NLRP3 inflammasome activation triggers severe inflammatory liver injury in N, N-dimethylformamide-exposed mice.

N,N-dimethylformamide (DMF) is a widely utilized chemical solvent with various industrial applications. Previous studies have indicated that the liver is the most susceptible target to DMF exposure, whereas the underlying mechanisms remain to be elucidated. This study aimed to investigate the role of NLRP3 inflammasome in DMF-induced liver injury in mice by using two NLRP3 inflammasome inhibitors, Nlrp3 mice, Nfe2l2 mice, and a macrophage-depleting agent.

Allyl methyl disulfide (AMDS) prevents N,N-dimethyl formamide-induced liver damage by suppressing oxidative stress and NLRP3 inflammasome activation.

N,N-dimethylformamide (DMF), a widely consumed industrial solvent with persistent characteristics, can induce occupational liver damage and pose threats to the general population due to the enormous DMF-containing industrial efflux and emission from indoor facilities. This study was performed to explore the roles of allyl methyl disulfide (AMDS) in liver damage induced by DMF and the underlying mechanisms. AMDS was found to effectively suppress the elevation in the liver weight/body weight ratio and serum aminotransferase activities, and reduce the mortality of mice induced by DMF.

The potential health risks of short-chain chlorinated paraffin: A mini-review from a toxicological perspective.

Short-chain chlorinated paraffins (SCCPs) are ubiquitously distributed in various environmental matrics due to their wide production and consumption globally in the past and ongoing production and use in some developing countries. SCCPs have been detected in various human samples including serum, milk, placenta, nail, and hair, and internal SCCP levels were found to be positively correlated with biomarkers of some diseases. While the environmental occurrence has been reported in a lot of studies, the toxicity and underlying molecular mechanisms of SCCPs remain largely unknown.

Diallyl disulfide ameliorates ethanol-induced liver steatosis and inflammation by maintaining the fatty acid catabolism and regulating the gut-liver axis.

Diallyl disulfide (DADS) has been suggested to possess hepatoprotection against alcoholic liver disease (ALD) by a couple of pilot studies, while the underlying mechanisms remain largely unknown. This study aimed to investigate the hepatoprotective effects of DADS against ethanol-induced liver steatosis and early inflammation by using the chronic-plus-binge mice model and cultured J774A.1 macrophages and AML12 hepatocytes.

Discovery of a naturally occurring broad-spectrum inhibitor against gut bacterial β-glucuronidases from .

Gut bacterial β-glucuronidases (GUS) play an important role in deconjugation of various -glucuronides, which are tightly linked with the drug-induced intestinal toxicity. Increasing evidence has indicated that inhibition of bacterial GUS could alleviate GUS-associated intestinal toxicity, but the potent and broad-spectrum inhibitors against multiple bacterial GUS have been rarely reported. This study aimed to find potent and broad-spectrum GUS inhibitors from .

Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver.

Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis.

Critical Roles of Kupffer Cells in the Pathogenesis of Alcoholic Liver Disease: From Basic Science to Clinical Trials.

Alcoholic liver disease (ALD) encompasses a spectrum of liver injury ranging from steatosis to steatohepatitis, fibrosis, and finally cirrhosis. Accumulating evidences have demonstrated that Kupffer cells (KCs) play critical roles in the pathogenesis of both chronic and acute ALD. It has become clear that alcohol exposure can result in increased hepatic translocation of gut-sourced endotoxin/lipopolysaccharide, which is a strong M1 polarization inducer of KCs.

[Chemical Constituents from Eucommia ulmoides].

Objective: To investigate the chemical constituents from the barks of Eucommia ulmoides.

Methods: After the reflux extraction of the barks of Eucommia ulmoides with 95% ethanol, and the ethyl acetate part was separated and purified by chromatographic methods, such as silica gel, Sephadex LH-20, and ODS C18. The structures of isolated compounds were elucidated with modern spectral methods.

Associations between the tumor necrosis factor-α gene and interleukin-10 gene polymorphisms and risk of alcoholic liver disease: A meta-analysis.

Background: The critical roles of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the pathogenesis of alcoholic liver diseases (ALD) suggest that functional variations in the TNF-α (TNFA) and IL-10 genes may be related to individual susceptibility to ALD. As available studies examining the associations between TNFA or IL-10 polymorphisms and ALD risk have yielded conflicting results, a meta-analysis was conducted to clarify the potential relation between TNFA and IL-10 polymorphisms and the risk of ALD.

Methods: A comprehensive literature search was conducted to identify relevant studies.

Design, synthesis, and biofunctional evaluation of novel pentacyclic triterpenes bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety as antiproliferative agents.

A series of pentacyclic triterpenoids derivatives bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety has been synthesized and investigated for their potential antiproliferative activities. Pentacyclic triterpenoids derivative compounds were synthesized by a four or six step synthetic procedure. The activity studies were evaluated using Cell Counting Kit-8 method, and Western blotting analysis on A549 cells, MCF-7 cells and Hela cells.

The Role of NF mRNA and Calpain in NF Reduction of Acrylamide Neuropathy.

The purpose of this study was to study the role of neurofilament (NF) mRNA and calpain in NF reduction of acrylamide (ACR) neuropathy. Male Wistar adult rats were injected i.p.

Garlic Oil Suppressed Nitrosodiethylamine-Induced Hepatocarcinoma in Rats by Inhibiting PI3K-AKT-NF-κB Pathway.

To explore the underlying mechanisms for the protective effects of garlic oil (GO) against nitrosodiethylamine (NDEA)-induced hepatocarcinoma, 60 male Wistar rats were randomized into 4 groups (n=15): control group, NDEA group, and two GO plus NDEA groups. The rats in GO plus NDEA groups were pretreated with GO (20 or 40 mg/kg) for 7 days. Then, all rats except those in control group were gavaged with NDEA for 20 weeks, and the rats in GO plus NDEA groups were continuously administered with GO.

Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver.

Cytochrome P4502E1 (CYP2E1) has been demonstrated to play crucial roles in chronic ethanol-induced fatty liver, while its role in acute ethanol-induced fatty liver remains unclear. The current study was designed to evaluate the effects of chlormethiazole (CMZ), a specific inhibitor of CYP2E1, on acute ethanol-induced fatty liver, and to explore the mechanisms. Mice were pretreated with single dose of CMZ (50mg/kg body weight) by intraperitoneal injection or equal volume of saline, and then exposed to three doses of ethanol (5g/kg body weight, 25%, w/v) by gavage with 12h intervals.

CMZ reversed chronic ethanol-induced disturbance of PPAR-α possibly by suppressing oxidative stress and PGC-1α acetylation, and activating the MAPK and GSK3β pathway.

Background: Cytochrome P4502E1 (CYP2E1) has been suggested to play critical roles in the pathogenesis of alcoholic fatty liver (AFL), but the underlying mechanisms remains unclear. The current study was designed to evaluate whether CYP2E1 suppression by chlormethiazole (CMZ) could suppress AFL in mice, and to explore the underlying mechanisms.

Methods: Mice were treated with or without CMZ (50 mg/kg bw, i.

Pentoxifylline for the treatment of nonalcoholic fatty liver disease: a meta-analysis of randomized double-blind, placebo-controlled studies.

Aims: Pentoxifylline has been used to treat nonalcoholic fatty liver diseases (NAFLDs) due to its anti-tumor necrosis factor-α effects. We conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials to investigate the effect of pentoxifylline on the biochemical and histological parameters of NAFLD patients.

Materials And Methods: A comprehensive literature search was conducted in the database including PubMed, Embase, ISI web of knowledge, the Cochrane Library, and Google Scholar to identify randomized, double-blind, placebo-controlled clinical trials about the effects of pentoxifylline on NAFLD.

The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress.

Background: Diallyl disulfide (DADS) is a garlic-derived organosulfur compound. The current study is designed to evaluate the protective effects of DADS against ethanol-induced oxidative stress, and to explore the underlying mechanisms by examining the HO-1/Nrf-2 pathway.

Methods: We investigated whether or not DADS could activate the HO-1 in normal human liver cell LO2, and then evaluated the protective effects of DADS against ethanol-induced damage in LO2 cells and in acute ethanol-intoxicated mice.

Garlic oil suppressed the hematological disorders induced by chemotherapy and radiotherapy in tumor-bearing mice.

Although the anticancer effects of garlic and its products have been demonstrated by a variety of studies; however, few studies were conducted to investigate the effects of garlic on the adverse effects of chemo/radiotherapy. In order to clarify the above question and make a more comprehensive understanding of the anticancer effects of garlic, tumor xenograft mice model was established by subcutaneous injection of H22 tumor cells, and was used for the investigation of effects of garlic oil (GO) on the chemo/radiotherapy. In the chemotherapy test, tumor-bearing mice were treated with cyclophosphamide (CTX) or CTX plus GO (25 or 50 mg/kg bw) for 14 d, while the mice received a single 5 Gy total body radiation or radiation plus GO (25 or 50 mg/kg bw) in radiotherapy test.

Association between CD14-159C>T polymorphisms and the risk for alcoholic liver disease: a meta-analysis.

Aims: The association between CD14-159C>T polymorphisms and alcoholic liver disease (ALD) risk has been investigated in many studies, but the results were inconsistent. Therefore, we performed a meta-analysis to investigate the association between the CD14-159C>T polymorphisms and the risk for ALD.

Methods: A comprehensive literature search was conducted to identify the relevant studies from PubMed, ISI Web of Science, and Embase.

Garlic oil attenuated nitrosodiethylamine-induced hepatocarcinogenesis by modulating the metabolic activation and detoxification enzymes.

Nitrosodiethylamine (NDEA) is a potent carcinogen widely existing in the environment. Our previous study has demonstrated that garlic oil (GO) could prevent NDEA-induced hepatocarcinogenesis in rats, but the underlying mechanisms are not fully understood. It has been well documented that the metabolic activation may play important roles in NDEA-induced hepatocarcinogenesis.

Roles of cytochrome P4502E1 gene polymorphisms and the risks of alcoholic liver disease: a meta-analysis.

Background: Previous studies investigating the association between cytochrome P4502E1 (CYP2E1) polymorphisms and the risk of alcoholic liver diseases (ALD) have yielded conflicting results. Thus, a meta-analysis was performed to clarify the association between CYP2E1 polymorphisms and the risks of ALD.

Methods: A comprehensive literature search was conducted to identify the relevant studies.

The roles of garlic on the lipid parameters: a systematic review of the literature.

Garlic has long been the focus of experimental and clinical attentions due to its promising lipid-lowering effects. Numerous animal studies as well as in vitro ones have demonstrated the hypolipidemic effects of garlic, while clinical trials are highly inconsistent. Based on some double-blind, randomized, placebo-controlled clinical trials which denied the hypolipidemic effects of garlic, some meta-analysis concluded that garlic did not possess beneficial effects for hyperlipidemia.

PI3K/Akt pathway activation was involved in acute ethanol-induced fatty liver in mice.

Accumulating evidences support the important roles of sterol regulatory element-binding protein-1 (SREBP-1) activation in ethanol-induced fatty liver, but the underlying mechanisms for its activation are not fully understood. Recent studies have demonstrated that phosphatidylinositol 3 kinase (PI3K)/Akt pathway activation could enhance SREBP-1 activity. The current study was designed to investigate the potential roles of PI3K/Akt pathway in acute ethanol-induced fatty liver in mice.

Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats.

To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms.