Yi J Zheng1, Yun K Tam, Ronald T Coutts. 1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Abstract
BACKGROUND: Apart from its benefits, parenteral nutrition (PN)-related complications have been reported. Studies have shown that PN could alter cytochrome P450 (CYP) activity. One of the possible mechanisms is through cytokine and nitrite release, which is triggered by endotoxin. The purpose of this study is to investigate the potential release of endotoxin, cytokines, and nitrite during PN. METHODS: Rats were randomly assigned into either (a) the PN group, which received continuous PN infusion only; or (b) the control group, which received normal chow with saline infusion. The infusions were administered continuously for 7 days, and then blood was collected and microsomes were prepared from the excised livers. RESULTS: Endotoxin levels in the PN group were significantly higher in portal vein but not in inferior vena cava when compared with those of the controls. TNF-alpha and IL-6 levels were significantly higher in the PN group (p < .05). However, IL-1 beta levels were not significantly different in the 2 groups (p > .05). The nitrite levels, the end product of nitric oxide formation, were found to be almost 2 times higher after PN (p < .05). CONCLUSIONS: It is confirmed that a 7-day infusion treatment of PN in rat may be linked to bacterial translocation, which leads to increased levels of endotoxin. This increase could trigger cytokine release, which could down regulate CYP activities.
BACKGROUND: Apart from its benefits, parenteral nutrition (PN)-related complications have been reported. Studies have shown that PN could alter cytochrome P450 (CYP) activity. One of the possible mechanisms is through cytokine and nitrite release, which is triggered by endotoxin. The purpose of this study is to investigate the potential release of endotoxin, cytokines, and nitrite during PN. METHODS:Rats were randomly assigned into either (a) the PN group, which received continuous PN infusion only; or (b) the control group, which received normal chow with saline infusion. The infusions were administered continuously for 7 days, and then blood was collected and microsomes were prepared from the excised livers. RESULTS: Endotoxin levels in the PN group were significantly higher in portal vein but not in inferior vena cava when compared with those of the controls. TNF-alpha and IL-6 levels were significantly higher in the PN group (p < .05). However, IL-1 beta levels were not significantly different in the 2 groups (p > .05). The nitrite levels, the end product of nitric oxide formation, were found to be almost 2 times higher after PN (p < .05). CONCLUSIONS: It is confirmed that a 7-day infusion treatment of PN in rat may be linked to bacterial translocation, which leads to increased levels of endotoxin. This increase could trigger cytokine release, which could down regulate CYP activities.
Authors: Maxime Nguyen; Gaëtan Pallot; Antoine Jalil; Annabelle Tavernier; Aloïs Dusuel; Naig Le Guern; Laurent Lagrost; Jean-Paul Pais de Barros; Hélène Choubley; Victoria Bergas; Pierre-Grégoire Guinot; David Masson; Belaid Bouhemad; Thomas Gautier Journal: Front Immunol Date: 2021-05-12 Impact factor: 7.561