Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

Juey-Ming Shih,Sung-Ling Yeh,Chiu-Li Yeh,Man-Hui Pai,Yu-Chen Hou,Yao-Ming Shih

doi:10.3390/nu8030165

Juey-Ming Shih, Sung-Ling Yeh + Show 4 more

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https://doi.org/10.3390/nu8030165

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Abstract

Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 0.05). Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05). Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05), at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

Highlights

Acute kidney injury (AKI) affects approximately 35% of all ICU patients
This study investigated the effects of Omegaven or SMOFlipid administered as a pharmaconutrient supplementation fed ad libitum after cecal ligation and puncture (CLP) on the development of AKI and associated inflammatory responses in a murine model of peritoneal sepsis
The findings showed that treatment with fish oil-based emulsion produced some changes in the T lymphocyte subsets and modulated the expression of kidney’s inflammatory mediators, both of which were not observed in septic mice treated with saline

Summary

Introduction

Acute kidney injury (AKI) affects approximately 35% of all ICU patients. This incidence correlates with an increase in in-hospital mortality from 20.9% to 56.8% depending on the severity of kidney injury [1]. Sepsis is the leading cause of AKI [2]. Septic patients have a greater risk of this developing into severe renal failure [3]. The pathogenesis of septic AKI is complex and multi-factorial. The host immune response in sepsis was considered to be initiated by a hyperinflammatory phase followed by a protracted immunosuppressive phase [4]

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