2) in response toS. Enteritidis infection 1 and 7 days p.i. compared to the chickens fed the basal diet. These small cationic peptides may prove useful as alternatives to antibiotics as local immune modulators in neonatal poultry by providing prophylactic protection againstSalmonellainfections.


2021 ◽  
Vol 11 (15) ◽  
pp. 7144
Author(s):  
Muriel C. Bischof ◽  
Sonja Häckel ◽  
Andrea Oberli ◽  
Andreas S. Croft ◽  
Katharina A. C. Oswald ◽  
...  

Increasing evidence implicates intervertebral disc (IVD) degeneration as a major contributor to low back pain. In addition to a series of pathogenic processes, degenerated IVDs become vascularized in contrast to healthy IVDs. In this context, angiopoietin (Ang) plays a crucial role and is involved in cytokine recruitment, and anabolic and catabolic reactions within the extracellular matrix (ECM). Over the last decade, a progenitor cell population has been described in the nucleus pulposus (NP) of the IVD to be positive for the Tie2 marker (also known as Ang-1 receptor). In this study, we investigated the influence of Ang-1 and Ang-2 on human NP cell (Tie2+, Tie2- or mixed) populations isolated from trauma patients during 7 days in normoxia (21% O2) or hypoxia (≤ 5% O2). At the end of the process, the proliferation and metabolic activity of the NP cells were analyzed. Additionally, the relative gene expression of NP-related markers was evaluated. NP cells showed a higher proliferation depending on the Ang treatment. Moreover, the study revealed higher NP cell metabolism when cultured in hypoxia. Additionally, the relative gene expression followed, with an increase linked to the oxygen level and Ang concentration. Our study comparing different NP cell populations may be the start of new approaches for the treatment of IVD degeneration.


1998 ◽  
Vol 151 (2) ◽  
pp. 294-310 ◽  
Author(s):  
Michael J. Santostefano ◽  
Xiaofeng Wang ◽  
Vicki M. Richardson ◽  
David G. Ross ◽  
Michael J. DeVito ◽  
...  

Author(s):  
D.L. Silva ◽  
B.R. Carvalho ◽  
H.C. Ferreira Júnior ◽  
H.C. Oliveira ◽  
C.R. Ferreira ◽  
...  

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