scholarly journals t-BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO-1 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Fang Ye ◽  
Xiaoyi Li ◽  
Lili Li ◽  
Jing Yuan ◽  
Jun Chen
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Lead Toxicity ◽  
Treated Group ◽  
Protective Effects ◽  
Sod Activity ◽  
Nissl Staining ◽  
Nrf2 Activator

The neurotoxicity of lead has been well established, and oxidative stress is strongly associated with lead-induced neurotoxicity. Nrf2 is important for protection against oxidative stress in many disease models. We applied t-BHQ, which is an Nrf2 activator, to investigate the possible role of Nrf2 in the protection against lead neurotoxicity. t-BHQ significantly attenuated the oxidative stress in developmental rats by decreasing MDA level, as well as by increasing SOD activity and GSH content, in the hippocampus and frontal cortex. Furthermore, neuronal apoptosis was detected by Nissl staining, and Bax expression was inhibited in the t-BHQ-treated group. Results showed that t-BHQ suppressed ROS production and caspase 3/7 activity but increased intracellular GSH content, in SH-SY5Y cells under lead exposure. Moreover,in vivoandin vitro, t-BHQ enhanced the nuclear translocation of Nrf2 and binding to ARE areas but did not induce Nrf2 transcription. These phenomena were confirmed using RT-PCR, EMSA, Western blot, and immunofluorescence analyses. Subsequent upregulation of the expression of HO-1, NQO1, and GCLC was observed. However, knockdown of Nrf2 or HO-1 adversely affected the protective effects of t-BHQ against lead toxicity in SH-SY5Y cells. Thus, t-BHQ can protect against lead neurotoxicity, depending on the Nrf2/HO-1 pathway.

scholarly journals Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion in Vitro and in Liver-Humanized Mice

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Raghubendra Singh Dagur ◽  
Moses New-Aaron ◽  
Murali Ganesan ◽  
Weimin Wang ◽  
Svetlana Romanova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Treated Group ◽  
Human Hepatocytes ◽  
In Vivo Studies ◽  
People Living With Hiv ◽  
Humanized Mouse Model ◽  
And Function

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.

Abstract 352: Real-time Intravital Optical Imaging Reflects the Dynamic Changes of Oxidative Stress Induced by Cigarette Smoking in Vasculatures

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ji Bak Kim ◽  
Jiheun Ryu ◽  
Joon Woo Song ◽  
Dong Joo Oh ◽  
DaeGab Gweon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoking ◽  
Optical Imaging ◽  
Real Time ◽  
Treated Group ◽  
Fluorescence Signal ◽  
Ros Production ◽  
Protective Effects ◽  
Dynamic Changes

Background: Reactive oxygen species (ROS) play a central role in cigarette smoking-induced atherogenesis. The present study aims to assess the smoking-induced acute oxidative stress within vasculatures, and evaluates whether the resveratrol, a natural polyphenol antioxidant, can counteract this ROS production, using a customized, high resolution intravital optical imaging in real-time. Methods and Results: 20-week-old male C57BL/6 mice were divided into four groups according to the preceding administration of resveratrol (R) (25mg/kg via gavage, for 7 days) and exposure to cigarette smoke (CS). To in vivo assess acute oxidative stress in blood vessels, dihydroethidium, which forms a red fluorescence (ethidium, excitation/emission: 520nm/610nm) upon reaction with ROS, was injected intraperitoneally. During CS exposure, temporal changes of fluorescence signals from the mouse cremaster muscle including vasculatures were assessed by intravital optical imaging for 15 minutes. Fluorescence signals were much more pronounced in CS exposed mice than controls (p<0.001). Resveratrol p.o. significantly reduced the CS-induced ROS signals compared to the non-treated group (fluorescence signal to noise ratio, SNR, 2.51±0.09 vs. 12.52±2.116, p=0.0002) (Figure A). Without CS exposure, fluorescence signals in targeted vasculatures were very low showing no difference between groups (SNR, 1.65±0.19 vs. 1.53±0.07, p=0.80) (Figure A). Lipid peroxidation was increased in CS group and significantly attenuated in resveratrol-treated mice (Figure B). Fluorescence microscopy and immunostainings corroborated the in vivo findings. Conclusions: The intravital optical imaging was able to in vivo estimate the dynamic changes of ROS production by CS exposure. Our data demonstrated that even a brief exposure to CS increased oxidative stress in vasculatures promptly, and the resveratrol exerts protective effects against the CS-induced acute oxidative stress.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals Caffeine Modulates Cadmium-Induced Oxidative Stress, Neuroinflammation, and Cognitive Impairments by Regulating Nrf-2/HO-1 In Vivo and In Vitro

2019 ◽  
Vol 8 (5) ◽  
pp. 680 ◽  
Author(s):  
Amjad Khan ◽  
Muhammad Ikram ◽  
Tahir Muhammad ◽  
Junsung Park ◽  
Myeong Ok Kim
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cognitive Deficits ◽  
Calcium Binding ◽  
Neuronal Loss ◽  
Treated Group ◽  
Nuclear Factor ◽  
Acute And Chronic Exposure

Cadmium (Cd), a nonbiodegradable heavy metal and one of the most neurotoxic environmental and industrial pollutants, promotes disturbances in major organs and tissues following both acute and chronic exposure. In this study, we assessed the neuroprotective potential of caffeine (30 mg/kg) against Cd (5 mg/kg)-induced oxidative stress-mediated neuroinflammation, neuronal apoptosis, and cognitive deficits in male C57BL/6N mice in vivo and in HT-22 and BV-2 cell lines in vitro. Interestingly, our findings indicate that caffeine markedly reduced reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and hemeoxygenase-1 (HO-1), which act as endogenous antioxidant regulators. Also, 8-dihydro-8-oxoguanine (8-OXO-G) expression was considerably reduced in the caffeine-treated group as compared to the Cd-treated group. Similarly, caffeine ameliorated Cd-mediated glial activation by reducing the expression of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), and other inflammatory mediators in the cortical and hippocampal regions of the mouse brain. Moreover, caffeine markedly attenuated Cd-induced neuronal loss, synaptic dysfunction, and learning and cognitive deficits. Of note, nuclear factor-2 erythroid-2 (Nrf-2) gene silencing and nuclear factor-κB (NF-κB) inhibition studies revealed that caffeine exerted neuroprotection via regulation of Nrf-2- and NF-κB-dependent mechanisms in the HT-22 and BV-2 cell lines, respectively. On the whole, these findings reveal that caffeine rescues Cd-induced oxidative stress-mediated neuroinflammation, neurodegeneration, and memory impairment. The present study suggests that caffeine might be a potential antioxidant and neuroprotective agent against Cd-induced neurodegeneration.

Mice pancreatic islets protection from oxidative stress induced by single-walled carbon nanotubes through naringin

2018 ◽  
Vol 37 (12) ◽  
pp. 1268-1281 ◽  
Author(s):  
A Ahangarpour ◽  
S Alboghobeish ◽  
AA Oroojan ◽  
MA Dehghani
Keyword(s):  
Oxidative Stress ◽  
Carbon Nanotubes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Mtt Assay ◽  
Antioxidant Defense System ◽  
Protective Effects ◽  
Cell Functions

The growing use of carbon nanotubes (CNTs) emphasizes the importance of its potential toxic effects on the human health. Previous studies proved that CNTs caused oxidative stress and decreased cell viability. On the other hand, reactive oxygen species (ROS) and oxidative stress impaired β-cell functions and reduced the insulin secretion. However, there is not any study on the effects of CNTs on islets and β-cells. Therefore, the present study aimed to evaluate the effects of single-walled CNTs (SWCNTs) on oxidative stress in islets in addition to the protective effects of naringin (NRG) as an antioxidant . We examined the effects of SWCNTs and naringin on islets by 3,4 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; measurement of insulin secretion, ROS, and malondialdehyde (MDA); activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) peroxidase (GSH-Px); and content of GSH and mitochondrial membrane potential (MMP). The MTT assay demonstrated that decreased viability of islets cells was dose-dependent with exposure to SWCNTs. Further studies revealed that SWCNTs decreased insulin secretion and MMP, induced the formation of ROS, increased the level of MDA, and decreased the activities of SOD, GSH-Px, and CAT and content of GSH. Furthermore, the pretreatment of islets with naringin significantly reverted back these changes. These findings revealed that SWCNTs might induce the oxidative stress to pancreatic islets, causing the occurrence of diabetes, and the protective effects of naringin that was mediated by augmentation of the antioxidant defense system of islets. Our research indicated the necessity for further in vivo and in vitro researches on the effects of SWCNTs and naringin on diabetes.

174 OXIDATIVE STRESS AND LIPID PEROXIDATION IN BOVINE IN VITRO-PRODUCED EMBRYOS WITH DIFFERENT DEVELOPMENTAL SPEEDS

2012 ◽  
Vol 24 (1) ◽  
pp. 199
Author(s):  
S. Di Francesco ◽  
M. Rubessa ◽  
L. Boccia ◽  
M. De Blasi ◽  
P. Stiuso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Bovine Serum ◽  
Manganese Superoxide Dismutase ◽  
Embryo Viability ◽  
Sod Activity ◽  
Stage Of Development ◽  
Mnsod Activity

In vitro-produced embryos are less viable than their in vivo counterparts. It is known that the developmental speed is a reliable marker of embryo viability. One of the major factors impairing in vitro embryo development is oxidative stress. The aim of the study was to evaluate oxidative stress and lipid peroxidation in bovine in vitro-produced embryos that reached different developmental stages at the end of culture. Abattoir-derived oocytes were matured in vitro in TCM-199 with 15% bovine serum, 0.5 μg mL–1 of FSH, 5 μg mL–1 of LH, 0.8 mM L-glutamine and 50 mg mL–1 of gentamicin. Mature cumulus–oocyte complexes (COC) were fertilized in Tyrode's modified medium, supplemented by 5.3 SI mL–1 of heparin, 30 μM penicillamine, 15 μM hypotaurine, 1 μM epinephrine and 1% of bovine serum. Both in vitro maturation and IVF were carried out at 39°C and 5% CO2 in air. After 20 to 22 h of gamete co-incubation, presumptive zygotes were denuded and cultured in SOF for 7 days at 39°C under humidified air with 5% CO2, 7% O2 and 88% N2 in air. At the end of culture, embryos were assessed according to the stage of development as tight morulae (TM), early blastocysts (eBl), blastocysts (Bl), expanded blastocysts (XBl) and hatched blastocysts (HBl). For each stage of development, an average of 20 embryos were used to determine manganese superoxide dismutase (MnSOD) activity and levels of nitric oxide (NO2–) and thiobarbituric acid-reactive substances (TBARS). The SOD activity was determined by a colourimetric method (Caraglia M et al. 2011 Cell Death Dis. 2, 150, doi:10.1038/cddis.2011.34) whereas NO2– and TBARS were measured by a spectrophotometric method (Balestrieri et al. 2011 J. Cell. Physiol. doi:10.1002/jcp.22874). Data were analysed by t-test. Greater (P < 0.05) MnSOD activity was observed in faster developing embryos (i.e. XBl and HBl) compared with slower ones (i.e. TM, eBl and Bl; 0.46 ± 0.04, 0.46 ± 0.03, 0.14 ± 0.01, 1.66 ± 0.01 and 3.26 ± 0.3 U μg–1 of protein, in TM, eBl, Bl, XBl and HBl, respectively). At the same time, XBl and HBl showed the lowest NO2– levels. However, NO2– values were lower in TM compared with eBl and Bl (0.04 ± 0.002, 0.07 ± 0.005, 0.06 ± 0.003, 0.01 ± 0.002 and 0.01 ± 0.001 nM μg–1 of protein, in TM, eBl, Bl, XBl and HBl, respectively). Similarly to NO2–, TBARS levels were lower in XBl and HBl compared with the other stages (0.0059 ± 0.002, 0.009 ± 0.003, 0.006 ± 0.002, 0.001 ± 0.0001 and 0.0009 ± 0.0002 μM μg–1 of protein, in TM, eBl, Bl, XBl and HBl, respectively). In conclusion, these results clearly indicate developmental stage-dependent changes in MnSOD activity and levels of NO2– and TBARS, suggesting that oxidative stress and lipid peroxidation are reduced in faster developing embryos.

scholarly journals Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan-Yan Meng ◽  
Yu-Pei Yuan ◽  
Xin Zhang ◽  
Chun-Yan Kong ◽  
Peng Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Cell Loss ◽  
Protective Role ◽  
Protective Effects ◽  
Morphological Examination ◽  
Heart Injury ◽  
Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

scholarly journals Protective effect of essential oil of Cinnamomum verum bark on hepatic and renal toxicity induced by carbon tetrachloride in rats

2019 ◽  
Vol 44 (6) ◽  
pp. 606-618 ◽  
Author(s):  
Khaled Bellassoued ◽  
Ferdaws Ghrab ◽  
Houda Hamed ◽  
Rim Kallel ◽  
Jos van Pelt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Essential Oil ◽  
Renal Toxicity ◽  
Density Lipoprotein ◽  
Protein Carbonyl ◽  
Untreated Group ◽  
Protective Effects ◽  
Glutamyl Transferase

The inner bark of cinnamon (Cinnamomum verum) is widely used as a spice. Cinnamon plants are also a valuable source of essential oil used for medicinal purposes. The present study aimed to investigate the composition and in vitro antioxidant activity of essential oil of C. verum bark (CvEO) and its protective effects in vivo on CCl4-induced hepatic and renal toxicity in rats. Groups of animals were pretreated for 7 days with CvEO (70 or 100 mg/kg body weight) or received no treatment and on day 7 a single dose of CCl4 was used to induce oxidative stress. Twenty-four hours after CCl4 administration, the animals were euthanized. In the untreated group, CCl4 induced an increase in serum biochemical parameters and triggered oxidative stress in both liver and kidneys. CvEO (100 mg/kg) caused significant reductions in CCl4-elevated levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein, urea, and creatinine and increased the level of high-density lipoprotein compared with the untreated group. Moreover, pretreatment with CvEO at doses of 70 and 100 mg/kg before administration of CCl4 produced significant reductions in thiobarbituric acid reactive substances and protein carbonyl levels in liver and kidney tissues compared with the untreated group. The formation of pathological hepatic and kidney lesions induced by the administration of CCl4 was strongly prevented by CvEO at a dose of 100 mg/kg. Overall, this study suggests that administration of CvEO has high potential to quench free radicals and alleviate CCl4-induced hepatorenal toxicity in rats.

scholarly journals Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Yan ◽  
Si-Chi Xu ◽  
Chun-Yan Kong ◽  
Xiao-Yang Zhou ◽  
Zhou-Yan Bian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

scholarly journals Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Iwona Zwolak
Keyword(s):  
Oxidative Stress ◽  
Animal Studies ◽  
Toxic Metal ◽  
Protective Effects ◽  
Dietary Antioxidants ◽  
Vanadium Toxicity ◽  
Preventive Effects

Vanadium (V) in its inorganic forms is a toxic metal and a potent environmental and occupational pollutant and has been reported to induce toxic effects in animals and people. In vivo and in vitro data show that high levels of reactive oxygen species are often implicated in vanadium deleterious effects. Since many dietary (exogenous) antioxidants are known to upregulate the intrinsic antioxidant system and ameliorate oxidative stress-related disorders, this review evaluates their effectiveness in the treatment of vanadium-induced toxicity. Collected data, mostly from animal studies, suggest that dietary antioxidants including ascorbic acid, vitamin E, polyphenols, phytosterols, and extracts from medicinal plants can bring a beneficial effect in vanadium toxicity. These findings show potential preventive effects of dietary antioxidants on vanadium-induced oxidative stress, DNA damage, neurotoxicity, testicular toxicity, and kidney damage. The relevant mechanistic insights of these events are discussed. In summary, the results of studies on the role of dietary antioxidants in vanadium toxicology appear encouraging enough to merit further investigations.

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