Transport, binding, and metabolism of sulfate conjugates in the liver

Pang, K. Sandy; Schwab, Andreas; Goresky, Carl A.; Chiba, Masato

doi:10.1016/0009-2797(94)90063-9

Cited by 29 publications

(16 citation statements)

References 64 publications

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“…P-cresol is presumably converted to PCS in the liver, which performs numerous sulfation reactions (28,29). Indican, for example, is produced by hepatic oxidation and sulfation of indole, which, like p-cresol, is made by gut bacteria.…”

Section: Discussionmentioning

confidence: 99%

Removal of P-Cresol Sulfate by Hemodialysis

Martinez

Recht

Hostetter

et al. 2005

Journal of the American Society of Nephrology

238

178

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Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. PCS and indican were 94 ؎ 1% and 93 ؎ 2% bound to plasma protein, respectively. Protein-binding caused a predictable decrease in measured dialytic clearance, which averaged 20 ؎ 4 ml/min for PCS and 25 ؎ 5 ml/min for indican as compared with 260 ؎ 20 ml/min for urea. Volumes of distribution for the protein-bound solutes were greater than the plasma volume, averaging 15 ؎ 7 L for PCS and 14 ؎ 3 L for indican as compared with 37 ؎ 7 for urea. Solute reduction ratios were 20 ؎ 9% for PCS, 30 ؎ 7% for indican, and 69 ؎ 5% for urea. We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS. PCS is poorly removed by hemodialysis because its clearance is limited by protein binding and the ratio of its volume of distribution to its clearance is high.

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Section: Discussionmentioning

confidence: 99%

Removal of P-Cresol Sulfate by Hemodialysis

Martinez

Recht

Hostetter

et al. 2005

Journal of the American Society of Nephrology

238

178

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“…Due to the specific anatomy of the hepatic sinusoids with lack of a basement membrane and the presence of fenestrae, extravascular substances such as albumin and sucrose are freely diffusible, establishing the pattern of flow-limited multiple dilution curves as opposed to the barrier-limited pattern (238). The technique allows calculating not only volumes of distribution, but also to study transport of hormones, drugs, organic and anorganic ions, bile acids, and metabolic substances (240,618,715,895).…”

Section: Multiple Indicator Dilution Techniquementioning

confidence: 99%

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Vollmar

Menger²

2009

Physiological Reviews

434

368

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The complex functions of the liver in biosynthesis, metabolism, clearance, and host defense are tightly dependent on an adequate microcirculation. To guarantee hepatic homeostasis, this requires not only a sufficient nutritive perfusion and oxygen supply, but also a balanced vasomotor control and an appropriate cell-cell communication. Deteriorations of the hepatic homeostasis, as observed in ischemia/reperfusion, cold preservation and transplantation, septic organ failure, and hepatic resection-induced hyperperfusion, are associated with a high morbidity and mortality. During the last two decades, experimental studies have demonstrated that microcirculatory disorders are determinants for organ failure in these disease states. Disorders include 1) a dysregulation of the vasomotor control with a deterioration of the endothelin-nitric oxide balance, an arterial and sinusoidal constriction, and a shutdown of the microcirculation as well as 2) an overwhelming inflammatory response with microvascular leukocyte accumulation, platelet adherence, and Kupffer cell activation. Within the sequelae of events, proinflammatory mediators, such as reactive oxygen species and tumor necrosis factor-alpha, are the key players, causing the microvascular dysfunction and perfusion failure. This review covers the morphological and functional characterization of the hepatic microcirculation, the mechanistic contributions in surgical disease states, and the therapeutic targets to attenuate tissue injury and organ dysfunction. It also indicates future directions to translate the knowledge achieved from experimental studies into clinical practice. By this, the use of the recently introduced techniques to monitor the hepatic microcirculation in humans, such as near-infrared spectroscopy or orthogonal polarized spectral imaging, may allow an early initiation of treatment, which should benefit the final outcome of these critically ill patients.

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“…This treatment also markedly altered the systemic metabolome, including reducing serum concentrations of toxic metabolites known to accumulate in the blood of patients with CKD (e.g., indoxyl sulfate, p-cresolsulfate) (135). Indole and p-cresol metabolites undergo O-sulfonation in the liver to enhance excretion and aid in detoxification (136). Excessive amounts of these metabolites may reduce the liver's capacity to detoxify other metabolites, as evidenced by a pharmacometabolomic study in humans that found that individuals with higher urinary concentrations of p-cresol sulfate had a reduced capacity to sulfonate the common drug acetaminophen (137).…”

Section: Df Kidney Function and Nitrogen Metabolismmentioning

confidence: 99%

Impact of Dietary Fibers on Nutrient Management and Detoxification Organs: Gut, Liver, and Kidneys

Kieffer

Martin

Adams

2016

Advances in Nutrition

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Increased dietary fiber (DF) intake elicits a wide range of physiologic effects, not just locally in the gut, but systemically. DFs can greatly alter the gut milieu by affecting the gut microbiome, which in turn influences the gut barrier, gastrointestinal immune and endocrine responses, and nitrogen cycling and microbial metabolism. These gut-associated changes can then alter the physiology and biochemistry of the body's other main nutrient management and detoxification organs, the liver and kidneys. The molecular mechanisms by which DF alters the physiology of the gut, liver, and kidneys is likely through gut-localized events (i.e., bacterial nitrogen metabolism, microbe-microbe, and microbe-host cell interactions) coupled with specific factors that emanate from the gut in response to DF, which signal to or affect the physiology of the liver and kidneys. The latter may include microbe-derived xenometabolites, peptides, or bioactive food components made available by gut microbes, inflammation signals, and gut hormones. The intent of this review is to summarize how DF alters the gut milieu to specifically affect intestinal, liver, and kidney functions and to discuss the potential local and systemic signaling networks that are involved. Adv Nutr 2016;7:1111-21.

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Transport, binding, and metabolism of sulfate conjugates in the liver

Cited by 29 publications

References 64 publications

Removal of P-Cresol Sulfate by Hemodialysis

Removal of P-Cresol Sulfate by Hemodialysis

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Impact of Dietary Fibers on Nutrient Management and Detoxification Organs: Gut, Liver, and Kidneys

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