• Interdisciplinary Bio Central
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• v.3 no.4
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• pp.16.1-16.8
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• 2011

Defects in mitochondrial DNA (mtDNA) cause many human diseases and are critical factors that contribute to aging. The mechanisms of maternally-inherited mtDNA mutations are well studied. However, the role of acquired mutations during the aging process is still poorly understood. The most plausible mechanism is that increased reactive oxygen species (ROS) may affect the opening of mitochondrial voltage dependent anion channel (VDAC) and thus results in damage to mtDNA. This review focuses on recent trends in mtDNA research and the mutations that appear to be associated with increased ROS.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.57-64
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• 2007

Ischemic preconditioning (IPC) is known to protect the heart against ischemia/reperfusion (IR)-induced injuries, and regional differences in the mitochondrial antioxidant state during IR or IPC may promote the death or survival of viable and infarcted cardiac tissues under oxidative stress. To date, however, the interplay between the mitochondrial antioxidant enzyme system and the level of reactive oxygen species (ROS) in the body has not yet been resolved. In the present study, we examined the effects of IR- and IPC-induced oxidative stresses on mitochondrial function in viable and infarcted cardiac tissues. Our results showed that the mitochondria from viable areas in the IR-induced group were swollen and fused, whereas those in the infarcted area were heavily damaged. IPC protected the mitochondria, thus reducing cardiac injury. We also found that the activity of the mitochondrial antioxidant enzyme system, which includes manganese superoxide dismutase (Mn-SOD), was enhanced in the viable areas compared to the infarcted areas in proportion with decreasing levels of ROS and mitochondrial DNA (mtDNA) damage. These changes were also present between the IPC and IR groups. Regional differences in Mn-SOD expression were shown to be related to a reduction in mtDNA damage as well as to the release of mitochondrial cytochrome c (Cyt c). To the best of our knowledge, this might be the first study to explore the regional mitochondrial changes during IPC. The present findings are expected to help elucidate the molecular mechanism involved in IPC and helpful in the development of new clinical strategies against ischemic heart disease.

• The Journal of Internal Korean Medicine
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• v.42 no.6
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• pp.1269-1284
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• 2021

Objectives: Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis Trin., which has been prescribed in traditional Korean medicine to relieve fever and vomiting and to nourish the body fluids. Recently, the protective effect of Phragmitis Rhizoma extract or its components on myelotoxicity and inflammatory responses have been reported, but no study has yet been conducted on oxidative stress. Methods: The present study investigated whether an ethanol extract of Phragmitis Rhizoma (PR) could protect against cellular damage induced by oxidative stress in Chang liver cells. Results: Pretreatment with PR significantly suppressed the hydrogen peroxide (H₂O₂)-induced reduction of Chang cell viability and generation of reactive oxygen species (ROS), thereby deferring apoptosis. PR also markedly inhibited H₂O₂-induced comet tail formation and phospho-γH2AX expression, suggesting that PR protected against oxidative stress-mediated DNA damage. PR also effectively prevented the inhibition of ATP synthesis in H₂O₂-treated Chang cells by inhibiting the loss of mitochondrial membrane potential, indicating that PR maintains energy metabolism through preservation of mitochondrial function while eliminating ROS generated by H₂O₂. Immunoblotting results indicated that PR attenuated the H₂O₂-induced downregulation of Bcl-2 and upregulation of Bax expression. Conclusions: PR protects against oxidative injury in Chang liver cells by regulating energy homeostasis via ROS generation blockade, which is at least partly mediated through inactivation of the mitochondria-mediated apoptosis pathway.

• Journal of Korean Medicine for Obesity Research
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• v.19 no.1
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• pp.1-11
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• 2019

Objectives: The purpose of the present study was to evaluate the preventive effects of ethanol extract of Polygalae radix (EEPR) against oxidative stress (hydrogen peroxide, $H_2O_2$)-induced DNA damage and apoptosis in Chang liver cells. Methods: Chang liver cells were pretreated with various concentrations of EEPR and then challenged with 0.5 mM $H_2O_2$. The cell viability and apoptosis were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis, respectively. The levels of reactive oxygen species (ROS), mitochondrial membrane potentials (MMPs) and adenosine tri-phosphate (ATP) contents were measured. Expression levels of Bcl-2 and Bax were also determined using Western blot analysis. Results: The results showed that the decreased survival rate induced by $H_2O_2$ could be attributed to the induction of DNA damage and apoptosis accompanied by the increased production of ROS, which was remarkably protected by EEPR. In addition, the loss of $H_2O_2$-induced MMPs and ATP contents was significantly attenuated in the presence of EEPR. The inhibitory effect of EEPR on $H_2O_2$-induced apoptosis was associated with up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio. Conclusions: Our data prove that EEPR protects Chang liver cells against $H_2O_2$-induced DNA damage and apoptosis by scavenging ROS and thus suppressing the mitochondrial-dependent apoptosis pathway.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.311-318
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• 2023

Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates oxidative stress-stimulated damage in RPE ARPE-19 cells. Methods: The cytoprotective consequence of CK in hydrogen peroxide (H₂O₂)-treated cells was evaluated by cell viability, DNA damage, and apoptosis assays. Fluorescence analysis and immunoblotting were performed to investigate the inhibitory action of CK on reactive oxygen species (ROS) production and mitochondrial dysfunction. Results: H₂O₂-promoted cytotoxicity, oxidative stress, DNA damage, mitochondrial impairment, and apoptosis were significantly attenuated by CK in ARPE-19 cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation level and its shuttling to the nucleus were increased, which was correlated with upregulated activation of heme oxygenase-1 (HO-1). However, zinc protoporphyrin, a blocker of HO-1, significantly abrogated the preventive action of CK in H₂O₂-treated ARPE-19 cells. Conclusion: This study indicates that activation of Nrf2/HO-1 signaling by CK plays an important role in rescuing ARPE-19 cells from oxidative cellular damage.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.349-360
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• 2024

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H₂O₂) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H₂O₂-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H₂O₂-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H₂O₂-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H₂O₂-mediated calcium (Ca²⁺) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca²⁺-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca²⁺-mediated ER stress by minimizing oxidative stress, thereby inhibiting H₂O₂-induced cytotoxicity in C2C12 myoblasts.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.518-525
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• 2023

Septin4 belong to a family of polymerizing GTP-binding proteins that are required for many cellular functions, such as membrane compartmentalization, vesicular trafficking, mitosis, and cytoskeletal remodeling. Since, Septin4 is expressed specifically in the testis, we aimed to determine the association between Septin4 gene expression with sperm quality, DNA damage, and stress oxidative level in infertile patients. The present study included 60 semen samples that grouped into three groups: normozoospermia (n=20), asthenozoospermia (n=20), astheno-teratozoospermia (n=20). Initially, semen parameters were analyzed by using the World Health Organization protocol. The mRNA expression of Septin4 in sperm was examined using reverse transcription-polymerase chain reaction. Oxidative stress markers, i.e., total antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde, were determined by ELISA kit. The current study showed a statistically significant highly positive correlation in Septin4 gene expression with sperm motility, normal morphology, viability, capacity, and sperm mitochondrial membrane potential (MMP). However, it showed significant negative correlation with sperm DNA fragmentation. Septin4 had a significant correlation with stress oxidative factor and antioxidant enzyme levels. In conclusion, Septin4 gene expression provides clinical useful information for the diagnosis of male infertility. It might be a marker for discrimination between fertile and infertile patients. The current study showed a statistically significant highly positive correlation in Septin4 gene expression with sperm motility, normal morphology, viability, capacity, and sperm MMP. However, it shows significant negative correlation with sperm DNA fragmentation. Septin4 had a significant correlation with stress oxidative factor and antioxidant enzyme levels.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.165-173
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• 2015

Most skin damage caused by ultraviolet B (UVB) radiation is owing to the generation of reactive oxygen species. Phytochemicals can act as antioxidants against UVB-induced oxidative stress. This study investigated the protective effects of the flavone galangin against UVB-induced oxidative damage in human keratinocytes. Galangin efficiently scavenged free radicals and reduced UVB-induced damage to cellular macromolecules, such as DNA, lipids, and proteins. Furthermore, galangin rescued cells undergoing apoptosis induced by UVB radiation via recovering mitochondrial polarization and down-regulating apoptotic proteins. These results showed that galangin protects human keratinocytes against UVB radiation-induced cellular damage and apoptosis via its antioxidant effects.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4517-4525
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• 2016

Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception. The aetiology of childhood cancer and increased disease burden in these children is lin ked to oxidative stress (OS) and oxidative DNA damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the effect of majority of these formulations on DNA is not known. Yoga and meditation cause significant decline in OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene expression and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm ODD as a possible etiological factor in childhood cancer and role of simple life style interventions like yoga and meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing incidence of childhood cancers. Materials and Methods: A total of 131 fathers of children with RB (non-familial sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India. Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index (DFI), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6 months of intervention. We also examined the compliance with yoga and meditation practice and smoking status at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic base 8OHdG, and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affect cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga based life style modification.This may reduce disease burden in next generation and reduce incidence of childhood cancers.

• Journal of Life Science
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• v.31 no.2
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• pp.126-136
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• 2021

Oxidative stress causes injury to and degeneration of retinal pigment epithelial (RPE) cells. It is involved in several retinal disorders and leads to vision loss. In the present study, we investigated the effect of 14 kinds of natural compounds and two kinds of synthetic compounds on oxidative stress-induced cellular damage in human PRE cell lines (ARPE-19). From among them, we selected five kinds of compounds, including auranofin, FK-509, hemistepsin A, honokiol, and spermidine, which have inhibitory effects against hydrogen peroxide (H2O2)-mediated cytotoxicity. In addition, we found that four kinds of compounds (excluding auranofin) have protective effects on H2O2-induced mitochondrial dysfunction. Furthermore, the expression of phosphorylation of histone H2AX, a sensitive marker of DNA damage, was markedly up-regulated by H2O2, whereas it was notably down-regulated by FK-506, honokiol, and spermidine treatment. Meanwhile, five kinds of candidate compounds had no effect on H2O2-induced intracellular reactive oxygen species (ROS) levels, suggesting that the five candidate compounds have protective effects on oxidative stress-induced cellular damage through the ROS-independent pathway. Taken together, according to the results of H2O2-mediated cellular damage―such as cytotoxicity, apoptosis, mitochondrial dysfunction, and DNA damage―spermidine and FK-506 are the natural and synthetic compounds with the most protective effects against oxidative stress in RPE. Although further studies on the identification of the mechanism responsible are required, the results of the present study suggest the possibility of using spermidine and FK-506 to suppress the risk of retinal disorders.