Protective effects of alanyl-glutamine supplementation against nelfinavir-induced epithelial impairment in IEC-6 cells and in mouse intestinal mucosa

Neto, Manuel B. Braga; Oliveira, Bruna M C; Rodrigues, Raphael Silva; Noronha, Francisco Jose; Leitão, Renata F. C.; Brito, Gerly A.C.; Lima, Aldo A. M.; Guerrant, Richard L.; Warren, Cirle A.

doi:10.4161/cbt.22251

Cited by 15 publications

(7 citation statements)

References 35 publications

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“…In the present experiment, Gln supplementation increased the villi height of jejunum and reduced the crypts depth of jejunum and ileum. Braga-Neto’s experiment found that dietary supplemented with Ala-Gln increased the height of intestinal villi in mouse [14]. Our present results indicated that dietary Ala-Gln supplementation increased the villi height of duodenum and jejunum, decreased the crypt depth of jejunum and ileum, which was consistent with previous study.…”

Section: Discussionsupporting

confidence: 92%

Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets

Shen

Zhang

Lin

et al. 2016

Asian-Australas J Anim Sci

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ObjectiveThe study was to investigate the effects of alanyl-glutamine (Ala-Gln) and glutamine (Gln) supplementation on the intestinal mucosa barrier in piglets.MethodsA total of 180 barrows with initial weight 10.01±0.03 kg were randomly allocated to three treatments, and each treatment consisted of three pens and twenty pigs per pen. The piglets of three groups were fed with control diet [0.62% alanine (Ala)], Ala-Gln diet (0.5% Ala-Gln), Gln diet (0.34% Gln and 0.21% Ala), respectively.ResultsThe results showed that in comparison with control diet, dietary Ala-Gln supplementation increased the height of villi in duodenum and jejunum (p<0.05), Gln supplementation increased the villi height of jejunum (p<0.05), Ala-Gln supplementation up-regulated the mRNA expressions of epidermal growth factor receptor and insulin-like growth factor 1 receptor in jejunal mucosa (p<0.05), raised the mRNA expressions of Claudin-1, Occludin, zonula occludens protein-1 (ZO-1) and the protein levels of Occludin, ZO-1 in jejunal mucosa (p<0.05), Ala-Gln supplementation enlarged the number of goblet cells in duodenal and ileal epithelium (p<0.05), Gln increased the number of goblet cells in duodenal epithelium (p<0.05) and Ala-Gln supplementation improved the concentrations of secretory immunoglobulin A and immunoglobulin G in the jejunal mucosa (p<0.05).ConclusionThese results demonstrated that dietary Ala-Gln supplementation could maintain the integrity of small intestine and promote the functions of intestinal mucosa barriers in piglets.

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Section: Discussionsupporting

confidence: 92%

Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets

Shen

Zhang

Lin

et al. 2016

Asian-Australas J Anim Sci

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“…However, the limited solubility and poor stability hampered the application of Glu as a therapeutic for I-R injury. Aiming to solve this problem, alanine (Ala) was employed to enhance the stability and solubility of Glu in the form of alanyl-Glu dipeptide, which had previously been demonstrated to protect rats from hepatic I-R injury ( 17 ). Thus, in the current study, Ala-Gln was added to the C-terminal of the peptide in order to improve the activity and stability of the 7-mer peptide.…”

Section: Resultsmentioning

confidence: 99%

Protection of rat liver against hepatic ischemia-reperfusion injury by a novel selenocysteine-containing 7-mer peptide

Jiang

Pan

Cheng

et al. 2016

Molecular Medicine Reports

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Hepatic ischemia-reperfusion (I-R) injury causes acute organ damage or dysfunction, and remains a problem for liver transplantation. In the I-R phase, the generation of reactive oxygen species aggravates the injury. In the current study, a novel selenocysteine-containing 7-mer peptide (H-Arg-Sec-Gly-Arg-Asn-Ala-Gln-OH) was constructed to imitate the active site of an antioxidant enzyme, glutathione peroxidase (GPX). The 7-mer peptide which has a lower molecular weight, and improved water-solubility, higher stability and improved cell membrane permeability compared with other GPX mimics. Its GPX activity reached 13 U/µmol, which was 13 times that of ebselen (a representative GPX mimic). The effect of this GPX mimic on I-R injury of the liver was assessed in rats. The 7-mer peptide significantly inhibited the increase in serum hepatic amino-transferases, tissue malondialdehyde, nitric oxide contents, myeloperoxidase activity and decrease of GPX activity compared with I-R tissue. Following treatment with the 7-mer peptide, the expression of B-cell CLL/lymphoma-2 (Bcl-2) was significantly upregulated at the mRNA and protein level compared with the I-R group, as determined by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. By contrast, Bcl-2 associated X protein (Bax) was downregulated by the 7-mer peptide compared the I-R group. Histological and ultrastructural changes of the rat liver tissue were also compared among the experimental groups. The results of the current study suggest that the 7-mer peptide protected the liver against hepatic I-R injury via suppression of oxygen-derived free radicals and regulation of Bcl-2 and Bax expression, which are involved in the apoptosis of liver cells. The findings of the present study will further the investigation of the 7-mer peptide as an effective therapeutic agent in hepatic I-R injury.

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“…The rat small intestinal crypt epithelium cell line IEC-6 is non-transformed. And it was often used as a necrotizing enterocolitis model system and nutritional studies ( Braga-Neto et al, 2012 ; Ruthig and Meckling-Gill, 1999 ; Yan et al, 2018 ). The uptake, metabolism, and transport processes are observed in IEC-6 cells ( Said et al, 1997 ; Sanderson and He, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of PEDV infection in rat crypt epithelial cells

Chen

Cui

Wang

et al. 2020

Veterinary Microbiology

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Protective effects of alanyl-glutamine supplementation against nelfinavir-induced epithelial impairment in IEC-6 cells and in mouse intestinal mucosa

Cited by 15 publications

References 35 publications

Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets

Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets

Protection of rat liver against hepatic ischemia-reperfusion injury by a novel selenocysteine-containing 7-mer peptide

Identification and characterization of PEDV infection in rat crypt epithelial cells

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