Liver detox

Kupffer cells are the liver-resident macrophages lining the sinusoids and are mostly known for their role of scavengers, as crucial keepers of organ integrity. But due to the many fundamental functions of the liver notably linked to detoxication, metabolism, protein synthesis, or immunology, Kupffer cells are exposed to a dynamic environment and constantly adapt themselves by modulating their gene and protein expressions. In this context, the characterization of these cells at steady-state and upon challenges may be limited by the classical microscopy or flow cytometry which allow for the use of only few selected markers...

Data on the bioactivation of Phosmet (Pho), a phthalimide-derived organophosphate pesticide (OPT), to the neurotoxic metabolite Phosmet-oxon (PhOx) in human are not available. The characterization of the reaction in single human recombinant CYPs evidenced that the ranking of the intrinsic clearances was: 2C18>2C19>2B6>2C9>1A1>1A2>2D6>3A4>2A6. Considering the average human hepatic content, CYP2C19 contributed for the great majority (60%) at relevant exposure concentrations, while CYP2C9 (33%) and CYP3A4 (31%) were relevant at high substrate concentration...

OBJECTIVE: The aim was to establish the morphofunctional changes of liver in the experimental cirrhosis. PATIENTS AND METHODS: Materials and methods: The research was conducted on 24 white male Wistar rats. Experimental cirrhosis of the liver was simulated by oral administration of CCl4 2 g/kg 2 times weekly for three months. From the selected fragments of the liver, histological specimens were done according to the conventional method and examined by light microscopy...

Diet is a major source of human exposure to polycyclic aromatic hydrocarbons (PAHs), of which benzo[a]pyrene (BaP) is the most commonly studied and measured. BaP has been considered to exert its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes whose activity can be modulated by cytochrome P450 oxidoreductase (POR), the electron donor to CYP enzymes. Previous studies showed that BaP-DNA adduct formation was greater in the livers of Hepatic Reductase Null (HRN) mice, in which POR is deleted specifically in hepatocytes, than in wild-type (WT) mice...

BACKGROUND The hepatotoxicity of Tripterygium wilfordii Hook. f. (TWHF) limits its clinic utilization. Qingluo Tongbi formula (QTF) was formulated based on a basic Chinese medicine theory. Previous studies have confirmed the safety and efficacy of QTF in treating rheumatoid arthritis. Therefore, we considered that TWHF could be detoxified based on its reasonable compatibility with QTF. We investigated the detoxicity mechanism of QTF in reducing the liver toxicity of TWHF. MATERIAL AND METHODS We used network pharmacology to determine the relevant metabolism targets of TWHF, focusing on the phase II metabolic enzymes uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1), UGT1A6, and UGT2B7...

Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to probe the roles of bioactivation and detoxication of environmental toxins and toxicants in hepatotoxicity. Moreover, idiosyncratic hepatoxicity remains a key barrier in the clinical development of drugs. The now vast Nrf2 field emerged in part from biochemical and molecular studies on chemical inducers of hepatic detoxication enzymes and subsequent characterization of the modulation of drug/toxicant induced hepatotoxicities in mice through disruption of either Nrf2 or Keap1 genes...

Copper is an essential micronutrient but its excess in the dietary can be toxic. Both copper deficiency and abundance can occur in natural conditions and can lead to pathological dysfunctions. Many of the toxic effects of copper, such as increased lipid peroxidation in cell membranes and DNA damage, are due to its role in the generation of oxygen free radicals. Copper is released into the environment by both natural sources and human activities and it can damage organisms and ecosystems. In the present work the effects of copper has been studied on Xenopus laevis, an interesting model organism, after three weeks of exposure at 1 mg/L of CuCl, concentration allowed in the water for human use...

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar (As2 S2 ), a mineral traditional Chinese medicine (TCM), is proved to have great therapeutic effects in clinic and has been widely used in China for hundreds of years. As one of the most popular realgar-containing TCMs, NiuHuangJieDu Tablets (NHJDT) is used as OTC (over-the-counter) drug in daily life for fever relieving, detoxicating, as well as cure of sore throat and gingival swelling. However, the safety of realgar and its-containing TCMs still remains unclear...

Kinetic properties of purified Clarias gariepinus glutathione transferase (CgGST) was studied in the presence of Ficoll 70, Polyethylene glycol (PEG) 6000, bovine serum albumin (BSA) and in dilute solution. This was done to mimic the cytosol thereby unraveling the actual mechanism of detoxication involving glutathione transferase (GST) in the crowded intracellular milieu. CgGST from the liver of Clarias gariepinus was purified to homogeneity by affinity chromatography on glutathione (GSH) - agarose. Initial-velocity study was performed by varying the concentrations of GSH at various fixed concentrations of 1-chloro-2,4-dinitrobenzene (CDNB) and vice-versa...

The environmental carcinogen benzo[a]pyrene (BaP) is presumed to exert its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. However, studies using the Hepatic Reductase Null (HRN) mouse model, in which cytochrome P450 oxidoreductase (POR), the electron donor to CYP enzymes, is deleted specifically in hepatocytes, have shown that loss of hepatic POR-mediated CYP function leads to greater BaP-DNA adduct formation in livers of these mice than in wild-type (WT) mice. Here, we used CRISPR/Cas9 technology to knockout (KO) POR expression in mouse hepatoma Hepa1c1c7 cells to create an in vitro model that can mimic the HRN mouse model...

INTRODUCTION AND OBJECTIVES: Acute liver failure (ALF) is a dramatic disorder requiring intensive care. MicroRNAs (miRNAs) have been identified to play important roles in ALF. This study was performed to identify miRNA-mRNA co-expression network after ALF to investigate the molecule mechanism underlying the pathogenesis of ALF. MATERIALS AND METHODS: The microarray dataset GSE62030 and GSE62029 were downloaded from Gene Expression Omnibus database. Overlapping differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified in liver tissues from patients with hepatitis B virus (HBV)-associated ALF in comparison with normal tissues from donors...

BACKGROUND: Toluene was an organic compound used in chemical and drug industries, the main source of toluene emissions from fires. To reduce and even eliminate toluene toxins in chemical component could be using detoxification by foods. AIM: This research aimed to calculate the intake of foods rich in CYP2E1 enzyme and glycine to improve toluene detoxification. METHODS: The type of research was a descriptive study. The subject of the study was 51 workers in Romokalisari Surabaya who had worked for more than or equal to 10 years...

BACKGROUND: Acetaminophen, the ubiquitous over-the-counter analgesic and antipyretic, is the most common drug used in intentional overdoses in the United States. Inadvertent self-poisoning is also a surprisingly common unintended consequence of acetaminophen misuse for pain management. OBJECTIVE: The primary goal of this naturalistic study was to substantiate outcomes that were previously described in other large cohorts of patients with acetaminophen overdoses...

For fasiglifam (TAK875) and its metabolites the substance-specific mechanisms of liver toxicity were studied. Metabolism studies were run to identify a putatively reactive acyl glucuronide metabolite. In vitro cytotoxicity and caspase 3/7 activation were assessed in primary human and dog hepatocytes in 2D and 3D cell culture. Involvement of glutathione (GSH) detoxication system in mediating cytotoxicity was determined by assessing potentiation of cytotoxicity in a GSH depleted in vitro system. In addition, potential mitochondrial liabilities of the compounds were assessed in a whole-cell mitochondrial functional assay...

OBJECTIVE: This study was designed to investigate whether the mice treated with triptolide (TP) could disrupt the liver immune homeostasis, resulting in the inability of the liver to eliminate the harmful response induced by lipopolysaccharide (LPS). In addition, we explored whether apoptosis and necroptosis played a critical role in the progression of the hepatotoxicity induced by TP-LPS co-treatment. METHODS: Female C57BL/6 mice were continuously administrated with two different doses of TP (250 μg/kg and 500 μg/kg) intragastrically for 7 days...

Egg yolk immunoglobulins (IgY), as nutraceutical supplement for therapeutic or prophylactic intervention, has been extensively studied. The effects of IgY on small molecular toxin-induced toxicity in animals is unclear. In the present study, the protection of highly purified and specific anti-AFB1 IgY against AFB1-induced genotoxicity and oxidative damage on the rat liver model were investigated. Our results revealed that AFB1 induced significant oxidative damage markers, as well as AFB1-induced protein expression in antioxidant, pro- and anti-apoptosis processes in rat liver...

Cytochrome P450 (P450) enzymes are involved in the metabolism of carcinogens, as well as drugs, steroids, vitamins, and other classes of chemicals. P450s also oxidize ethanol, in particular P450 2E1. P450 2E1 oxidizes ethanol to acetaldehyde and then to acetic acid, roles also played by alcohol and aldehyde dehydrogenases. The role of P450 2E1 in cancer is complex in that P450 2E1 is also induced by ethanol, P450 2E1 is involved in the bioactivation and detoxication of a number of chemical carcinogens, and ethanol is an inhibitor of P450 2E1...

The Chicken Egg Genotoxicity Assay (CEGA) demonstrated responsiveness to various DNA-reactive chemicals requiring metabolic activation, which implies broad bioactivation capability. To assess potential metabolic competence, expression profiles of metabolic genes in the embryo-chicken fetal liver were determined using microarray technology. Fertilized chicken eggs were injected under the CEGA protocol with vehicle (deionized water [DW]), the activation-dependent carcinogens, diethylnitrosamine (DEN), and N-nitrosodiethanolamine (NDELA) at doses producing no effect on survival...

Compared to single exposure, chemical mixtures might induce joint toxicity including additive, synergistic and antagonistic effects on both organisms and environment. Owing to the specific toxicity of oxidative stress and binding to proteins, lead (Pb) is generally recognized a non-essential and threatening heavy metal to animals and human. Paraquat (PQ) is a widely used herbicide in agriculture and can trigger oxidative stress as well as Pb. Little information was available about joint effects of the two chemicals on toxicological responses in organisms, especially in fish...

BACKGROUND: Diabetes, with an increased prevalence and various progressive complications, has become a significant global health challenge. The concrete mechanisms responsible for the development of diabetes still remain incompletely unknown, although substantial researches have been conducted to search for the effective therapeutic targets. This review aims to reveal the novel roles of Xenobiotic Nuclear Receptors (XNRs), including the Peroxisome Proliferator-Activated Receptor (PPAR), the Farnesoid X Receptor (FXR), the Liver X Receptor (LXR), the Pregnane X Receptor (PXR) and the Constitutive Androstane Receptor (CAR), in the development of diabetes and provide potential strategies for research and treatment of metabolic diseases...