Quercetin protects the buffalo rat liver (BRL-3A) cells from aflatoxin B1-induced cytotoxicity via activation of Nrf2-ARE pathway

2020 ◽  
Vol 13 (2) ◽  
pp. 299-312
Author(s):  
X. Wang ◽  
L. Li ◽  
G. Zhang
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Rat Liver ◽  
Chromatin Condensation ◽  
Dna Integrity ◽  
Related Factor ◽  
Mitochondria Membrane Potential ◽  
Lactate Dehydrogenase Release ◽  
Phosphorylated Akt ◽  
Pre Treatment

Aflatoxin B1 (AFB1) is the most toxic mycotoxin widely presented in agricultural products, and the protective effect of quercetin (QUE), a natural antioxidant, against AFB1-induced cytotoxicity to the buffalo rat liver (BRL-3A) cells was investigated. With an IC50 of 23 μM, AFB1 induced a significant oxidative stress to BRL-3A cells evidenced by a dose-dependent reduction of mitochondria membrane potential (MMP), ATP content, and activities of endogenous antioxidant enzymes along with increased levels of reactive oxygen species (ROS) and lipid peroxidation biomarker of malondialdehyde (MDA). The activity of CYP1A2, the key enzyme to convert AFB1 to reactive AFB1 exo-8,9- epoxide, was also increased, which, probably in together with ROS, led to cell apoptosis with DNA fragmentation, chromatin condensation and increased lactate dehydrogenase release. After the BRL cells were pre-treated by low level QUE (2.5 and/or 5 μM) for 24 h and then exposed to AFB1, the activities of antioxidant enzymes including haeme oxygenase-1, glutathione S-transferase, superoxide dismutase, and the ratio of reduced to oxidised glutathione were significantly increased whereas the levels of intracellular ROS and MDA were reduced. The QUE pre-treatment also increased the levels of MMP, ATP and DNA integrity, and reduced the expression of apoptosis related genes of Bax and Caspase-3. The Western blotting study revealed increased content of phosphorylated Akt and nuclear NF-E2-related factor 2 (Nrf2), indicating an activation of Nrf2-ARE pathway in counteracting oxidative stress and cytotoxicity of AFB1. Thus, the QUE pre-treatment enhanced the anti-stress capacity of the cells through the activation of the Nrf2-ARE pathway, and QUE-based measures could be developed to ameliorate the toxicity caused by AFB1.

Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury

2019 ◽  
Vol 97 (4) ◽  
pp. 287-292 ◽  
Author(s):  
Branislav Kura ◽  
Ashim K. Bagchi ◽  
Pawan K. Singal ◽  
Miroslav Barancik ◽  
Tyler W. LeBaron ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Hydrogen ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Functions ◽  
Artificial System ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Pre Treatment

Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of•OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidants and reduction of apoptosis, as well as inflammation.

scholarly journals N-Acetylcysteine Attenuates Monocrotophos-induced Toxicity by Mitigating Oxidative Stress and Structural Changes in Rat Liver

2021 ◽  
Author(s):  
Jagjeet Singh ◽  
Annu Phogat ◽  
Chandra Prakash ◽  
Vijay Kumar ◽  
Vinay Malik
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Rat Liver ◽  
Protein Oxidation ◽  
Liver Tissue ◽  
Structural Changes ◽  
Microscopic Analysis ◽  
Stress Generation ◽  
Electron Microscopic ◽  
Pre Treatment

Abstract The present study evaluated the effect of N-acetylcysteine (NAC) against sub chronic monocrotophos (MCP) exposure induced oxidative stress in rat liver. Albino wistar rats were divided into control, NAC treated, MCP and MCP treated groups. An oral dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) was administered for 28 days. We observed high oxidative stress generation on MCP exposure in liver tissue as evident by significant increase in lipid peroxidation, protein oxidation and decreased glutathione content followed by altered activities of superoxide dismutase, catalase and acetylcholinesterase. Sub chronic MCP exposure caused an array of cellular and structural alternations in lipids and proteins of liver tissue as depicted by the FTIR, histopathological and electron microscopic analysis. N-acetylcysteine attenuated the loss of glutathione and prevented lipid peroxidation and protein oxidation. Pre-treatment of NAC also restored histological and ultra space structural alternations. So NAC protects oxidative stress and tissue damage induced by sub chronic MCP exposure in rat liver; suggesting the therapeutic and antioxidant potential of NAC.

The Effects of Moderate, Strenuous, and Overtraining on Oxidative Stress Markers and DNA Repair in Rat Liver

2005 ◽  
Vol 30 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Helga Ogonovszky ◽  
Maria Sasvári ◽  
Agoston Dosek ◽  
István Berkes ◽  
Takao Kaneko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Rat Liver ◽  
Nuclear Dna ◽  
Activity Levels ◽  
Carbonyl Derivative ◽  
Stress Markers ◽  
Cell Extracts

Physical exercise above a certain load has been suggested as being a cause of oxidative stress. We have tested whether training with moderate (MT), strenuous (ST), or over (OT) load can cause alterations in the activities of antioxidant enzymes, lipid peroxidation, protein oxidation, DNA damage, or activity of 8-oxoG-DNA glycosylase (OGG1) in rat liver. The levels of corticosterone decreased in all exercising groups but the differences were not significant. Adrenocorticotrophin hormone (ACTH) levels decreased, not significantly, in MT and OT compared to C. Activity levels of antioxidant enzymes did not change significantly in the liver. The levels of reactive carbonyl derivative (RCD) content decreased in the liver of exercising animals, and the differences reached significance between control and moderately trained groups. The changes in the levels of lipid peroxidation (LIPOX) were not significant, but were lower in the exercised groups. The 8-hydroxydeoxyguanosine (8-OHdG) levels increased in the OT group, and the activity of OGG1 measured from crude cell extracts tended to increase in MT and ST. The findings of this study imply that overtraining induces oxidative damage to nuclear DNA, but not to liver lipids and proteins. Key words: exercise, oxidative damage, adaptation, OGG1

Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver

2005 ◽  
Vol 156 (2-3) ◽  
pp. 101-111 ◽  
Author(s):  
Anil K Bansal ◽  
Manju Bansal ◽  
Giridhar Soni ◽  
Deepak Bhatnagar
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Rat Liver ◽  
Protective Role ◽  
Pre Treatment

Abstract 067: Downregulation Of Vascular Factor-erythroid 2-related Factor-2 And Associated Antioxidant Enzymes In Hypertension

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Rheure A Lopes ◽  
Karla B Neves ◽  
Augusto Montezano ◽  
Rita Tostes ◽  
Rhian Touyz
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Mrna Expression ◽  
Vascular Dysfunction ◽  
Ros Generation ◽  
Related Factor ◽  
Mrna Levels ◽  
Ang Ii ◽  
Peroxiredoxin 1 ◽  
Anti Oxidant

Oxidative stress plays an important role in vascular dysfunction in hypertension. While mechanisms regulating vascular pro-oxidants are emerging, there is a paucity of information on anti-oxidant systems. Factor-erythroid 2-related factor-2 (Nrf2) is a master regulator of antioxidants and its role in hypertension remains elusive. We assessed vascular Nrf2 in hypertension by studying mesenteric vessels and VSMCs from WKY and SHRSP rats. Cells were stimulated with Ang II (10-7M) in the absence/presence of Nrf2 activators (bardoxolone or L-sulforaphane). ROS generation was assessed by chemiluminescence and amplex red. mRNA expression of anti-oxidant enzymes was assessed by qPCR. Nrf2 activity was analyzed by ELISA. Nrf2 activity was decreased in arteries (18%) and VSMCs (48%) in SHRSP (p<0.05 vs WKY). mRNA levels of antioxidant enzymes were reduced in SHRSP (SOD 1 (64%), catalase (60%), peroxiredoxin 1 (75%) and glutathione peroxidase (54%) Ang II increased Nrf2 activity in VSMCs from WKY (197%, 4h) and SHRSP (44%, 4h) (p<0.05, vs. vehicle). This was associated with increased antioxidant mRNA expression in WKY rats (SOD1-32%, catalase-42%, thioredoxin-71%, peroxiredoxin 1-90%, quinone oxidoreductase-84%; p<0.05 vs. vehicle) but not in SHRSP. ROS production and glucose-6-phosphate dehydrogenase (source of NADPH) mRNA levels were increased in SHRSP. Ang II-induced ROS generation in VSMCs from WKY and SHRSP was blocked by Nrf2 activators. Vascular function assessment, by wire myography, demonstrated that increased contractility (Emax Phe: WKY 113.4±5,67 vs. SHRSP 159.0±8.29) and decreased endothelial-dependent relaxation (Emax ACh: WKY 88.7±3.13 vs. SHRSP 74.7±3.25, p<0.05) in SHRSP were corrected by bardoxolone and L-sulforaphane. In conclusion, vascular dysfunction in SHRSP is associated with oxidative stress, decreased Nrf2 activity and reduced Nrf2-regulated antioxidant enzymes. A similar molecular phenotype was observed in Ang II-stimulated VSMCs. Nrf-2 agonists ameliorated vascular dysfunction in SHRSP. Our findings suggest that Nrf-2 downregulation may contribute to redox-sensitive vascular dysfunction and could be a therapeutic target in hypertension. Financial Support: ScWB.

Protective Role of Natural Products in Cisplatin-Induced Nephrotoxicity

2019 ◽  
Vol 19 (14) ◽  
pp. 1134-1143 ◽  
Author(s):  
Nurul Raudzah Adib Ridzuan ◽  
Norhashima Abd Rashid ◽  
Faizah Othman ◽  
Siti Balkis Budin ◽  
Farida Hussan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Natural Products ◽  
Antioxidant Enzymes ◽  
Antineoplastic Agent ◽  
Protective Role ◽  
Vitamin Supplementation ◽  
Anti Inflammatory ◽  
Pre Treatment ◽  
Higher Doses

Cisplatin is a widely used antineoplastic agent for the treatment of metastatic tumors, advanced bladder cancer and many other solid tumors. However, at higher doses, toxicities such as nephrotoxicity may appear. Cisplatin leads to DNA damage and subsequently renal cell death. Besides that, oxidative stress is also implicated as one of the main causes of nephrotoxicity. Several studies showed that numerous natural products: ginseng, curcumin, licorice, honey and pomegranate were able to reduce the oxidative stress by restoring the levels of antioxidant enzymes and also at the same time act as an anti-inflammatory agent. Furthermore, pre-treatment with vitamin supplementation, such as vitamin C, E and riboflavin markedly decreased serum urea and increased the levels of antioxidant enzymes in the kidney even after cisplatin induction in cancer patients. These natural products possess potent antioxidant and anti-inflammatory medicinal properties, and they can be safely used as a supplementary regime or combination therapy against cisplatin-induced nephrotoxicity. The present review focused on the protective role of a few natural products which is widely used in folk medicines in cisplatin-induced nephrotoxicity.

scholarly journals 6′-O-Galloylpaeoniflorin Attenuates Cerebral Ischemia Reperfusion-Induced Neuroinflammation and Oxidative Stress via PI3K/Akt/Nrf2 Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhongmei Wen ◽  
Weichen Hou ◽  
Wei Wu ◽  
Yang Zhao ◽  
Xuechao Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Phosphorylated Akt

6′-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

scholarly journals Mammary gene expression and activity of antioxidant enzymes and oxidative indicators in the blood, milk, mammary tissue and ruminal fluid of dairy cows fed flax meal

2013 ◽  
Vol 110 (10) ◽  
pp. 1743-1750 ◽  
Author(s):  
Ana Luiza Bachmann Schogor ◽  
Marie-France Palin ◽  
Geraldo Tadeu dos Santos ◽  
Chaouki Benchaar ◽  
Pierre Lacasse ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Dairy Cows ◽  
Mrna Abundance ◽  
Holstein Cows ◽  
Mammary Tissue ◽  
Related Factor ◽  
Nuclear Factor ◽  
Ruminal Fluid ◽  
And Oxidative Stress

The effects of flax meal (FM) on the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)) in the blood, mammary tissue and ruminal fluid, and oxidative stress indicators (thiobarbituric acid-reactive substances (TBARS) and 1,1-diphenyl-2-picrylhydrazyl-scavenging activity) in the milk, plasma and ruminal fluid of dairy cows were determined. The mRNA abundance of the antioxidant enzymes and oxidative stress-related genes was assessed in mammary tissue. A total of eight Holstein cows were used in a double 4 × 4 Latin square design. There were four treatments in the diet: control with no FM (CON) or 5 % FM (5FM), 10 % FM (10FM) and 15 % FM (15FM). There was an interaction between treatment and time for plasma GPx and CAT activities. Cows supplemented with FM had a linear reduction in TBARS at 2 h after feeding, and there was no treatment effect at 0, 4 and 6 h after feeding. TBARS production decreased in the milk of cows fed the 5FM and 10FM diets. There was a linear increase in nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) mRNA abundance in mammary tissue with FM supplementation. A linear trend for increased mRNA abundance of the CAT gene was observed with higher concentrations of FM. The mRNA abundance of CAT, GPx1, GPx3, SOD1, SOD2, SOD3 and nuclear factor of κ light polypeptide gene enhancer in B-cells (NFKB) genes was not affected by the treatment. These findings suggest that FM supplementation can improve the oxidative status of Holstein cows as suggested by decreased TBARS production in ruminal fluid 2 h post-feeding and increased NFE2L2/nuclear factor-E2-related factor 2 (Nrf2) mRNA abundance in mammary tissue.

Sign in / Sign up

Export Citation Format

Share Document