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

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

doi:10.3390/nu8030165

Cited by 17 publications

(16 citation statements)

References 46 publications

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“…Fish oil lipid emulsions have been shown to reduce acute kidney and acute lung injury, suppress inflammation, and favourably modulate immune function in septic mice 45–47. These emulsions consist of only fish oil, as opposed to Smoflipid, which contains 15% fish oil.…”

Section: Discussionmentioning

confidence: 99%

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock

et al. 2019

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IntroductionSepsis is a life-threatening, dysregulated response to infection. Both high-density lipoprotein and low-density lipoprotein cholesterol should protect against sepsis by several mechanisms; however, for partially unknown reasons, cholesterol levels become critically low in patients with early sepsis who experience poor outcomes. An anti-inflammatory lipid injectable emulsion containing fish oil is approved by the Food and Drug Administration as parenteral nutrition for critically ill patients and may prevent this decrease in serum cholesterol levels by providing substrate for cholesterol synthesis and may favourably modulate inflammation. This LIPid Intensive Drug therapy for Sepsis Pilot clinical trial is the first study to attempt to stabilise early cholesterol levels using lipid emulsion as a treatment modality for sepsis.Methods and analysisThis is a two-centre, phase I/II clinical trial. Phase I is a non-randomised dose-escalation study using a Bayesian optimal interval design in which up to 16 patients will be enrolled to evaluate the safest and most efficacious dose for stabilising cholesterol levels. Based on phase I results, the two best doses will be used to randomise 48 patients to either lipid injectable emulsion or active control (no treatment). Twenty-four patients will be randomised to one of two doses of the study drug, while 24 control group patients will receive no drug and will be followed during their hospitalisation. The control group will receive all standard treatments mandated by the institutional sepsis alert protocol. The phase II study will employ a permuted blocked randomisation technique, and the primary endpoint will be change in serum total cholesterol level (48 hours − enrolment). Secondary endpoints include change in cholesterol level from enrolment to 7 days, change in Sequential Organ Failure Assessment score over the first 48 hours and 7 days, in-hospital and 28-day mortality, lipid oxidation status, inflammatory biomarkers, and high-density lipoprotein function.Ethics and disseminationInvestigators are trained and follow good clinical practices, and each phase of the study was reviewed and approved by the institutional review boards of each institution. Results of each phase will be disseminated through presentations at national meetings and publication in peer-reviewed journals. If promising, data from the pilot study will be used for a larger, multicentre, phase II clinical trial.Trial registration numberNCT03405870.

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Section: Discussionmentioning

confidence: 99%

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock

et al. 2019

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“…In most of the studies, PUFA sources are fish or plants where the extraction procedures are complex and result in low yields of the product [ 59 , 60 , 64 , 65 ]. We decided to investigate the CO, due to its high levels of PUFA and potential for becoming an alternative source of these FAs [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Capybara Oil Improves Hepatic Mitochondrial Dysfunction, Steatosis, and Inflammation in a Murine Model of Nonalcoholic Fatty Liver Disease

Marinho

Vieira

Pereira

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of liver dysfunction worldwide and is commonly associated with obesity. Evidences suggest that NAFLD might be a mitochondrial disease, which contributes to the hepatic steatosis, oxidative stress, cytokine release, and cell death. Capybara oil (CO) is a rich source of polyunsaturated fatty acids (PUFA), which is known to improve inflammation and oxidative stress. In order to determine the effects of CO on NAFLD, C57Bl/6 mice were divided into 3 groups and fed a high-fat diet (HFD) (NAFLD group and NAFLD + CO group) or a control diet (CG group) during 16 weeks. The CO (1.5 g/kg/daily) was administered by gavage during the last 4 weeks of the diet protocol. We evaluated plasma liver enzymes, hepatic steatosis, and cytokine expression in liver as well as hepatocyte ultrastructural morphology and mitochondrial function. CO treatment suppressed hepatic steatosis, attenuated inflammatory response, and decreased plasma alanine aminotransferase (ALT) in mice with NAFLD. CO was also capable of restoring mitochondrial ultrastructure and function as well as balance superoxide dismutase and catalase levels. Our findings indicate that CO treatment has positive effects on NAFLD improving mitochondrial dysfunction, steatosis, acute inflammation, and oxidative stress.

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“…O ácido graxo poli-insaturado (Agpi) alfa linolênico ômega 3 (ω-3) é um ácido graxo essencial que não pode ser produzido pelo organismo humano (DUVALL;LEVY, 2016). Os Agpis ω-3 são encontrados primariamente em óleos de peixe (OP) e em plantas de coloração verde escura, e seus metabólitos são capazes de reduzir ou minimizar a criticidade de algumas patologias, como as cardiovasculares (MANZANARES;LANGLOIS;HARDY, 2016).…”

Section: Introductionunclassified

“…Também diminui a aderência e migração de neutrófilos e aumenta a velocidade em vênulas pós-capilares. Ainda, o OP altera os monócitos no sítio de inflamação, o que indica forte evidência do clearance apoptótico dos polimorfinucleares (PMN) em animais com sepse (KÖRNER et al, 2018).…”

Section: Introductionunclassified

“…Em um processo inflamatório e infeccioso ocorre desequilíbrio entre a produção de espécies reativas de oxigênio (Eros) e a de antioxidantes. A diferença entre as espécies reativas de oxigênio nos compartimentos teciduais e subcelulares contribui para a resposta ao estresse (GO et al, 2010). Vários fatores são responsáveis pelos Eros; na sepse cita-se o aumento das toxinas urêmicas associado à disfunção celular endotelial (YANG et al, 2012).…”

Section: Introductionunclassified

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Efeito Da Suplementação Com Óleo De Peixe No Modelo Experimental De Sepse

et al. 2020

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Introdução: A sepse é uma síndrome de grande prevalência, que causa altas morbidade e mortalidade. Terapêuticas adjuntas ao tratamento clínico convencional devem ser estudadas a fim de minimizar os efeitos da sepse. Objetivo: Investigar o efeito da suplementação com óleo de peixe (OP), rico em ômega-3, sobre as funções renal e pulmonar, a mortalidade e o estresse oxidativo de ratos com sepse. Metodologia: A sepse foi induzida por punção e ligadura cecal (CLP). O ômega (1 g/kg/dia, via oral) foi administrado, sete dias antes da CLP. Foram estudados os grupos Sham (CLP sem OP, n=10) e CLP+OP (suplementado com OP, n=10). Foram analisados o estresse oxidativo, e a histologia pulmonar e renal, quanto à sua estrutura e presença de polimorfinucleares (PMN), índice de edema pulmonar, função renal e sobrevida em 72 horas. Resultados: O estresse oxidativo não foi diferente para o grupo CLP +OP (p=0,06). A histologia, quanto à estrutura, evidenciou que o grupo suplementado com OP teve menor lesão estrutural, tanto no tecido pulmonar quanto no renal, entretanto, a contagem de polimorfinucleares (PMN) não foi diferente entre os grupos, para ambos os sistemas. O índice de edema pulmonar, embora menor no grupo CLP+OP, não foi significativamente diferente do encontrado no grupo Sham (p=0,59). Não houve alterações quanto à melhora da sobrevivência causada pela suplementação com OP. A função renal, estudada pela ureia e pela creatinina, não foi diferente entre os grupos. Conclusão: A suplementação com óleo de peixe (OP), neste estudo, não melhorou as condições renais, pulmonares e de mortalidade de ratos com sepse.

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

Cited by 17 publications

References 46 publications

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock

Capybara Oil Improves Hepatic Mitochondrial Dysfunction, Steatosis, and Inflammation in a Murine Model of Nonalcoholic Fatty Liver Disease

Efeito Da Suplementação Com Óleo De Peixe No Modelo Experimental De Sepse

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