Expression profiling of selected genes of toxication and detoxication pathways in peripheral blood lymphocytes as a biomarker for predicting toxicity of environmental chemicals

Sharma, Amit; Kumar, Saurabh; Yadav, Sanjay; Jain, Swatantra Kumar; Parmar, Devendra

doi:10.1016/j.ijheh.2012.11.002

Cited by 13 publications

(11 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Induction of HMOX1 and NQO1 via Nrf2 induction has been explored in the past after treatment with sulphoraphone and butylated hydroxyanisole (Nioi et al, 2003;Keum et al, 2006). Sharma et al (2013) demonstrated induction of GSTp1 and NQO1 by different P450-inducing xenobiotics, suggesting regulation of activating and detoxifying enzymes in rat liver. Researchers from Daiichi Sankyo investigated the effect of different drugs on Nrf2-regulated genes in human hepatocytes and found mainly effects for HMOX1, CES, NQO1, and UGT1A1 (Takakusa et al, 2008).…”

Section: Tablementioning

confidence: 99%

Biomarkers of Flutamide-Bioactivation and Oxidative Stress In Vitro and In Vivo

Teppner

Boess

Ernst

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

The nonsteroidal androgen-receptor antagonist flutamide is associated with hepatic injury. Oxidative stress and reactive metabolite formation are considered contributing factors to liver toxicity. Here we have used flutamide as a model drug to study the generation of reactive drug metabolites that undergo redox cycling to induce oxidative stress (OS) in vitro and in vivo. Lipid peroxidation (LPO) markers, as well as genes regulated by the redox-sensitive Nrf2 pathway, have been identified as surrogates for the characterization of OS. These markers and metabolism biomarkers for drug bioactivation have been investigated to characterize drug-induced hepatic damage. Rat hepatocytes and in vivo studies showed that several LPO markers, namely the isoprostanes 15R-PD 2 , dihydro keto PE 2 , and iPF 2a -VI, as well as hydroxynonenal mercapturic acid metabolites, had increased significantly by 24 hours after flutamide treatment from 4.9 to 15.3-fold in hepatocytes and from 2.6 to 31.0-fold in rat plasma. Induction of mRNA expression levels for Nrf2-regulated genes was evident as well, with heme oxygenase 1, glutathione-S-transferase p1 and NAD(P)H dehydrogenase showing a 3.6-, 4.1-, and 1.9-fold increase in hepatocytes and 5.6-, 7.5-, and 94.1-fold in rat liver. All effects were observed at drug concentrations that did not show overt liver toxicity. Addition of an in situ hydrogen peroxide-generating system to in vitro experiments demonstrated the formation of a reactive di-imine intermediate as the responsible metabolic pathway for the generation of OS. The dataset suggests that hepatic oxidative stress conditions can be mediated via metabolic activation and can be monitored with suitable biomarkers preceding the terminal damage.

show abstract

Section: Tablementioning

confidence: 99%

Biomarkers of Flutamide-Bioactivation and Oxidative Stress In Vitro and In Vivo

Teppner

Boess

Ernst

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

show abstract

“…The most prominent phase I enzymes are cytochrome P450s (also known as CYPs) that detoxify or activate xenobiotic compounds [1]. The phase I enzymes are also known to be responsible for the metabolism of compounds present in CS, such as nicotine, benzene, polycyclic aromatic hydrocarbons (PAHs), and tobacco-specific nitrosamines (TSNAs) [1, 2]. The induction of a specific CYP has been utilized for the identification of a specific chemical exposure (e.g., induction of CYP1 family specifies the exposure to PAHs) [1, 2].…”

Section: Introductionmentioning

confidence: 99%

“…The phase I enzymes are also known to be responsible for the metabolism of compounds present in CS, such as nicotine, benzene, polycyclic aromatic hydrocarbons (PAHs), and tobacco-specific nitrosamines (TSNAs) [1, 2]. The induction of a specific CYP has been utilized for the identification of a specific chemical exposure (e.g., induction of CYP1 family specifies the exposure to PAHs) [1, 2]. The roles of various CYPs on the metabolism of CS toxicants have been discussed elsewhere in great detail [3–7].…”

Section: Introductionmentioning

confidence: 99%

Systems Approaches Evaluating the Perturbation of Xenobiotic Metabolism in Response to Cigarette Smoke Exposure in Nasal and Bronchial Tissues

Iskandar

Martin

Talikka

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue.

show abstract

“…22,23 Apaf1 was found to be downregulated in peripheral blood lymphocytes and upregulated after 3-methylcholanthrene treatment, indicating the potential of Apaf-1 serving as biomarker in apoptotic related diseases. 24 Additionally, a study reported that the inhibition of miR-155 could promote the sensitivity of lung cancer to cisplatin by regulating cellular apoptosis and DNA damage via negatively modulating the Apaf-1 pathway. 25 The results in this study demonstrated that exosomes secreted by ARPE-19 cells under OS can mediate the biological function of RPE cells through Apaf1.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from RPE cells under oxidative stress mediate inflammation and apoptosis of normal RPE cells through Apaf1/caspase‐9 axis

Fan

Hao

et al. 2020

J of Cellular Biochemistry

View full text Add to dashboard Cite

This study aims to explore the effects of exosomes, secreted by retinal pigment epithelial (RPE) cells under oxidative stress (OS), on apoptosis and inflammation of normal RPE cells. Exosomes secreted by normal RPE cells (named as exo) and rotenone (2.5 µmol/L) stimulated RPE cells (named as rot-exo) were isolated and extracted by multi-step differential centrifugation for morphology observation under a transmission electron microscopy. pcDNA3.1a, pcDNA3.1a-Apaf1, and p3xFlag-CMV-caspase-9 plasmids were constructed and transfected into ARPE-19 cells. Exosomes secreted by ARPE-19 cells were injected into the vitreous body of rats to verify the effect of Apaf1 and caspase-9 on cell apoptosis and inflammation. Co-immunoprecipitation was applied to clarify the interaction of Apaf1 with caspase-9. Exosomes secreted by rotenone stimulated ARPE-19 cells could induce cell apoptosis, oxidative injury, and inflammation in ARPE-19 cells. Exosomes secreted under OS can damage retinal functions of rats and have upregulated expression of Apaf1. Overexpression of Apaf1 in exosomes secreted under OS can cause the inhibition of cell proliferation, the increase of cell apoptosis and elicitation of inflammatory response in ARPE-19 cells. Exosomes derived from ARPE-19 cells under OS regulate Apaf1 expression to increase cell apoptosis and to induce oxidative injury and inflammatory response through a caspase-9 apoptotic pathway. K E Y W O R D S caspase-9, cell apoptosis, exosomes, reactive oxygen species, retinal pigment epithelium cells 1 | INTRODUCTION Retinal pigment epithelium (RPE) is a monolayer of cells that undertake the function and viability of photoreceptor cells. 1 RPE could provide nutrients to secure visual function and could impact the formation of the outer blood-retinal barrier which avoids nonspecific diffusion and material transportation from the choroid. 2 The degradation of RPE cells is part of the pathology involved in age-related macular degeneration (AMD) whose etiology remains to be largely determined. 3 RPE is vulnerable to oxidative stress (OS), particularly to reactive oxygen species (ROS). 4 OS is Yifeng Ke and Xiaoe Fan contributed equally to this work.

show abstract

Expression profiling of selected genes of toxication and detoxication pathways in peripheral blood lymphocytes as a biomarker for predicting toxicity of environmental chemicals

Cited by 13 publications

References 40 publications

Biomarkers of Flutamide-Bioactivation and Oxidative Stress In Vitro and In Vivo

Biomarkers of Flutamide-Bioactivation and Oxidative Stress In Vitro and In Vivo

Systems Approaches Evaluating the Perturbation of Xenobiotic Metabolism in Response to Cigarette Smoke Exposure in Nasal and Bronchial Tissues

Exosomes derived from RPE cells under oxidative stress mediate inflammation and apoptosis of normal RPE cells through Apaf1/caspase‐9 axis

Contact Info

Product

Resources

About