ArticleShock (Augusta, Ga.)2018
On the Role of Illness Duration and Nutrient Restriction in Cholestatic Alterations that Occur During Critical Illness.
Article in Shock (Augusta, Ga.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill Children and the Impact of Delaying Parenteral Nutrition.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2018Trial
- Revisiting hypocholesterolemia during prolonged sepsis: From targeted cholesterol repletion to unresolved adrenal and muscle dysfunction.Molecular and cellular endocrinology · 2026Article
- Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines.Acute and critical care · 2024Article
- Critical illness-related corticosteroid insufficiency (CIRCI) - an overview of pathogenesis, clinical presentation and management.Frontiers in endocrinology · 2024Review
- Skeletal Muscle Myokine Expression in Critical Illness, Association With Outcome and Impact of Therapeutic Interventions.Journal of the Endocrine Society · 2023Article
- Efficacy and safety of ketone ester infusion to prevent muscle weakness in a mouse model of sepsis-induced critical illness.Scientific reports · 2022Article
- Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be.The Journal of clinical endocrinology and metabolism · 2022Review
- Pathophysiology of sepsis-induced cholestasis: A review.JGH open : an open access journal of gastroenterology and hepatology · 2022Review
- Identification of the toxic threshold of 3-hydroxybutyrate-sodium supplementation in septic mice.BMC pharmacology & toxicology · 2021Article
- The role of pro-opiomelanocortin in the ACTH-cortisol dissociation of sepsis.Critical care (London, England) · 2021Article
- [Effects of cholestasis and hypoxic hepatitis on prognosis of ICU patients: a retrospective study based on MIMIC Ⅲ database].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Induction of blood-circulating bile acids supports recovery from myelosuppressive chemotherapy.Blood advances · 2020Article
- Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsElevated markers of cholestasis are common in response to critical illness, and associated with adverse outcome. The role of illness duration and of nutrient restriction on underlying molecular pathways of such cholestatic responses have not been thoroughly investigated.
methodsIn a mouse model of surgery- and sepsis-induced critical illness, molecular pathways of cholestasis were investigated up to 7 days. To assess which changes are explained by illness-induced lack of feeding, nutrient-restricted healthy mice were studied and compared with ad libitum fed healthy mice. Furthermore, serum bile acid (BA) concentrations were quantified in 1,114 human patients with either short or long intensive care unit (ICU) stay, matched for type and severity of illness, up to ICU-day-7.
resultsIn critically ill mice, either evoked by surgery or sepsis, circulating and hepatic BA-levels progressively increased with time from day-3 onward, preceded by unsuppressed or upregulated CYP7A1 and CYP27A1 protein expression. From 30 h onward, nuclear farnesoid-X-receptor-retinoid-X-receptor staining was significantly suppressed in both critically ill groups, followed from day-3 onward by decreased gene expression of the apical exporter BA-specific export pump and increased expression of basolateral exporters multidrug resistance-associated protein 3 (MRP3) and MRP4. Nutrient restriction in healthy mice only partly mirrored illness-induced alterations in circulating BA and BA-transporters, without changing nuclear receptors or synthesis markers expression. Also in human critically ill patients, serum BA increased with time in long-stay patients only, similarly for patients with or without sepsis.
conclusionsCirculating BA concentrations rose days after onset of sepsis- and surgery-induced, critical illness, only partially explained by lack of feeding, preceded by suppressed nuclear feedback-sensors and ongoing BA synthesis. Expression of transporters suggested ongoing reversed BA-flow toward the blood.
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