Document Detail

Protective effects of alanyl-glutamine supplementation against nelfinavir-induced epithelial impairment in IEC-6 cells and in mouse intestinal mucosa.
MedLine Citation:
PMID:  22986234     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Human Immunodeficiency Virus (HIV) protease inhibitors (PI) remain a crucial component of highly active therapy (HAART) and recently have been demonstrated to have potent antitumor effect on a wide variety of tumor cell lines. However, discontinuation of therapy is an important issue, which may be related to various side-effects, especially diarrhea. The aim of this study was to evaluate the effects of nelfinavir (NFV), an HIV PI, and of alanyl-glutamine (AQ) supplementation, on intestinal cell migration, proliferation, apoptosis and necrosis, using IEC-6 cells and on intestinal crypt depth, villus length, villus area, mitotic index and apoptosis in Swiss mice.
METHODS: Migration was evaluated at 12 and 24 h after injury using a wound healing assay. Cellular proliferation was measured indirectly at 24 and 48 h using tetrazolium salt WST-1. Apoptosis and necrosis were measured by flow cytometry using the Annexin V assay. Intestinal morphometry and mitotic index in vivo were assessed following a seven-day treatment with 100 mg/kg of NFV, given orally. In vivo proliferation and apoptosis were evaluated by intestinal crypt mitotic index and immunohistochemistry, respectively.
RESULTS: In vitro, AQ supplementation enhanced IEC-6 cell migration and proliferation, following challenge with NFV. In vivo, AQ increased intestinal villus length, villus area, crypt depth and cell proliferation and cell migration, following treatment with NFV. AQ did not decrease cell death induced by NFV both in vivo and in vitro.
CONCLUSIONS: AQ supplementation is potentially beneficial in preventing the effects of PIs, such as NFV, in the intestinal tract.
Manuel B Braga-Neto; Bruna M C Oliveira; Raphael S Rodrigues; Francisco J Noronha; Renata F Leitao; Gerly A C Brito; Aldo A Lima; Richard L Guerrant; Cirle A Warren
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-17
Journal Detail:
Title:  Cancer biology & therapy     Volume:  13     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-01-09     Completed Date:  2013-06-26     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1482-90     Citation Subset:  IM    
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MeSH Terms
Apoptosis / drug effects*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Dipeptides / pharmacology*
Epithelial Cells / drug effects
HIV Protease Inhibitors / pharmacology
Intestinal Mucosa / drug effects*
Intestines / cytology,  drug effects,  pathology
Nelfinavir / pharmacology*
Wound Healing / drug effects
Grant Support
5 D43 TW006578/TW/FIC NIH HHS
Reg. No./Substance:
0/Dipeptides; 0/HIV Protease Inhibitors; HO3OGH5D7I/Nelfinavir; U5JDO2770Z/alanylglutamine

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