Health & Environmental Research Online (HERO)


PFHxS (355-46-4)


66 References Were Found:

Journal Article
Journal Article

Mouse Models for Atherosclerosis Research-Which Is My Line?

Authors: Oppi, S; Lüscher, TF; Stein, S (2019) Frontiers in Cardiovascular Medicine 6:46. [Review] HERO ID: 5926372

[Less] Atherosclerosis is one of the primary causes of cardiovascular disease and mortality. This chronic immunometabolic . . . [More] Atherosclerosis is one of the primary causes of cardiovascular disease and mortality. This chronic immunometabolic disease evolves during decades in humans and encompasses different organs and immune cell types, as well as local and systemic processes that promote the progression of the disease. The most frequently used animal model to study these atherogenic processes and inter-organ crosstalk in a short time frame are genetically modified mouse models. Some models have been used throughout the last decades, and some others been developed recently. These models have important differences in cholesterol and lipoprotein metabolism, reverse cholesterol transport pathway, obesity and diabetes as well as inflammatory processes. Therefore, the disease develops and progresses differently in the various mouse models. Since atherosclerosis is a multifaceted disease and many processes contribute to its progression, the choice of the right mouse model is important to study specific aspects of the disease. We will describe the different mouse models and provide a roadmap to facilitate current and future atherosclerosis researchers to choose the right model depending on their scientific question.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Mechanisms of environmental contributions to fatty liver disease

Authors: Wahlang, B; Jin, J; Beier, JI; Hardesty, JE; Daly, EF; Schnegelberger, RD; Falkner, KC; Prough, RA; Kirpich, IA; Cave, MC (2019) Current Environmental Health Reports 6:80-94. [Review] HERO ID: 5935661

[Less] PURPOSE: Fatty liver disease (FLD) affects over 25% of the global population and may . . . [More] PURPOSE: Fatty liver disease (FLD) affects over 25% of the global population and may lead to liver-related mortality due to cirrhosis and liver cancer. FLD caused by occupational and environmental chemical exposures is termed "toxicant-associated steatohepatitis" (TASH). The current review addresses the scientific progress made in the mechanistic understanding of TASH since its initial description in 2010.

RECENT FINDINGS: Recently discovered modes of actions for volatile organic compounds and persistent organic pollutants include the following: (i) the endocrine-, metabolism-, and signaling-disrupting chemical hypotheses; (ii) chemical-nutrient interactions and the "two-hit" hypothesis. These key hypotheses were then reviewed in the context of the steatosis adverse outcome pathway (AOP) proposed by the US Environmental Protection Agency. The conceptual understanding of the contribution of environmental exposures to FLD has progressed significantly. However, because this is a new research area, more studies including mechanistic human data are required to address current knowledge gaps.

Journal Article
Journal Article

Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH

Author: Pierantonelli I., Svegliati-Baroni G. (2019) 103:e1-e13. HERO ID: 5160096

[Less] Nonalcoholic fatty liver disease (NAFLD) represents a growing cause of chronic liver injury, especially . . . [More] Nonalcoholic fatty liver disease (NAFLD) represents a growing cause of chronic liver injury, especially in western countries, where it is becoming the most frequent indication for liver transplantation. Nonalcoholic fatty liver disease encompasses a spectrum of diseases that from simple steatosis (pure NAFLD) can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD and the mechanisms behind its progression to NASH have been extensively studied. However, although the processes that determine fat accumulation are mostly clear, the mechanisms associated with the progression of the disease are not fully characterized. In predisposed patients, lipid accumulation can promote lipotoxicity and mitochondrial dysfunction, thus triggering hepatocyte death, inflammation and fibrosis. The specific role of different lipids has been identified and free fatty acids as well as free cholesterol have been identified as toxic species. To make the picture more complex, the pathogenesis of NAFLD involves pathological connections between several organs, including the adipose tissue and the gut, with the liver. The "inflamed" adipose tissue plays a key role in the release of toxic lipids, whereas alterations in the gut-liver axis have been associated with the progression from NAFLD to NASH mediated by dysbiosis, alteration of intestinal barrier, and finally bacterial translocation, which can trigger proinflammatory and profibrogenetic pathways, finally leading to cirrhosis development.

Book/Book Chapter
Book/ Chapter

Chapter 11 - Urinary system

Authors: Khan, KNM; Hard, GC; Li, X; Alden, CL (2018) In Fundamentals of Toxicologic Pathology (Third Edition) (pp. 213-271). Cambridge, MA: Academic Press. HERO ID: 6296171

[Less] The urinary system is a common target site for toxicity of drugs and environmental chemicals. The kidney . . . [More] The urinary system is a common target site for toxicity of drugs and environmental chemicals. The kidney is particularly susceptible because of the high blood flow to this organ relative to its mass and the unique property of renal tubular epithelium in concentrating urine and its constituents including drugs and chemicals. Three main clinical entities in humans associated with drug effects on kidney are the nephrotic syndrome, acute renal failure (ARF), and chronic renal failure. It is estimated that about 20% of all ARF cases in humans are related to pharmaceutical agents and that 2% to 5% of patients admitted to the hospital will develop drug-induced acute renal insufficiency. An estimated 500,000 new patients exposed to drugs on a worldwide basis each year develop end-stage renal disease. The estimated annual costs of dialysis and transplants are substantial, representing a major challenge to the pharmaceutical and chemical industries for developing safer molecules.

The gold standard method for identification of toxicity to the urinary system is light microscopic examination, supplemented with renal function tests and biochemical markers of cell injury in blood and urine. To refine the risk assessment, establishment of the cellular and subcellular organelle targets of xenobiotic injury by the pathologist forms a cornerstone in expanding the mechanistic understanding of the injury process. Through identification of cellular and subcellular targets, the most sensitive biomarkers can be identified to noninvasively monitor for the presence of a specific xenobiotic insult in laboratory animals and eventually in humans. This chapter emphasizes the structural and biochemical changes and the potential mechanisms involved in urinary tract toxicity.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Authors: Kazankov, K; Jørgensen, S; Thomsen, K.L.; Møller, HJ; Vilstrup, H; George, J; Schuppan, D; Grønbæk, H (2018) Nature Reviews. Gastroenterology & Hepatology 16:145-159. HERO ID: 5932818

[Less] Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic . . . [More] Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH) are becoming the leading cause of liver-related morbidity and mortality worldwide, and a primary indication for liver transplantation. The pathophysiology of NASH is multifactorial and not yet completely understood; however, innate immunity is a major contributing factor in which liver-resident macrophages (Kupffer cells) and recruited macrophages play a central part in disease progression. In this Review, we assess the evidence for macrophage involvement in the development of steatosis, inflammation and fibrosis in NASH. In this process, not only the polarization of liver macrophages towards a pro-inflammatory phenotype is important, but adipose tissue macrophages, especially in the visceral compartment, also contribute to disease severity and insulin resistance. Macrophage activation is mediated by factors such as endotoxins and translocated bacteria owing to increased intestinal permeability, factors released from damaged or lipoapoptotic hepatocytes, as well as alterations in gut microbiota and defined nutritional components, including certain free fatty acids, cholesterol and their metabolites. Reflecting the important role of macrophages in NASH, we also review studies investigating drugs that target macrophage recruitment to the liver, macrophage polarization and their inflammatory effects as potential treatment options for patients with NASH.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Anti-Androgenic Effects in Rats

Authors: Ramhøj, L; Hass, U; Boberg, J; Scholze, M; Christiansen, S; Nielsen, F; Axelstad, M (2018) Toxicological Sciences 163:579-591. HERO ID: 4442260

[Less] The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread . . . [More] The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk.To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of twelve environmentally relevant endocrine disrupting chemicals (EDmix).Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS and two doses of PFHxS+EDmix (n = 5-7). Study 2 included control, 0.05, 5 or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5 or 25 mg PFHxS/kg plus EDmix (n = 13-20).PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused anti-androgenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate and vesicular seminalis.PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Lipotoxicity and the gut-liver axis in NASH pathogenesis

Authors: Marra, F; Svegliati-Baroni, G (2018) Journal of Hepatology 68:280-295. [Review] HERO ID: 5077865

[Less] The pathogenesis of non-alcoholic fatty liver disease, particularly the mechanisms whereby a minority . . . [More] The pathogenesis of non-alcoholic fatty liver disease, particularly the mechanisms whereby a minority of patients develop a more severe phenotype characterised by hepatocellular damage, inflammation, and fibrosis is still incompletely understood. Herein, we discuss two pivotal aspects of the pathogenesis of NASH. We first analyse the initial mechanisms responsible for hepatocellular damage and inflammation, which derive from the toxic effects of excess lipids. Accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity, and that specific lipid classes act as damaging agents on liver cells. In particular, the role of free fatty acids such as palmitic acid, cholesterol, lysophosphatidylcholine and ceramides has recently emerged. These lipotoxic agents affect the cell behaviour via multiple mechanisms, including activation of signalling cascades and death receptors, endoplasmic reticulum stress, modification of mitochondrial function, and oxidative stress. In the second part of this review, the cellular and molecular players involved in the cross-talk between the gut and the liver are considered. These include modifications to the microbiota, which provide signals through the intestine and bacterial products, as well as hormones produced in the bowel that affect metabolism at different levels including the liver. Finally, the activation of nuclear receptors by bile acids is analysed.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Pathophysiology of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis

Authors: Manne, V; Handa, P; Kowdley, KV (2018) Clinics in Liver Disease 22:23-37. [Review] HERO ID: 5431766

[Less] Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders ranging from hepatic . . . [More] Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH) and ultimately may lead to cirrhosis. Hepatic steatosis or fatty liver is defined as increased accumulation of lipids in hepatocytes and results from increased production or reduced clearance of hepatic triglycerides or fatty acids. Fatty liver can progress to NASH in a significant proportion of subjects. NASH is a necroinflammatory liver disease governed by multiple pathways that are not completely elucidated. This review describes the main mechanisms that have been reported to contribute to the pathophysiology of NAFLD and NASH.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Cytochrome P450 induction and xeno-sensing receptors pregnane X receptor, constitutive androstane receptor, aryl hydrocarbon receptor and peroxisome proliferator-activated receptor α at the crossroads of toxicokinetics and toxicodynamics

Authors: Hakkola, J; Bernasconi, C; Coecke, S; Richert, L; Andersson, TB; Pelkonen, O (2018) Basic and Clinical Pharmacology and Toxicology 123:42-50. [Review] HERO ID: 4933751

[Less] Pregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AHR) and . . . [More] Pregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AHR) and peroxisome proliferator-activated receptor (PPAR) are ligand-activated transcription factors that regulate expression of many xenobiotic-metabolizing enzymes including several cytochrome P450 (CYP) enzymes. Many xenobiotics induce CYP enzymes through these intracellular receptors and consequently affect toxicokinetics and possible metabolic activation of the receptor ligands and other xenobiotics utilizing similar metabolic pathways. However, it is now apparent that the xenobiotic receptors regulate also many endogenous functions and signalling pathways, and xenobiotic exposure thus may dysregulate an array of fundamental cell functions. This MiniReview surveys and discusses the multifaceted roles of xenobiotic receptors, for which CYP induction may serve as the first alert and possibly a biomarker for exposure to xenobiotics. With the current emergence of the adverse outcome pathway (AOP) concept, these receptors are being and will be assigned as molecular initiating events or key events in numerous discrete toxicity pathways.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

PXR: More than just a master xenobiotic receptor

Authors: Oladimeji, PO; Chen, T (2018) Molecular Pharmacology 93:119-127. [Review] HERO ID: 5161619

[Less] Pregnane X receptor (PXR) is a nuclear receptor considered to be a master xenobiotic receptor that coordinately . . . [More] Pregnane X receptor (PXR) is a nuclear receptor considered to be a master xenobiotic receptor that coordinately regulates the expression of genes encoding drug-metabolizing enzymes and drug transporters to essentially detoxify and eliminate xenobiotics and endotoxins from the body. In the past several years, the function of PXR in the regulation of xenobiotic metabolism has been extensively studied, and the role of PXR as a xenobiotic sensor has been well established. It is now clear, however, that PXR plays many other roles in addition to its xenobiotic-sensing function. For instance, recent studies have discovered previously unidentified roles of PXR in inflammatory response, cell proliferation, and cell migration. PXR also contributes to the dysregulation of these processes in diseases states. These recent discoveries of the role of PXR in the physiologic and pathophysiologic conditions of other cellular processes provides the possibility of novel targets for drug discovery. This review highlights areas of PXR regulation that require further clarification and summarizes the recent progress in our understanding of the nonxenobiotic functions of PXR that can be explored for relevant therapeutic applications.