Sex-, Age-, and Race/Ethnicity-Dependent Variations in Drug-Processing and NRF2-Regulated Genes in Human Livers.

Individual variations in xenobiotic metabolism affect the sensitivity to diseases. In this study, the impacts of sex, age, and race/ethnicity on drug-processing genes and nuclear factor erythroid 2-related factor 2 (NRF2) genes in human livers were examined via QuantiGene multiplex suspension array (226 samples) and quantitative polymerase chain reaction (qPCR) (247 samples) to profile the expression of nuclear receptors, cytochrome P450s, conjugation enzymes, transporters, bile acid metabolism, and NRF2-regulated genes. Sex differences were found in expression of about half of the genes, but in general the differences were not large.

LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice.

Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles.

Investigation of the differential transport mechanism of cinnabar and mercury containing compounds.

Background: Cinnabar has a long history of uses in Chinese traditional medicines as an ingredient in various remedies. However, the detailed mechanism of cinnabar in medication remains unclear, and the toxicity of cinnabar has been a debate due to its containing mercury sulfide. This study was designed to investigate the differential transport mechanism of cinnabar and other Hg-containing compounds HgCl, MeHg and HgS, and to determine if organic anion transporters OAT1 and OAT3 were involved in the differential transport mechanism.

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses.

Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2).

[Effect of Zuotai and HgS on gene expression of drug-metabolizing enzymes in livers of mice].

Zuotai and cinnabar(96%HgS) are contained in many traditional medicines. To examine their potential effects on drug metabolism genes, mice were orally given Zuotai or HgS at doses of 10, 30, 100, 300 mg•kg⁻¹ for 7 days. HgCl2(33.

A review of cinnabar (HgS) and/or realgar (AsS)-containing traditional medicines.

Ethnopharmocological Relevance: Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries.

Aim Of The Review: This review uses cinnabar (HgS) and realgar (AsS) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives.

Materials And Methods: A literature search on cinnabar and realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out.

Oeanolic acid protects against the hepatotoxicity of D-galactosame plus endotoxin in mice.

Oleanolic acid (OA) is a triterpenoid contained in many herbal medicines. The aim of this study was to investigate the protective effect of OA against D-galactosame plus lipopolysaccharides (D-GalN/LPS)-induced acute liver injury and the underling mechanisms. Mice were randomly divided into normal control with vehicles only (corn oil), D-GalN/LPS only (700mg/10μg/kg, ip), OA-po (200μmol/kg in corn oil, po) plus D-GalN/LPS, and OA-sc (50μmol/kg in 2% tween 80, sc) plus D-GalN/LPS groups.

Dendrobium nobile Lindl. alkaloids regulate metabolism gene expression in livers of mice.

Objectives: In our previous studies, Dendrobium nobile Lindl. alkaloids (DNLA) has been shown to have glucose-lowering and antihyperlipidaemia effects in diabetic rats, in rats fed with high-fat diets, and in mice challenged with adrenaline. This study aimed to examine the effects of DNLA on the expression of glucose and lipid metabolism genes in livers of mice.

Atorvastatin alters the expression of genes related to bile acid metabolism and circadian clock in livers of mice.

Aim: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice.

Dendrobium nobile Lindl alkaloid, a novel autophagy inducer, protects against axonal degeneration induced by Aβ in hippocampus neurons in vitro.

Aims: Axonal degeneration is a pathological symbol in the early stage of Alzheimer's disease (AD), which can be triggered by amyloid-β (Aβ) peptide deposition. Growing evidence indicates that deficit of autophagy eventually leads to the axonal degeneration. Our previous studies have shown that Dendrobium nobile Lindl alkaloid (DNLA) had protective effect on neuron impairment in vivo and in vitro; however, the underlying mechanisms is still unclear.

Dysregulation of metallothionein and circadian genes in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the major threat to human health, and disruption of circadian clock genes is implicated in hepatocarcinogenesis. This study examined the dysregulation of metallothioneins and circadian genes in achieved human HCC (n = 24), peri-HCC tissues (n = 24) as compared with normal human livers (n = 36). Total RNA was extracted and reverse transcribed.

Ontogeny, aging, and gender-related changes in hepatic multidrug resistant protein genes in rats.

Unlabelled: Multidrug resistance proteins (Mrps) are efflux transporters playing important roles in endogenous substances and xenobiotics transport out of the liver. Children, elderly, gender and physio-pathological conditions could influence their expression and result in changes in drug disposition.

Aim: This study was aimed to examine the development-, aging-, and sex-dependent changes in Mrp1-4 and ATP-binding cassette sub-family G member 2 (Abcg2) gene expressions in livers of rats.

Age-associated differences in transporter gene expression in kidneys of male rats.

Kidney transporters are involved in the secretion and reabsorption of endogenous and exogenous molecules. Numerous factors may influence their expression and affect drug disposition, efficacy and toxicity. The present study aimed to examine the development‑ and age‑associated variations in primary renal transporters in rats, including 6 uptake transporters: Organic anion transporter (OAT) 1 and 3, organic cation transporter (OCT) 1, 2 and 3 and organic anion‑transporting polypeptide (OATP) 4C1, and 6 efflux transporters: Multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance‑associated protein (MRP) 2 and 4, and multidrug and toxin extrusion protein (MATE) 1 and 2‑K.

Mercury sulfides are much less nephrotoxic than mercury chloride and methylmercury in mice.

Mercury sulfides (α-HgS, β-HgS) are frequently included in traditional medicines. Mercury is known for nephrotoxicity, their safety is of concern. To address this question, mice were orally administrated with Zuotai (54% β-HgS, 30mg/kg), α-HgS (HgS, 30mg/kg), HgCl (33.

Characterizing novel metabolic pathways of melatonin receptor agonist agomelatine using metabolomic approaches.

Agomelatine (AGM), an analog of melatonin, is a potential agonist at melatonin receptors 1/2 and a selective antagonist at 5-hydroxytryptamine 2C receptors. AGM is widely used for the treatment of major depressive episodes in adults. However, multiple adverse effects associated with AGM have been reported in clinical practice.

The Tibetan medicine Zuotai influences clock gene expression in the liver of mice.

Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions.

Liver expression of Nrf2-related genes in different liver diseases.

Background: The KEAP1-Nrf2 antioxidant signaling pathway is important in protecting liver from various insults. However, little is known about the expression of Nrf2-related genes in human liver in different diseases.

Methods: This study utilized normal donor liver tissues (n=35), samples from patients with hepatocellular carcinoma (HCC, n=24), HBV-related cirrhosis (n=27), alcoholic cirrhosis (n=5) and end-stage liver disease (n=13).

Icariin is a PPARα activator inducing lipid metabolic gene expression in mice.

Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg) for five days.

[Distinct effect of Wansheng Huafeng Dan containing ardisia crenata on renal transporters, mercury accumulation and Kim-1 expression from mercuric chloride].

To study the effect of Wansheng Huafeng Dan (WSHFD) and mercuric chloride on renal mercury (Hg) extraction transporters (Oat1, Oct2), renal mercury excretion transporters (Mrp4, Mate2K), renal mercury accumulation and kidney injury molecule-1 (Kim-1). The ancient prescription of WSHFD containing 10-fold Hg caused much lower renal mercury accumulation and renal toxicity than HgCl2 in rats, with less effect on renal transporters than HgCl2. The above indicators had no significant difference in WSHFDO, WSHFD2 and WSHFD3 groups, indicating no effect of WSHFD with reduced or no cinnabar.

Protection against phalloidin-induced liver injury by oleanolic acid involves Nrf2 activation and suppression of Oatp1b2.

This study utilized pharmacological activation of Nrf2 with oleanolic acid (OA, 22.5mg/kg, sc for 4 days) and the genetic alteration of Nrf2 (Nrf2-null, wild-type, and Keap1-HKO mice) to examine the role of Nrf2 in protection against phalloidin hepatotoxicity. Mice were given phalloidin (1.

Age- and sex-related differences of organic anion-transporting polypeptide gene expression in livers of rats.

Organic anion-transporting polypeptides (Oatps) play important roles in transporting endogenous substances and xenobiotics into the liver and are implicated in drug-drug interactions. Many factors could influence their expression and result in alterations in drug disposition, efficacy and toxicity. This study was aimed to examine the development-, aging-, and sex-dependent Oatps expression in livers of rats.

Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures.

Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis.

Expression of P450 and nuclear receptors in normal and end-stage Chinese livers.

Aim: To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers.

Methods: The end-stage liver disease samples [n = 93, including hepatocellular carcinoma (HCC), peri-HCC tissue, hepatitis B virus cirrhosis, alcoholic cirrhosis, and severe cirrhosis] and trimmed normal Chinese donor livers (n = 35) from The Institute of Organ Transplantation in Beijing, China. Total RNA was extracted, purified, and subjected to real-time RT-PCR analysis.