scholarly journals Differential Oxidative Stress Responses to D-Galactosamine-Lipopolysaccharide Hepatotoxicity Based on Real Time PCR Analysis of Selected Oxidant/Antioxidant and Apoptotic Gene Expressions in Rat

2011 ◽  
pp. 549-558 ◽  
Author(s):  
N. LEKIĆ ◽  
D. ČERNÝ ◽  
A. HOŘÍNEK ◽  
Z. PROVAZNÍK ◽  
J. MARTÍNEK ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Stress Responses ◽  
Caspase 3 ◽  
Histological Evaluation ◽  
Pcr Analysis ◽  
Heme Oxygenase 1 ◽  
Gene Expressions ◽  
Glutathione Peroxidase 1 ◽  
Apoptotic Pathways

Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. This study is focused on addressing the mutual relationship and early signals of these mechanisms in the D-galactosamine and lipopolysaccharide (D-GalN/LPS) hepatotoxicity model, with the help of standard liver function and biochemistry tests, histology, and measurement of gene expression by RT-PCR. Intraperitoneal injection of 400 mg/kg D-GalN and 50 μg/kg LPS was able to induce hepatotoxicity in rats, as evidenced by significant increases in liver enzymes (ALT, AST) and raised bilirubin levels in plasma. Heme oxygenase-1 and nitric oxide synthase-2 gene expressions were significantly increased, along with levels of their products, bilirubin and nitrite. The gene expression of glutathione peroxidase 1 remained unchanged, whereas a decrease in superoxide dismutase 1 gene expression was noted. Furthermore, the significant increase in the gene expression of apoptotic genes Bid, Bax and caspase-3 indicate early activation of apoptotic pathways, which was confirmed by histological evaluation. In contrast, the measured caspase-3 activity remained unchanged. Overall, the results have revealed differential oxidative stress and apoptotic responses, which deserves further investigations in this hepatotoxicity model.

scholarly journals Does lack ofglutathione peroxidase 1gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?

2017 ◽  
Vol 313 (1) ◽  
pp. L115-L125 ◽  
Author(s):  
Sheena Bouch ◽  
Megan O’Reilly ◽  
Judy B. de Haan ◽  
Richard Harding ◽  
Foula Sozo
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lung Injury ◽  
Lung Tissue ◽  
Immune Cells ◽  
Lavage Fluid ◽  
Supplemental Oxygen ◽  
Heme Oxygenase 1 ◽  
Long Term Effects ◽  
Glutathione Peroxidase 1

Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing glutathione peroxidase 1 ( GPx1) gene expression increases the injurious effects of hyperoxia (Hyp). GPx1+/+and GPx1−/−C57Bl/6J mice were exposed to 21% O2(Air) or 40% O2(Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and GPx1-4 and catalase gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of GPx1 expression and further decreased by hyperoxia. GPx1 expression was increased in GPx1+/+Hyp mice and decreased in both GPx1−/−groups. On P56d, heme oxygenase-1 was increased by hyperoxia when GPx1 was absent. There were significantly more immune cells from Hyp groups than from the GPx1+/+Air group and a greater proportion of lymphocytes in GPx1−/−Hyp mice. GPx1 expression was significantly decreased in GPx1−/−mice; GPx2-4 and catalase expression was increased in GPx1−/−Hyp mice compared with other groups. Tissue fraction was decreased in GPx1−/−Air mice; bronchiolar smooth muscle was decreased in GPx1−/−mice. GPx1 does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of GPx2-4 and catalase in GPx1−/−Hyp mice suggests gene redundancy within the model.

scholarly journals Effect of methylsulfonylmethane on oxidative stress and CYP3A93 expression in fetal horse liver cells

2021 ◽  
Vol 34 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Kyoung Hwan Kim ◽  
Jeong-Woong Park ◽  
Young Mok Yang ◽  
Ki-Duk Song ◽  
Byung-wook Cho
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cytochrome P450 ◽  
Stress Responses ◽  
Expression Profiles ◽  
Normal Liver ◽  
Liver Cells ◽  
Heme Oxygenase 1 ◽  
Genetic Characteristics ◽  
Horse Liver

Objective: Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (<i>CYP3A</i>) gene expression in fetal horse hepatocytes.Methods: The expression of hepatocyte markers and <i>CYP3A</i> family genes (<i>CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96</i>, and <i>CYP3A97</i>) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of <i>CYP3A</i> were investigated in H<sub>2</sub>O<sub>2</sub>-induced oxidative stress in the presence and absence of MSM.Results: FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and <i>CYP3A</i> genes, except that of <i>CYP3A93</i>, were different. The expression of <i>CYP3A93</i> specifically increased after the addition of H<sub>2</sub>O<sub>2</sub> to the culture medium. MSM treatment reduced oxidative stress as well as the expression of <i>CYP3A93</i> and heme oxygenase 1, an oxidative marker in FHLCs.Conclusion: MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering <i>CYP3A93</i> expression and related signaling pathways.

Chemoprotective Effects of Propolis on Aflatoxin B1-Induced Hepatotoxicity in Rats: Oxidative Damage and Hepatotoxicity by Modulating TP53, Oxidative Stress

2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Oxidative Damage ◽  
Aflatoxin B1 ◽  
Tp53 Gene ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Gene Expressions ◽  
Cat Gene ◽  
Gst Activity

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.

scholarly journals Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

2021 ◽  
Vol 35 ◽  
pp. 205873842110314
Author(s):  
Fei Zeng ◽  
Jierong Luo ◽  
Hong Han ◽  
Wenjie Xie ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Caspase 3 ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Liver Protein ◽  
Lipid Peroxidation Product ◽  
Protein Expressions

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

scholarly journals The Arabidopsis mediator complex subunit 8 regulates oxidative stress responses

2021 ◽  
Author(s):  
Huaming He ◽  
Jordi Denecker ◽  
Katrien Van Der Kelen ◽  
Patrick Willems ◽  
Robin Pottie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Salicylic Acid ◽  
Jasmonic Acid ◽  
Stress Responses ◽  
Negative Regulator ◽  
Mediator Complex ◽  
Defense Gene Expression ◽  
A Genome ◽  
Oxidative Stress Responses

Abstract Signaling events triggered by hydrogen peroxide (H2O2) regulate plant growth and defense by orchestrating a genome-wide transcriptional reprogramming. However, the specific mechanisms that govern H2O2-dependent gene expression are still poorly understood. Here, we identify the Arabidopsis Mediator complex subunit MED8 as a regulator of H2O2 responses. The introduction of the med8 mutation in a constitutive oxidative stress genetic background (catalase-deficient, cat2) was associated with enhanced activation of the salicylic acid pathway and accelerated cell death. Interestingly, med8 seedlings were more tolerant to oxidative stress generated by the herbicide methyl viologen (MV) and exhibited transcriptional hyperactivation of defense signaling, in particular salicylic acid- and jasmonic acid-related pathways. The med8-triggered tolerance to MV was manipulated by the introduction of secondary mutations in salicylic acid and jasmonic acid pathways. In addition, analysis of the Mediator interactome revealed interactions with components involved in mRNA processing and microRNA biogenesis, hence expanding the role of Mediator beyond transcription. Notably, MED8 interacted with the transcriptional regulator NEGATIVE ON TATA-LESS, NOT2, to control the expression of H2O2-inducible genes and stress responses. Our work establishes MED8 as a component regulating oxidative stress responses and demonstrates that it acts as a negative regulator of H2O2-driven activation of defense gene expression.

scholarly journals Effects of glutamine supplementation on oxidative stress-related gene expression and antioxidant properties in rats with streptozotocin-induced type 2 diabetes

2011 ◽  
Vol 107 (8) ◽  
pp. 1112-1118 ◽  
Author(s):  
Pei-Hsuan Tsai ◽  
Jun-Jen Liu ◽  
Chui-Li Yeh ◽  
Wan-Chun Chiu ◽  
Sung-Ling Yeh
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Amino Acid ◽  
Oxidative Damage ◽  
Antioxidant Capacity ◽  
Enzyme Activities ◽  
Antioxidant Enzyme Activities ◽  
Related Gene ◽  
Gene Expressions ◽  
Oxidative Stress Related Gene

There are close links among hyperglycaemia, oxidative stress and diabetic complications. Glutamine (GLN) is an amino acid with immunomodulatory properties. The present study investigated the effect of dietary GLN on oxidative stress-relative gene expressions and tissue oxidative damage in diabetes. There were one normal control (NC) and two diabetic groups in the present study. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin (STZ). Rats in the NC group were fed a regular chow diet. In the two diabetic groups, one group (diabetes mellitus, DM) was fed a common semi-purified diet while the other group received a diet in which part of the casein was replaced by GLN (DM-GLN). GLN provided 25 % of total amino acid N. The experimental groups were fed the respective diets for 8 weeks, and then the rats were killed for further analysis. The results showed that blood thioredoxin-interacting protein (Txnip) mRNA expression in the diabetic groups was higher than that in the NC group. Compared with the DM group, the DM-GLN group had lower glutamine fructose-6-phosphate transaminase 1, a receptor of advanced glycation end products, and Txnip gene expressions in blood mononuclear cells. The total antioxidant capacity was lower and antioxidant enzyme activities were altered by the diabetic condition. GLN supplementation increased antioxidant capacity and normalised antioxidant enzyme activities. Also, the renal nitrotyrosine level and Txnip mRNA expression were lower when GLN was administered. These results suggest that dietary GLN supplementation decreases oxidative stress-related gene expression, increases the antioxidant potential and may consequently attenuate renal oxidative damage in rats with STZ-induced diabetes.

Dexrazoxane does not protect against doxorubicin-induced damage in young rats

2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Weight Gain ◽  
Heme Oxygenase ◽  
Caspase 3 ◽  
Exercise Program ◽  
Female Rats ◽  
Male Rats ◽  
Heme Oxygenase 1 ◽  
Cardiac Damage

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.

Abstract 253: Di-n-butyl Phthalate: An Indoor Pollutant Induces Murine Macrophages Oxidative Stress and Inflammation, a Potential Atheropathogenesis Modulator

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Zahra Mazhar ◽  
Dhuha Alsayrafi ◽  
Tong Wu ◽  
Mahdi Garelnabi
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Tnf Alpha ◽  
Gene Expressions ◽  
Compensatory Response ◽  
Murine Macrophages ◽  
Atherosclerosis Progression ◽  
Indoor Pollutant ◽  
Human Cardiovascular System ◽  
Butyl Phthalate

Di-n-butyl phthalate (DBP) is used in air fresheners. It is a colorless oily compound which also used for manufacturing bendable plastics. DBP can cause low acute or chronic toxicity; however, the effect of DBP on humans in the form of air fresheners is not well studied. The effect of DBP on the human cardiovascular system has not been studied. Macrophages are involved in atherosclerosis progression and development; murine macrophages (RAW 264.7) were used for this study. The macrophages were treated with 10uM, 20uM and 50uM DBP for 6 hours, 12 hours and 24 hours. Genes involved in inflammation and antioxidant activity like TNF-a, MCP-1, VCAM-1, NF-kB, PON1, SOCS were analyzed after treatment. macrophages showed statistically significant increases in TNF-alpha expression (p≤ 0.05) after 24 hour treatment with DBP. The expression of NF-kB showed a significant increase in response to DBP treatment (p≤ 0.05) at 24 hours. MCP-1 and VCAM-1 gene expressions were also upregulated after exposure to DBP. Interestingly, catalase gene expression was upregulated in all treatments after 24 hours of exposure however PON-1 gene expression showed differential upregulation responses. Our data clearly suggest that DBP induces inflammation in macrophages. PON1 and catalase upregulated gene expression indicative of a compensatory response to oxidative stress associated with the treatment. Oxidative stress and inflammation mediated macrophages responses strongly linked to atherosclerosis pathogenesis.

scholarly journals Strigolactone GR24 upregulates Nrf2 target genes and may protect against oxidative stress in skeletal muscle

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1459
Author(s):  
Shalem Raju Modi ◽  
Tarja Kokkola
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factor ◽  
Stress Responses ◽  
Mycorrhizal Fungi ◽  
Target Genes ◽  
Redox Homeostasis ◽  
Antioxidant Defences ◽  
Microarray Gene Expression

GR24 is a synthetic strigolactone analog, demonstrated to regulate the development of plants and arbuscular mycorrhizal fungi. GR24 possesses anti-cancer and anti-apoptotic properties, enhances insulin sensitivity and mitochondrial biogenesis in skeletal myotubes, inhibits adipogenesis, decreases inflammation in adipocytes and macrophages and downregulates the expression of hepatic gluconeogenic enzymes. Transcription factor Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) is a master regulator of antioxidant response, regulating a multitude of genes involved in cellular stress responses and anti-inflammatory pathways, thus maintaining cellular redox homeostasis. Nrf2 activation reduces the deleterious effects of mitochondrial toxins and has multiple roles in promoting mitochondrial function and dynamics. We studied the role of GR24 on gene expression in rat L6 skeletal muscle cells which were differentiated into myotubes. The myotubes were treated with GR24 and analyzed by microarray gene expression profiling. GR24 upregulated the cytoprotective transcription factor Nrf2 and its target genes, activating antioxidant defences, suggesting that GR24 may protect skeletal muscle from the toxic effects of oxidative stress.

scholarly journals Transcriptome changes in undifferentiated Caco-2 cells exposed to food-grade titanium dioxide (E171): contribution of the nano- and micro- sized particles

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Héloïse Proquin ◽  
Marloes C. M. Jonkhout ◽  
Marlon J. Jetten ◽  
Henk van Loveren ◽  
Theo M. de Kok ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Titanium Dioxide ◽  
Immune System ◽  
Stress Responses ◽  
Inflammatory Responses ◽  
Relative Contribution ◽  
Immune System Activation ◽  
Favourable Environment

AbstractThe food additive titanium dioxide (TiO2), or E171, is a white food colorant. Recent studies showed after E171 ingestion a significantly increased number of colorectal tumours in a colorectal cancer mouse model as well as inflammatory responses and dysregulation of the immune system in the intestine of rats. In the mouse colon, E171 induced gene expression changes related to oxidative stress, impairment of the immune system, activation of signalling and cancer-related processes. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed that E171, NPs and MPs induced oxidative stress responses, DNA damage and micronuclei formation. This study aimed to investigate the relative contribution of the NPs and MPs to effects of E171 at the transcriptome level in undifferentiated Caco-2 cells by genome wide microarray analysis. The results showed that E171, NPs, and MPs induce gene expression changes related to signalling, inflammation, immune system, transport and cancer. At the pathway level, metabolism of proteins with the insulin processing pathway and haemostasis were specific to E171 exposure. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for colon cancer development.

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