Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress

نویسندگان

  • Fiona E. Mutter
  • B. Kevin Park
  • Ian M. Copple
چکیده

Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre-clinical identification of chemicals and drugs with toxic liability in humans.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Homocysteine Induces Heme Oxygenase-1 Expression via Transcription Factor Nrf2 Activation in HepG2 Cells

Background: Elevated level of plasma homocysteine has been related to various diseases. Patients with hyperhomocysteinemia can develop hepatic steatosis and fibrosis. We hypothesized that oxidative stress induced by homocysteine might play an important role in pathogenesis of liver injury. Also, the cellular response designed to combat oxidative stress is primarily controlled by the transcripti...

متن کامل

Carob (Ceratonia siliqua L.) fruit hydro-alcoholic extract alleviates reproductive toxicity of lead in male mice: Evidence on sperm parameters, sex hormones, oxidative stress biomarkers and expression of Nrf2 and iNOS

Objective: Carob (Ceratonia siliqua L.) is an evergreen tree with fruits that have potent antioxidant activity. The aim of this study was to investigate alleviative effects of carob fruit hydro-alcoholic extract (CFHAE) against reproductive toxicity induced by lead (Pb) in male mice. Material and Methods: Forty-two NMRI adult male mice were randomly categorized into 7 groups (N=6). Group ...

متن کامل

Tempol relieves lung injury in a rat model of chronic intermittent hypoxia via suppression of inflammation and oxidative stress

Objective(s): Obstructive sleep apnea (OSA) is confirmed to cause lesions in multiple organs, especially in the lung tissue. Tempol is an antioxidant that has been reported to restrain inflammation and oxidative stress, with its role in OSA-induced lung injury being unclear. This study aimed to investigate the beneficial effect of tempol on chronic intermittent hypoxia (IH)-induced lung injury....

متن کامل

Determination of NRF2 and GSTM1 Expression and Biomarkers of Oxidative Stress on Smoking and Nonsmoking Sperm: A Pilot study

Background and Aims: Smoking has an influence on different semen parameters. It is regarded as a risk factor for infertility. This study aims to evaluate the effect of smoking cigarettes on the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione S-transferase Mu 1 (GSTM1) genes and biomarkers of oxidative stress in sperm. Materials and Methods: A case-control study...

متن کامل

Protective role of licochalcone B against ethanol-induced hepatotoxicity through regulation of Erk signaling

Objective(s): Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study. Materials and Methods: An in vitro model of Ethanol-induced cytotoxicity in BRL cel...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 43  شماره 

صفحات  -

تاریخ انتشار 2015