Protective effect of berberine chloride against cisplatin-induced ototoxicity

Abstract Background Cisplatin (CP) is an effective anticancer drug broadly used for various types of cancers, but it has shown ototoxicity that results from oxidative stress. Berberine has been reported for its anti-oxidative stress suggesting its therapeutic potential for many diseases such as colitis, diabetes, and vascular dementia. Objective Organ of Corti of postnatal day 3 mouse cochlear explants were used to compare hair cells after the treatment with cisplatin alone or with berberine chloride (BC) followed by CP. Methods We investigated the potential of the anti-oxidative effect of BC against the cisplatin-induced ototoxicity. We observed a reduced aberrant bundle of stereocilia in hair cells in CP with BC pre-treated group. Caspase-3 immunofluorescence and TUNEL assay supported the hypothesis that BC attenuates the apoptotic signals induced by CP. Reactive oxygen species level in the mitochondria were investigated by MitoSOX Red staining and the mitochondrial membrane potentials were compared by JC-1 assay. Results BC decreased ROS generation with preserved mitochondrial membrane potentials in mitochondria as well as reduced DNA fragmentation in hair cells. In summary, our data indicate that BC might act as antioxidant against CP by reducing the stress in mitochondria resulting in cell survival. Conclusion Our result suggests the therapeutic potential of BC for prevention of the detrimental effect of CP-induced ototoxicity.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6746907 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 12

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.

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Supplementation of kaempferol to in vitro maturation medium regulates oxidative stress and enhances subsequent embryonic development in vitro

Zygote ◽

10.1017/s0967199419000674 ◽

2019 ◽

Vol 28 (1) ◽

pp. 59-64

Author(s):

Yuhan Zhao ◽

Yongnan Xu ◽

Yinghua Li ◽

Qingguo Jin ◽

Jingyu Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Caspase 3 ◽

Treated Group ◽

Control Group ◽

Oxygen Species

SummaryKaempferol (KAE) is one of the most common dietary flavonols possessing biological activities such as anticancer, anti-inflammatory and antioxidant effects. Although previous studies have reported the biological activity of KAE on a variety of cells, it is not clear whether KAE plays a similar role in oocyte and embryo in vitro culture systems. This study investigated the effect of KAE addition to in vitro maturation on the antioxidant capacity of embryos in porcine oocytes after parthenogenetic activation. The effects of kaempferol on oocyte quality in porcine oocytes were studied based on the expression of related genes, reactive oxygen species, glutathione and mitochondrial membrane potential as criteria. The rate of blastocyst formation was significantly higher in oocytes treated with 0.1 µm KAE than in control oocytes. The mRNA level of the apoptosis-related gene Caspase-3 was significantly lower in the blastocysts derived from KAE-treated oocytes than in the control group and the mRNA expression of the embryo development-related genes COX2 and SOX2 was significantly increased in the KAE-treated group compared with that in the control group. Furthermore, the level of intracellular reactive oxygen species was significantly decreased and that of glutathione was significantly increased after KAE treatment. Mitochondrial membrane potential (ΔΨm) was increased and the activity of Caspase-3 was significantly decreased in the KAE-treated group compared with that in the control group. Taken together, these results suggested that KAE is beneficial for the improvement of embryo development by inhibiting oxidative stress in porcine oocytes.

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Evaluation of Lasting Effects of Heat Stress on Sperm Profile and Oxidative Status of Ram Semen and Epididymal Sperm

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1687657 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 24

Author(s):

Thais Rose dos Santos Hamilton ◽

Camilla Mota Mendes ◽

Letícia Signori de Castro ◽

Patrícia Monken de Assis ◽

Adriano Felipe Perez Siqueira ◽

...

Keyword(s):

Oxidative Stress ◽

Heat Stress ◽

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Treated Group ◽

Epididymal Sperm ◽

Long Term Effects ◽

Stressed Cells

Higher temperatures lead to an increase of testicular metabolism that results in spermatic damage. Oxidative stress is the main factor responsible for testicular damage caused by heat stress. The aim of this study was to evaluate lasting effects of heat stress on ejaculated sperm and immediate or long-term effects of heat stress on epididymal sperm. We observed decrease in motility and mass motility of ejaculated sperm, as well as an increase in the percentages of sperm showing major and minor defects, damaged plasma and acrosome membranes, and a decrease in the percentage of sperm with high mitochondrial membrane potential in the treated group until one spermatic cycle. An increased enzymatic activity of glutathione peroxidase and an increase of stressed cells were observed in ejaculated sperm of the treated group. A decrease in the percentage of epididymal sperm with high mitochondrial membrane potential was observed in the treated group. However, when comparing immediate and long-term effects, we observed an increase in the percentage of sperm with low mitochondrial membrane potential. In conclusion, testicular heat stress induced oxidative stress that led to rescuable alterations after one spermatic cycle in ejaculated sperm and also after 30 days in epididymal sperm.

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Andrographolide Ameliorates Diabetic Cardiomyopathy in Mice by Blockage of Oxidative Damage and NF-κB-Mediated Inflammation

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9086747 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 22

Author(s):

Ershun Liang ◽

Xue Liu ◽

Zhanhui Du ◽

Ruixue Yang ◽

Yuxia Zhao

Keyword(s):

Oxidative Stress ◽

Diabetic Cardiomyopathy ◽

Cardiac Fibrosis ◽

Therapeutic Potential ◽

Myocardial Dysfunction ◽

Underlying Mechanism ◽

Ros Generation ◽

Related Factor

Andrographolide (Andro), a major bioactive component obtained from Andrographis paniculata Nees, has exerted wide antioxidant as well as cytoprotective properties. However, whether Andro treatment could retard the progress of diabetic cardiomyopathy (DCM) remains unknown. In this study, we evaluated the effects of Andro against diabetes-induced myocardial dysfunction and explored the underlying mechanism in STZ-induced diabetic mice. As a result, treatment with Andro dose dependently suppressed cardiac inflammation and oxidative stress, accompanied by decreasing cardiac apoptosis, which subsequently ameliorated cardiac fibrosis and cardiac hypertrophy. Further, Andro blocked hyperglycemia-triggered reactive oxygen species (ROS) generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Our results suggest that the cardioprotective effects afforded by Andro treatment involve the modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. The present study unravels the therapeutic potential of Andro in the treatment of DCM by attenuating oxidative stress, inflammation, and apoptosis.

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The Role of Oxidative Stress and Therapeutic Potential of Antioxidants in Graves’ Ophthalmopathy

Biomedicines ◽

10.3390/biomedicines9121871 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1871

Author(s):

Tzu-Yu Hou ◽

Shi-Bei Wu ◽

Hui-Chuan Kau ◽

Chieh-Chih Tsai

Keyword(s):

Oxidative Stress ◽

Therapeutic Potential ◽

In Vivo Studies ◽

Ros Generation ◽

Ocular Motility ◽

Graves Ophthalmopathy ◽

Antioxidant Supplements

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO.

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Reduction of oxidative stress and apoptosis in hyperlipidemic rats by composite oil (CO) of Sesamum indicum L. and Vicia faba L.

Mediterranean Journal of Nutrition and Metabolism ◽

10.3233/mnm-200500 ◽

2021 ◽

pp. 1-11

Author(s):

Holima Khatun ◽

Mousumi Mitra ◽

Koushik Das ◽

Atiskumar Chattopadhyay ◽

Dilip Kumar Nandi

Keyword(s):

Oxidative Stress ◽

Vicia Faba ◽

Rat Model ◽

Cell Apoptosis ◽

Seed Oil ◽

Treated Group ◽

Ros Generation ◽

Group Iii ◽

Tnf Α ◽

Group Ii

BACKGROUND: Hyperlipidemia associated with cardiovascular diseases (CVDs) is a global health issue that can be alleviated by functional foods. OBJECTIVES: The present study aimed to investigate the effect of composite oil (CO) of sesame seed oil (SSiO) and Vicia faba seed oil (SVfO) on inflammatory factors, ROS generation level, and cell apoptosis level on high lipid diet (HLD) induced hyperlipidemic rat model. METHODS: Hyperlipidemic rat model was developed by feeding HLD to the experimental rats for eight weeks. Male albino rats weighing around 200–210 g were randomly divided into three equal groups: group I: control, received a normal diet; group II: received HLD for eight weeks, group III: received the HLD with CO orally. After 60 days of treatment, the levels of C-reactive protein (CRP), interleukin (IL)-10; tumor necrosis factor (TNF)-α, IL-18, reactive oxygen species (ROS), and cell apoptosis were serially assessed. RESULTS: After eight weeks of CO treatment, TNF- α, IL-18, CRP, and oxidative ROS generation significantly decreased in CO treated group (group III) compared to group II. On the other hand, IL-10 levels significantly increased in CO treated group compared to group II animals. It was also observed that the percentage of the late apoptotic cell reduced considerably in the CO treated group (group III) compared to HLD-fed animals (group II). CONCLUSION: The results indicate that the CO could prevent CVDs via suppressing oxidative stress, ameliorating inflammation and apoptosis in hyperlipidemic rats.

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A Highly Selective In Vitro JNK3 Inhibitor, FMU200, Restores Mitochondrial Membrane Potential and Reduces Oxidative Stress and Apoptosis in SH-SY5Y Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22073701 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3701

Author(s):

Stephanie Cristine Hepp Rehfeldt ◽

Stefan Laufer ◽

Márcia Inês Goettert

Keyword(s):

Oxidative Stress ◽

Membrane Potential ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Neuroprotective Effect ◽

Flow Cytometric Analysis ◽

Unmet Need ◽

Raw264.7 Cells ◽

Ros Generation ◽

Anti Inflammatory

Current treatments for neurodegenerative diseases (ND) are symptomatic and do not affect disease progression. Slowing this progression remains a crucial unmet need for patients and their families. c-Jun N-terminal kinase 3 (JNK3) are related to several ND hallmarks including apoptosis, oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation. JNK inhibitors can play an important role in addressing neuroprotection. This research aims to evaluate the neuroprotective, anti-inflammatory, and antioxidant effects of a synthetic compound (FMU200) with known JNK3 inhibitory activity in SH-SY5Y and RAW264.7 cell lines. SH-SY5Y cells were pretreated with FMU200 and cell damage was induced by 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2). Cell viability and neuroprotective effect were assessed with an MTT assay. Flow cytometric analysis was performed to evaluate cell apoptosis. The H2O2-induced reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm) were evaluated by DCFDA and JC-1 assays, respectively. The anti-inflammatory effect was determined in LPS-induced RAW264.7 cells by ELISA assay. In undifferentiated SH-SY5Y cells, FMU200 decreased neurotoxicity induced by 6-OHDA in approximately 20%. In RA-differentiated cells, FMU200 diminished cell death in approximately 40% and 90% after 24 and 48 h treatment, respectively. FMU200 reduced both early and late apoptotic cells, decreased ROS levels, restored mitochondrial membrane potential, and downregulated JNK phosphorylation after H2O2 exposure. In LPS-stimulated RAW264.7 cells, FMU200 reduced TNF-α levels after a 3 h treatment. FMU200 protects neuroblastoma SH-SY5Y cells against 6-OHDA- and H2O2-induced apoptosis, which may result from suppressing the JNK pathways. Our findings show that FMU200 can be a useful candidate for the treatment of neurodegenerative disorders.

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Significance of Mitochondrial Reactive Oxygen Species in the Generation of Oxidative Stress in Spermatozoa

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2616 ◽

2008 ◽

Vol 93 (8) ◽

pp. 3199-3207 ◽

Cited By ~ 348

Author(s):

Adam J. Koppers ◽

Geoffry N. De Iuliis ◽

Jane M. Finnie ◽

Eileen A. McLaughlin ◽

R. John Aitken

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Complex I ◽

Mitochondrial Membrane ◽

Reactive Oxygen ◽

Human Spermatozoa ◽

Ros Generation ◽

Oxygen Species ◽

Mitochondrial Ros ◽

Sperm Movement

Abstract Context: Male infertility has been linked with the excessive generation of reactive oxygen species (ROS) by defective spermatozoa. However, the subcellular origins of this activity are unclear. Objective: The objective of this study was to determine the importance of sperm mitochondria in creating the oxidative stress associated with defective sperm function. Method: Intracellular measurement of mitochondrial ROS generation and lipid peroxidation was performed using the fluorescent probes MitoSOX red and BODIPY C11 in conjunction with flow cytometry. Effects on sperm movement were measured by computer-assisted sperm analysis. Results: Disruption of mitochondrial electron transport flow in human spermatozoa resulted in generation of ROS from complex I (rotenone sensitive) or III (myxothiazol, antimycin A sensitive) via mechanisms that were independent of mitochondrial membrane potential. Activation of ROS generation at complex III led to the rapid release of hydrogen peroxide into the extracellular space, but no detectable peroxidative damage. Conversely, the induction of ROS on the matrix side of the inner mitochondrial membrane at complex I resulted in peroxidative damage to the midpiece and a loss of sperm movement that could be prevented by the concomitant presence of α-tocopherol. Defective human spermatozoa spontaneously generated mitochondrial ROS in a manner that was negatively correlated with motility. Simultaneous measurement of general cellular ROS generation with dihydroethidium indicated that 68% of the variability in such measurements could be explained by differences in mitochondrial ROS production. Conclusion: We conclude that the sperm mitochondria make a significant contribution to the oxidative stress experienced by defective human spermatozoa.

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Stanozolol treatment decreases the mitochondrial ROS generation and oxidative stress induced by acute exercise in rat skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00790.2010 ◽

2011 ◽

Vol 110 (3) ◽

pp. 661-669 ◽

Cited By ~ 25

Author(s):

Ana Saborido ◽

Alba Naudí ◽

Manuel Portero-Otín ◽

Reinald Pamplona ◽

Alicia Megías

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Fatty Acid Composition ◽

Mitochondrial Membrane ◽

Acute Exercise ◽

Ros Generation ◽

Ros Production ◽

Rat Skeletal Muscle ◽

Mitochondrial Ros ◽

Exercise Induced

Anabolic androgenic steroids are used in the sport context to enhance muscle mass and strength and to increase muscle fatigue resistance. Since muscle fatigue has been related to oxidative stress caused by an exercise-linked reactive oxygen species (ROS) production, we investigated the potential effects of a treatment with the anabolic androgenic steroid stanozolol against oxidative damage induced on rat skeletal muscle mitochondria by an acute bout of exhaustive exercise. Mitochondrial ROS generation with complex I- and complex II-linked substrates was increased in exercised control rats, whereas it remained unchanged in the steroid-treated animals. Stanozolol treatment markedly reduced the extent of exercise-induced oxidative damage to mitochondrial proteins, as indicated by the lower levels of the specific markers of protein oxidation, glycoxidation, and lipoxidation, and the preservation of the activity of the superoxide-sensitive enzyme aconitase. This effect was not due to an enhancement of antioxidant enzyme activities. Acute exercise provoked changes in mitochondrial membrane fatty acid composition characterized by an increased content in docosahexaenoic acid. In contrast, the postexercise mitochondrial fatty acid composition was not altered in stanozolol-treated rats. Our results suggest that stanozolol protects against acute exercise-induced oxidative stress by reducing mitochondrial ROS production, in association with a preservation of mitochondrial membrane properties.

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Use of Radical Oxygen Species Scavenger Nitrones to Treat Oxidative Stress-Mediated Hearing Loss: State of the Art and Challenges

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.711269 ◽

2021 ◽

Vol 15 ◽

Author(s):

Isabel Varela-Nieto ◽

Silvia Murillo-Cuesta ◽

Lourdes Rodríguez-de la Rosa ◽

María Jesús Oset-Gasque ◽

José Marco-Contelles

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Hair Cells ◽

Cell Injury ◽

State Of The Art ◽

Organ Of Corti ◽

Genetic Alterations ◽

Oxygen Species ◽

Radical Oxygen Species ◽

The Subject

Nitrones are potent antioxidant molecules able to reduce oxidative stress by trapping reactive oxygen and nitrogen species. The antioxidant potential of nitrones has been extensively tested in multiple models of human diseases. Sensorineural hearing loss has a heterogeneous etiology, genetic alterations, aging, toxins or exposure to noise can cause damage to hair cells at the organ of Corti, the hearing receptor. Noxious stimuli share a battery of common mechanisms by which they cause hair cell injury, including oxidative stress, the generation of free radicals and redox imbalance. Therefore, targeting oxidative stress-mediated hearing loss has been the subject of much attention. Here we review the chemistry of nitrones, the existing literature on their use as antioxidants and the general state of the art of antioxidant treatments for hearing loss.

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