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.
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.
Authors: J M Rhoads; R A Argenzio; W Chen; L M Graves; L L Licato; A T Blikslager; J Smith; J Gatzy; D A Brenner Journal: Gastroenterology Date: 2000-01 Impact factor: 22.682
Authors: Benedito A Carneiro-Filho; Reinaldo B Oriá; Katie Wood Rea; Gerly A C Brito; Jun Fujii; Tom Obrig; Aldo A M Lima; Richard L Guerrant Journal: Nutrition Date: 2004-10 Impact factor: 4.008
Authors: Andrea Tramarin; Nicoletta Parise; Stefano Campostrini; Donald D Yin; Maarten J Postma; Ramon Lyu; Roberta Grisetti; Amedeo Capetti; Anna Maria Cattelan; Maria Teresa Di Toro; Antonio Mastroianni; Elena Pignattari; Valeria Mondardini; Guido Calleri; Enzo Raise; Fabrizio Starace Journal: Qual Life Res Date: 2004-02 Impact factor: 4.147
Authors: Oluma Y Bushen; John A Davenport; Afonso Bezerra Lima; Stephen C Piscitelli; Arejas J Uzgiris; Terezinha M J Silva; Roberio Leite; Margaret Kosek; Rebecca A Dillingham; Arlete Girao; Aldo A M Lima; Richard L Guerrant Journal: Clin Infect Dis Date: 2004-05-26 Impact factor: 9.079
Authors: Leigh Ann Burns-Naas; Stephanie Webber; Donald G Stump; Joseph F Holson; Lilit Masarjian; Mark Zorbas Journal: Regul Toxicol Pharmacol Date: 2003-12 Impact factor: 3.271
Authors: Manuel B Braga Neto; Carolina V Aguiar; Jamilly G Maciel; Bruna M C Oliveira; Jesus E Sevilleja; Reinaldo B Oriá; Gerly A C Brito; Cirle A Warren; Richard L Guerrant; Aldo A M Lima Journal: BMC Gastroenterol Date: 2010-08-11 Impact factor: 3.067