Oltipraz

The role of hepatic nuclear factor 1α (HNF-1α) and its response element in the expression of glutathione S-transferase A1 (GSTA1) was investigated in hepatocytes cells injury induced by acetaminophen (APAP). Treatment of hepatocytes with C2-ceramide exacerbated cells injury with GSTA1 mRNA level reducing. Contrastingly, administration of oltipraz alleviated cells damage with GSTA1 mRNA level elevating relative to hepatotoxicity induced by APAP. Western blot analysis showed that C2-ceramide decreased the translocation of HNF-1α and expression of GSTA1 protein, while oltipraz increased nuclear HNF-1α level and transactivation of GSTA1...

OBJECTIVE: To evaluate the effect of oltipraz (OPZ) on isoproterenol-induced heart failure (HF) and heart function. We also explore the underlying molecular mechanism of OPZ. MATERIALS AND METHODS: The rats were randomly divided into four groups, including normal control group, isoproterenol (ISO) group, ISO +100 mg/kg OPZ group, and OPZ group. Hemodynamic parameters, such as left-ventricular systolic pressure, were statistically analyzed. Besides, plasma levels of brain natriuretic peptide (BNP), pro-inflammatory cytokines and antioxidant markers were assessed by using enzyme-linked immunosorbent assay (ELISA)...

BACKGROUND: Pterygium is a condition characterized by epithelial overgrowth of the cornea, inflammatory cell infiltration and an abnormal extracellular matrix accumulation. Chronic UV exposure is considered as a pathogenic factor of this disease. Proteasome is an intracellular multi-subunit protease complex that degrades intracellular proteins. Among proteasome subunits the β5 (PSMB5), bearing chymotrypsin-like activity. It is considered as the main proteasome subunit and its expression is mediated by Nrf2-ARE pathway in many cell types...

Rapamycin (sirolimus) is employed as an immunosuppressant following liver transplant, to inhibit the re-growth of cancer cells following liver resection for hepatocellular carcinoma (HCC), and for the treatment of advanced HCC. Rapamycin also induces the expression of antioxidant enzymes in the liver, suggesting that pretreatment with the drug could provide a potential strategy to reduce ischemia reperfusion injury following liver surgery. The aim of this study was to further investigate the actions of rapamycin in inducing expression of the antioxidant enzymes heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prx-1) in normal liver and in tumorigenic liver cells...

Central presbycusis is the most common sensory disorder in the elderly population, however, the underlying molecular mechanism remains unclear. NF‑E2‑related factor 2 (Nrf2) is a key transcription factor in the cellular response to oxidative stress, however, the role of Nrf2 in central presbycusis remains to be elucidated. The aim of the present study was to investigate the pathogenesis of central presbycusis using a mimetic aging model induced by D‑galactose (D‑gal) in vivo and in vitro...

In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment...

Chronic obstructive pulmonary disease (COPD) is among the most important causes of death. Signaling systems that are relevant for tissue repair and detoxification of reactive oxygen species or xenobiotics are thought to be impaired in lungs of patients suffering from this disease. Here, we developed a simple cigarette smoke induced Drosophila model of COPD based on chronic cigarette smoke exposure that recapitulates major pathological hallmarks of the disease and thus can be used to investigate new therapeutic strategies...

INTRODUCTION: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. MATERIALS AND METHODS: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration...

BACKGROUND: Vascular endothelial cells (EC) are constantly exposed to endo- and exogenous compounds, which may disturb EC function. One of the protecting mechanisms against chemicals consists of drug metabolizing enzymes and transporter proteins regulated by nuclear receptors and transcription factors. Therefore, the aim of the current study was to assess the regulation of nuclear receptors and their coordinated genes in Human Umbilical Vein Endothelial Cells (HUVEC). METHODS: HUVEC were exposed to TCDD (10nM), oltipraz (100μM) and simvastatin (1μM) for 24h...

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by an accelerated aging phenotype that typically leads to death via stroke or myocardial infarction at approximately 14.6 years of age. Most cases of HGPS have been linked to the extensive use of a cryptic splice donor site located in the LMNA gene due to a de novo mutation, generating a truncated and toxic protein known as progerin. Progerin accumulation in the nuclear membrane and within the nucleus distorts the nuclear architecture and negatively effects nuclear processes including DNA replication and repair, leading to accelerated cellular aging and premature senescence...

Although metformin (MET) may be useful for the treatment of psoriasis, the mechanisms underlying its method of action have yet to be fully elucidated. Here, the relationship between MET function and reactive oxygen species (ROS) levels and the underlying mechanism were explored in human immortalized keratinocyte cell line (HaCaT). HaCaT cells were incubated with MET at 0, 10, 20, 40, and 60 mM for 24 h. The cell viability was evaluated by the CCK-8 assay. The cell apoptosis rate and intracellular ROS levels were examined using flow cytometry...

We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined rat immortalized RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2), or angiotensin 1-7 (Ang 1-7) receptor (MasR) gene promoters...

Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2)-like 2 (Nrf2) is a transcription factor involved in kidney protectant effects. The purpose of this study was to determine whether the Nrf2 activators oltipraz, sulforaphane, and oleanolic acid could protect human kidney cells against cisplatin-induced injury and to compare the protective effects between three Nrf2 activators. Human proximal tubule cells (hPTC) and human embryonic kidney 293 cells (HEK293) were exposed to cisplatin doses in the absence and presence of Nrf2 activators...

A pyrrolopyrazine-thione derived from oltipraz, a compound that has been investigated as a chemopreventive agent, affords radicals in the presence of thiols and oxygen via a redox cycle, an attribute that suggests its suitability as an initiator for oxygen-mediated polymerization. Here, we explore the utilization of this pyrrolopyrazine-thione, generated in situ from a precursor, as an initiator for the radical-mediated thiol-ene polymerization. While the pyrrolopyrazine-thione was shown to be capable of generating radicals in the presence of atmospheric oxygen and thiol groups, the reaction extents achievable were lower than desired owing to the presence of unwanted side reactions that would quench radical production and, subsequently, suppress polymerization...

BACKGROUND: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. AIM: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a multicentre, double-blind, placebo-controlled, phase II study...

The exposure of cells to low doses of stress induces adaptive survival responses that protect cells against subsequent exposure to toxic stress. The ability of cells to resist subsequent toxic stress following exposure to low dose heat stress at 40°C is known as mild thermotolerance. Mild thermotolerance involves increased expression of heat shock proteins and antioxidants, but the initiating factors in this response are not understood. This study aims to understand the role of the Nrf2 antioxidant pathway in acquisition of mild thermotolerance at 40°C, and secondly, whether the Nrf2 pathway could be involved in the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis...

A new series of 4,5-diaryl-3H-1,2-dithiole-3-thiones and related compounds were designed and synthesised as combretastatin A-4/oltipraz hybrids. We evaluated the antiproliferative activities, inhibition of tubulin polymerization, and cell-cycle effects of these compounds. Several compounds in this series, such as 4d and 5c, displayed significant activity against SGC-7901, KB and HT-1080 cell lines, as determined using MTT assays. The most active compound, 4d, markedly inhibited tubulin polymerization, with an IC50 value of 4...

OBJECTIVE: To determine the effects of topical administration of 20% oltipraz solution on histomorphometrical and stereological aspects of skin tissue in full thickness skin wounds in laboratory rats. METHODS: Thirty-six male Wistar portion rats (220±20 g) were randomly divided into three groups (n=12). On the first day of experimentation, a 1-cm2 circular wound was made on the posterior surface of neck in all rats by removing a full thickness skin piece immediately after induction of anesthesia with ether inhalation...

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor which is strongly associated with tumor survival, progression, and therapeutic resistance. Accordingly, it has been suggested that the inhibition of the HIF-1 pathway can suppress tumor, and it has become an important therapeutic target. In present study, oltipraz, its metabolite M2, and their derivatives were synthesized and evaluated as HIF-1α inhibitors. Among the synthesized, benzyl-substituted pyrrolo[1,2-a]pyrazine 2g most potently inhibited HIF-1α protein accumulation (81% at 10μM) and VEGF, GLUT-1 transcription (77% and 92% at 10μM, respectively)...

Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters...