Showing papers on "Oxidative stress published in 2012"
TL;DR: In this review, the cellular oxidant and antioxidant systems are summarized and the cellular effects and mechanisms of the oxidative stress are discussed.
3,573 citations
TL;DR: This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival, ROS homeostasis and antioxidant gene regulation, mitochondrial oxidative stress, apoptosis, and aging.
3,372 citations
TL;DR: More and more evidence suggests that mROS are critical for healthy cell function, and this evidence is discussed following some background on the generation and regulation ofmROS.
2,038 citations
TL;DR: Recent studies on redox signalling in the regulation of autophagy are highlighted, in the context of the basic mechanisms of mitophagy, and the impact ofautophagy on mitochondrial function and accumulation of reactive species is discussed.
Abstract: Reactive oxygen and nitrogen species change cellular responses through diverse mechanisms that are now being defined. At low levels, they are signalling molecules, and at high levels, they damage organelles, particularly the mitochondria. Oxidative damage and the associated mitochondrial dysfunction may result in energy depletion, accumulation of cytotoxic mediators and cell death. Understanding the interface between stress adaptation and cell death then is important for understanding redox biology and disease pathogenesis. Recent studies have found that one major sensor of redox signalling at this switch in cellular responses is autophagy. Autophagic activities are mediated by a complex molecular machinery including more than 30 Atg (AuTophaGy-related) proteins and 50 lysosomal hydrolases. Autophagosomes form membrane structures, sequester damaged, oxidized or dysfunctional intracellular components and organelles, and direct them to the lysosomes for degradation. This autophagic process is the sole known mechanism for mitochondrial turnover. It has been speculated that dysfunction of autophagy may result in abnormal mitochondrial function and oxidative or nitrative stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is controlled, and the impact of autophagic dysfunction on cellular oxidative stress. The present review highlights recent studies on redox signalling in the regulation of autophagy, in the context of the basic mechanisms of mitophagy. Furthermore, we discuss the impact of autophagy on mitochondrial function and accumulation of reactive species. This is particularly relevant to degenerative diseases in which oxidative stress occurs over time, and dysfunction in both the mitochondrial and autophagic pathways play a role.
1,277 citations
TL;DR: The role of mitochondria in the delayed outcomes of ionization radiation is discussed, and different types of radiation vary in their linear energy transfer (LET) properties, and their effects on various aspects of mitochondrial physiology are discussed.
1,013 citations
TL;DR: Stimulation of mitochondrial function may also prevent NASH development, protecting the cell against the increased flux of reduced substrates to the ETC and ROS generation.
751 citations
TL;DR: The hypothesis that oxidative stress is a crucial player in common neurodegenerative disease is critically assessed and the issues surrounding the failure to translate this hypothesis into an effective clinical treatment are examined.
Abstract: Biological tissues require oxygen to meet their energetic demands. However, the consumption of oxygen also results in the generation of free radicals that may have damaging effects on cells. The brain is particularly vulnerable to the effects of reactive oxygen species due to its high demand for oxygen, and its abundance of highly peroxidisable substrates. Oxidative stress is caused by an imbalance in the redox state of the cell, either by overproduction of reactive oxygen species, or by dysfunction of the antioxidant systems. Oxidative stress has been detected in a range of neurodegenerative disease, and emerging evidence from in vitro and in vivo disease models suggests that oxidative stress may play a role in disease pathogenesis. However, the promise of antioxidants as novel therapies for neurodegenerative diseases has not been borne out in clinical studies. In this review, we critically assess the hypothesis that oxidative stress is a crucial player in common neurodegenerative disease and discuss the source of free radicals in such diseases. Furthermore, we examine the issues surrounding the failure to translate this hypothesis into an effective clinical treatment.
747 citations
TL;DR: ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors, and ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix.
Abstract: Upon reaction with electrons, oxygen is transformed into reactive oxygen species (ROS). It has long been known that ROS can destroy bacteria and destroy human cells, but research in recent decades has highlighted new roles for ROS in health and disease. Indeed, while prolonged exposure to high ROS concentrations may lead to non-specific damage to proteins, lipids, and nucleic acids, low to intermediate ROS concentrations exert their effects rather through regulation of cell signalling cascades. Biological specificity is achieved through the amount, duration, and localisation of ROS production. ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors. ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix. There are multiple sources of ROS, including NADPH oxidase enzymes; similarly, there are a large number of ROS-degrading systems. ROS-related disease can be either due to a lack of ROS (e.g., chronic granulomatous disease, certain autoimmune disorders) or a surplus of ROS (e.g., cardiovascular and neurodegenerative diseases). For diseases caused by a surplus of ROS, antioxidant supplementation has proven largely ineffective in clinical studies, most probably because their action is too late, too little, and too non-specific. Specific inhibition of ROS-producing enzymes is an approach more promising of clinical efficacy.
746 citations
TL;DR: This article looks back to the antioxidant/free radical field in 1994 and discusses how it has progressed in the past 18 years and suggests that increasing endogenous antioxidant levels (e.g., by supplying "pro-oxidants") may be a better approach to therapeutics and disease prevention than consuming large doses of "dietary antioxidants."
Abstract: This article looks back to the antioxidant/free radical field in 1994 and discusses how it has progressed in the past 18 years. In some areas, there has been little change: the role of oxygen radicals and other reactive oxygen species (ROS) in the origin or progression of most human diseases remains uncertain, with cancer and neurodegenerative disease being likely exceptions. Even in diseases in which ROS are involved there has been little progress in developing effective antioxidant treatments. Mega-doses of dietary antioxidants have also generally failed to prevent human disease, in part because they do not decrease oxidative damage in vivo (as revealed by robust biomarkers). However, some strategies that are known to delay disease onset may act, at least in part, by decreasing oxidative damage levels. Nevertheless, far more is known today about endogenous antioxidant defenses and how they are regulated, which has led to a deeper understanding of how some ROS can act as signaling molecules. Increasing endogenous antioxidant levels (e.g., by supplying “pro-oxidants”) may be a better approach to therapeutics and disease prevention than consuming large doses of “dietary antioxidants.”
721 citations
TL;DR: It is demonstrated that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premisedon oxidative stress.
Abstract: We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (Ec) levels with the cellular redox potential (−4.12 to −4.84 eV) was strongly correlated to the ability of Co3O4, Cr2O3, Ni2O3, Mn2O3, and CoO nanoparticles to induce oxygen radicals, oxidative stress, and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single-parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of C57 BL/6 mice. Co3O4, Ni2O3, Mn2O3, and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox ho...
702 citations
TL;DR: A role for p53 in activating necrosis is uncovered and the mitochondrial p53-CypD axis is identified as an important contributor to oxidative stress-induced necrosis and implicates this axis in stroke pathology.
TL;DR: There is strong evidence that mitochondrial dysfunction occurs early and has a primary role in pathogenesis, and several mitochondrial diseases as models of neurodegeneration are discussed.
TL;DR: The results demonstrate that HepG2 cells exposed to 14–20 μg/ml ZnO nanoparticles for 12 h showed a decrease in cell viability and the mode of cell death induced by Zn O nanoparticles was apoptosis, and apoptosis was found to be independent of JNK and p38 pathways.
Abstract: The wide scale use of Zinc oxide (ZnO) nanoparticles in the world consumer market makes human beings more prone to the exposure to ZnO nanoparticles and its adverse effects. The liver, which is the primary organ of metabolism, might act as a major target organ for ZnO nanoparticles after they gain entry into the body through any of the possible routes. Therefore, the aim of the present study was to assess the apoptotic and genotoxic potential of ZnO nanoparticles in human liver cells (HepG2) and the underlying molecular mechanism of its cellular toxicity. The role of dissolution in the toxicity of ZnO nanoparticles was also investigated. Our results demonstrate that HepG2 cells exposed to 14–20 μg/ml ZnO nanoparticles for 12 h showed a decrease in cell viability and the mode of cell death induced by ZnO nanoparticles was apoptosis. They also induced DNA damage which was mediated by oxidative stress as evidenced by an increase in Fpg sensitive sites. Reactive oxygen species triggered a decrease in mitochondria membrane potential and an increase in the ratio of Bax/Bcl2 leading to mitochondria mediated pathway involved in apoptosis. In addition, ZnO nanoparticles activated JNK, p38 and induced p53Ser15 phosphorylation. However, apoptosis was found to be independent of JNK and p38 pathways. This study investigating the effects of ZnO nanoparticles in human liver cells has provided valuable insights into the mechanism of toxicity induced by ZnO nanoparticles.
TL;DR: Recent advances in the studies of the relation between oxidative stress, lipid peroxidation products, and cancer progression are focused on, with particular attention to the pro-oxidant anticancer agents and the drug-resistant mechanisms, which could be modulated to obtain a better response to cancer therapy.
Abstract: The generation of reactive oxygen species (ROS) and an altered redox status are common biochemical aspects in cancer cells. ROS can react with the polyunsaturated fatty acids of lipid membranes and induce lipid peroxidation. The end products of lipid peroxidation, 4-hydroxynonenal (HNE), have been considered to be a second messenger of oxidative stress. Beyond ROS involvement in carcinogenesis, increased ROS level can inhibit tumor cell growth. Indeed, in tumors in advanced stages, a further increase of oxidative stress, such as that occurs when using several anticancer drugs and radiation therapy, can overcome the antioxidant defenses of cancer cells and drive them to apoptosis. High concentrations of HNE can also induce apoptosis in cancer cells. However, some cells escape the apoptosis induced by chemical or radiation therapy through the adaptation to intrinsic oxidative stress which confers drug resistance. This paper is focused on recent advances in the studies of the relation between oxidative stress, lipid peroxidation products, and cancer progression with particular attention to the pro-oxidant anticancer agents and the drug-resistant mechanisms, which could be modulated to obtain a better response to cancer therapy.
TL;DR: This review presents as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress to present a variety of therapeutic strategies designed to address these pathological processes.
TL;DR: The signaling pathways of this integrated network through which AMPK controls energy metabolism, autophagic degradation and stress resistance and ultimately the aging process are reviewed.
01 Jan 2012
TL;DR: Recent researches on the mechanisms and possible regulatory roles of ROS in abiotic stress tolerance are summarized to discuss the progress made during the last few decades in improving the oxidative stress tolerance of plants through genetic engineering by different components of ROS detoxification systems in plants.
Abstract: In a persistently changing environment, plants are constantly challenged by various abiotic stresses such as salinity, drought, temperature extremes, heavy metal toxicity, high-light intensity, nutrient deficiency, UV-B radiation, ozone, etc. which cause substantial losses in the yield and quality of a crop. A key sign of such stresses at the molecular level is the accelerated production of reactive oxygen species (ROS) such as singlet oxygen (1O2), superoxide (O2•−), hydrogen peroxide (H2O2) and hydroxyl radicals (OH•). ROS are extremely reactive in nature because they can interact with a number of cellular molecules and metabolites, thereby leading to irreparable metabolic dysfunction and death. Plants have well-developed enzymatic and non-enzymatic scavenging pathways or detoxification systems to counter the deleterious effects of ROS that include the enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPX) and peroxidases (POX) as well as non-enzymatic compounds such as ascorbate (AsA), glutathione (GSH), carotenoids and tocopherols. In plant cells, specific ROS-producing and scavenging systems are found in different organelles and the ROS-scavenging pathways from different cellular compartments are coordinated. Recent studies in plants have shown that relatively low levels of ROS act as signaling molecules that induce abiotic stress tolerance by regulating the expression of defense genes. Additionally, numerous results have shown that plants with higher levels of antioxidants, whether constitutive or induced, showed greater resistance to different types of environmental stresses. In this chapter we attempt to summarize recent researches on the mechanisms and possible regulatory roles of ROS in abiotic stress tolerance. Further, we discuss the progress made during the last few decades in improving the oxidative stress tolerance of plants through genetic engineering by different components of ROS detoxification systems in plants.
TL;DR: The nature of ROS-induced damage on key cellular targets of oxidative stress is examined and evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity is reviewed.
Abstract: Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.
TL;DR: This review will focus on understanding the relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy to help elucidate the question of which comes first in the progression of diabetic neophropathy, oxidative stress, or inflammation.
Abstract: The prevalence of diabetes has dramatically increased worldwide due to the vast increase in the obesity rate. Diabetic nephropathy is one of the major complications of type 1 and type 2 diabetes and it is currently the leading cause of end-stage renal disease. Hyperglycemia is the driving force for the development of diabetic nephropathy. It is well known that hyperglycemia increases the production of free radicals resulting in oxidative stress. While increases in oxidative stress have been shown to contribute to the development and progression of diabetic nephropathy, the mechanisms by which this occurs are still being investigated. Historically, diabetes was not thought to be an immune disease; however, there is increasing evidence supporting a role for inflammation in type 1 and type 2 diabetes. Inflammatory cells, cytokines, and profibrotic growth factors including transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), connective tissue growth factor (CTGF), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-18 (IL-18), and cell adhesion molecules (CAMs) have all been implicated in the pathogenesis of diabetic nephropathy via increased vascular inflammation and fibrosis. The stimulus for the increase in inflammation in diabetes is still under investigation; however, reactive oxygen species are a primary candidate. Thus, targeting oxidative stress-inflammatory cytokine signaling could improve therapeutic options for diabetic nephropathy. The current review will focus on understanding the relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy to help elucidate the question of which comes first in the progression of diabetic nephropathy, oxidative stress, or inflammation.
TL;DR: The importance of endogenous antioxidant defense systems, their relationship to several pathophysiological processes and their possible therapeutic implications in vivo are described.
Abstract: Diabetes is considered to be one of the most common chronic diseases worldwide. There is a growing scientific and public interest in connecting oxidative stress with a variety of pathological conditions including diabetes mellitus (DM) as well as other human diseases. Previous experimental and clinical studies report that oxidative stress plays a major role in the pathogenesis and development of complications of both types of DM. However, the exact mechanism by which oxidative stress could contribute to and accelerate the development of complications in diabetic mellitus is only partly known and remains to be clarified. On the one hand, hyperglycemia induces free radicals; on the other hand, it impairs the endogenous antioxidant defense system in patients with diabetes. Endogenous antioxidant defense mechanisms include both enzymatic and non-enzymatic pathways. Their functions in human cells are to counterbalance toxic reactive oxygen species (ROS). Common antioxidants include the vitamins A, C, and E, glutathione (GSH), and the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GRx). This review describes the importance of endogenous antioxidant defense systems, their relationship to several pathophysiological processes and their possible therapeutic implications in vivo.
TL;DR: It is suggested that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.
Abstract: Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs—but not either treatment alone—resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.
TL;DR: A mechanism-based strategy to therapeutically suppress atherosclerosis progression and its clinical sequelae is suggested, suggesting a protective process in oxidatively stressed macrophages relevant to plaque necrosis.
TL;DR: The introduction of molecular oxygen into the atmosphere was accompanied by the generation of reactive oxygen species (ROS) as side products of many biochemical reactions.
Abstract: The introduction of molecular oxygen into the atmosphere was accompanied by the generation of reactive oxygen species (ROS) as side products of many biochemical reactions. ROS are permanently generated in plastids, peroxisomes, mitochiondria, the cytosol and the apoplast. Imbalance between ROS generation and safe detoxification generates oxidative stress and the accumulating ROS are harmful for the plants. On the other hand, specific ROS function as signaling molecules and activate signal transduction processes in response to various stresses. Here, we summarize the generation of ROS in the different cellular compartments and the signaling processes which are induced by ROS.
TL;DR: The major hallmark of cellular senescence is an irreversible cell cycle arrest and thus it is a potent tumor suppressor mechanism and emerging data has revealed that NF-κB signaling is the major signaling pathway which stimulates the appearance of SASP.
TL;DR: Evidence supporting the notion that peroxisomal metabolism and oxidative stress are intimately interconnected and associated with age-related diseases is discussed.
TL;DR: How the biogenesis and remodelling of mitochondria that are elicited by PGC1&agr; contribute to an increase in oxidative metabolism and the preservation of ROS homeostasis is discussed and the importance in ageing and neurodegenerative disorders is examined.
Abstract: PGC1α is a transcriptional coactivator that is a central inducer of mitochondrial biogenesis in cells. Recent work highlighted that PGC1α can also modulate the composition and functions of individual mitochondria. Therefore, it is emerging that PGC1α is controlling global oxidative metabolism by performing two types of remodelling: (1) cellular remodelling through mitochondrial biogenesis, and (2) organelle remodelling through alteration in the intrinsic properties of mitochondria. The elevated oxidative metabolism associated with increased PGC1α activity could be accompanied by an increase in reactive oxygen species (ROS) that are primarily generated by mitochondria. However, increasing evidence suggests that this is not the case, as PGC1α is also a powerful regulator of ROS removal by increasing the expression of numerous ROS-detoxifying enzymes. Therefore, PGC1α, by controlling both the induction of mitochondrial metabolism and the removal of its ROS by-products, would elevate oxidative metabolism and minimize the impact of ROS on cell physiology. In this Commentary, we discuss how the biogenesis and remodelling of mitochondria that are elicited by PGC1α contribute to an increase in oxidative metabolism and the preservation of ROS homeostasis. Finally, we examine the importance of these findings in ageing and neurodegenerative disorders, conditions that are associated with impaired mitochondrial functions and ROS balance.
TL;DR: Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.
Abstract: Parkinson’s disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1 )a ndLRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q10, rapamycin, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSCderived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.
TL;DR: The highest ratio was observed in retinoblastoma patients and the lowest in anaplastic ependymoma, and the results were able to distinguish between the diagnoses based on the results of the obtained GSH:GSSG ratio.
Abstract: Oxidative stress causes profound alterations of various biological structures, including cellular membranes, lipids, proteins and nucleic acids, and it is involved in numerous malignancies. Reduced glutathione (GSH) is considered to be one of the most important scavengers of reactive oxygen species (ROS), and its ratio with oxidised glutathione (GSSG) may be used as a marker of oxidative stress. The main aim of this study was to determine GSH:GSSG ratio in the blood serum of paediatric cancer patients to use this ratio as a potential marker of oxidative stress. The whole procedure was optimised and the recoveries for both substances were greater than 80% under the optimised conditions. We analysed a group of paediatric patients (n=116) with various types of cancer, including neuroblastoma, anaplastic ependymoma, germ cell tumour, genital tract tumour, lymphadenopathy, rhabdomyosarcoma, nephroblastoma, Ewing's sarcoma, osteosarcoma, Hodgkin's lymphoma, medulloblastoma and retinoblastoma. We simultaneously determined the levels of reduced and oxidised glutathione, and thus, its ratio in the blood serum of the patients. The highest ratio was observed in retinoblastoma patients and the lowest in anaplastic ependymoma. We were able to distinguish between the diagnoses based on the results of the obtained GSH:GSSG ratio.
TL;DR: There is substantial overlap between diabetes and hypertension in etiology and disease mechanisms and knowing the common causes and disease mechanism allows a more effective and proactive approach in their prevention and treatment.
Abstract: Diabetes and hypertension frequently occur together. There is substantial overlap between diabetes and hypertension in etiology and disease mechanisms. Obesity, inflammation, oxidative stress, and insulin resistance are thought to be the common pathways. Recent advances in the understanding of these pathways have provided new insights and perspectives. Physical activity plays an important protective role in the two diseases. Knowing the common causes and disease mechanisms allows a more effective and proactive approach in their prevention and treatment.
TL;DR: A review of recent concepts in OS, antioxidants and the molecular pathways involved in hepatic fibrosis highlights new molecular targets with therapeutic potential for more targeted and personalized control of this disease.
Abstract: Liver fibrosis represents a health problem with significant morbidity and mortality that affects 100 million people worldwide. It is a final pathway to several chronic liver diseases and is characterized by excess collagen and accumulation of extracellular matrix in response to chronic hepatocellular damage. Clinical and experimental data suggest that oxidative stress (OS) mediates the progression of fibrosis, and that OS-related molecules may act as mediators of molecular and cellular events implicated in liver fibrosis. The generation of reactive oxygen species (ROS) plays an important role in producing liver damage and initiating hepatic fibrogenesis. OS disrupts lipids, proteins and DNA, induces necrosis and apoptosis of hepatocytes and amplifies the inflammatory response. ROS also stimulate the production of profibrogenic mediators from Kupffer cells and circulating inflammatory cells and directly activate hepatic stellate cells, resulting in the initiation of fibrosis. Advances in understanding the mechanisms involved in fibrosis have identified new molecular targets with therapeutic potential for more targeted and personalized control of this disease. This review will highlight recent concepts in OS, antioxidants and the molecular pathways involved in hepatic fibrosis.