Oxidative Stress in Liver Diseases: Pathogenesis,...
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Editorial Oxidative Stress in Liver Diseases: Pathogenesis, Prevention, and Therapeutics Ravirajsinh N. Jadeja, 1 Ranjitsinh V. Devkar, 2 and Srinivas Nammi 3,4 1 Division of Gastroenterology/Hepatology, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA 2 Division of Phytotherapeutics and Metabolic Endocrinology, Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat 390002, India 3 School of Science and Health, Western Sydney University, Penrith, NSW 2751, Australia 4 National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2751, Australia Correspondence should be addressed to Ravirajsinh N. Jadeja; [email protected] Received 28 March 2017; Accepted 29 March 2017; Published 26 April 2017 Copyright © 2017 Ravirajsinh N. Jadeja et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Reactive oxygen species- (ROS-) induced oxidative stress has been implicated in various forms of diseases. Exces- sive ROS generation depletes the endogenous antioxi- dants that subsequently fail to counteract all the ROS leading to cellular injury. Alcohol consumption, high- calorie diet, drug overdose, environmental pollutants, heavy metals, and so forth have been implicated towards manifestation of liver injury via generation of ROS. Hepatocyte mitochondria and endoplasmic reticulum are the major site for ROS generation in various forms of liver diseases. Hence, antioxidants are frequently used to treat oxidative liver injury. Although preclinical results are promising for antioxidant therapy in treating liver diseases, evidences obtained from clinical studies are unclear. Further, detailed investigation on the mechanism of ROS-mediated hepatocyte injury and protective role of antioxidants could provide insight into pathogenesis of hepatocyte injury and open new avenues for diagnosis and development of biomarkers and pharmacological therapies. This special issue is a complication of five preclinical research articles and a review accepted from many submissions following a peer review process. Cholesterol has emerged as a critical player in liver injury. N. Nuño-Lámbarri et al. evaluated the impact of liver choles- terol overload on the progression of the obstructive cholestasis in mice induced by bile duct ligation (BDL) surgery. The results showed that high cholesterol- (HC-) fed mice exhibited augmented oxidative stress and apoptosis along with reduced proliferation of hepatocytes. Further, mortality following BDL was higher in HC-fed mice compared to sham-operated mice. Authors concluded that hepatic cholesterol accumulation impairs hepatocyte regeneration during obstructive cholesta- sis and aggravates the disease with early fatal consequences. In a study by F. Li et al., aged male Sprague Dawley rats were exposed to treadmill training with medium intensity and preatomic analysis of liver extract was carried out. Results obtained from two-dimensional gel electrophoresis followed by MS/MS identification indicated changes in several antioxi- dants. The expression of several proteins involved in key liver metabolic pathways including mitochondrial sulfur, glycolysis, methionine, and protein metabolism was altered compared to that of control rats. These findings indicate that exercise may be beneficial to aged rats through mod- ulation of hepatic protein expression profiles. A beneficial effect of n-3 polyunsaturated fatty acids (PUFAs) in a model of liver disease was evaluated by R. Feng et al. They used fat-1 transgenic mice that synthesize endogenous n-3 from n-6 PUFA. Fat-1 and their WT littermates were exposed to a modified AIN93 diet containing 10% corn oil followed by intraperitoneal injection of a single dose of carbon tetrachloride. Their results showed that severe liver injury in WT mice was remarkably ameliorated in fat-1 mice. They attributed these effects to the activation of Nrf2/keap1 path- way. These findings indicate that n-3 PUFA has potent Hindawi Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 8341286, 2 pages https://doi.org/10.1155/2017/8341286
Transcript of Oxidative Stress in Liver Diseases: Pathogenesis,...
EditorialOxidative Stress in Liver Diseases: Pathogenesis, Prevention, andTherapeutics
Ravirajsinh N. Jadeja,1 Ranjitsinh V. Devkar,2 and Srinivas Nammi3,4
1Division of Gastroenterology/Hepatology, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912, USA2Division of Phytotherapeutics and Metabolic Endocrinology, Department of Zoology, Faculty of Science, The Maharaja SayajiraoUniversity of Baroda, Vadodara, Gujarat 390002, India3School of Science and Health, Western Sydney University, Penrith, NSW 2751, Australia4National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2751, Australia
Correspondence should be addressed to Ravirajsinh N. Jadeja; [email protected]
Received 28 March 2017; Accepted 29 March 2017; Published 26 April 2017
Copyright © 2017 Ravirajsinh N. Jadeja et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reactive oxygen species- (ROS-) induced oxidative stresshas been implicated in various forms of diseases. Exces-sive ROS generation depletes the endogenous antioxi-dants that subsequently fail to counteract all the ROSleading to cellular injury. Alcohol consumption, high-calorie diet, drug overdose, environmental pollutants,heavy metals, and so forth have been implicated towardsmanifestation of liver injury via generation of ROS.Hepatocyte mitochondria and endoplasmic reticulumare the major site for ROS generation in various formsof liver diseases. Hence, antioxidants are frequently usedto treat oxidative liver injury. Although preclinical resultsare promising for antioxidant therapy in treating liverdiseases, evidences obtained from clinical studies areunclear. Further, detailed investigation on the mechanismof ROS-mediated hepatocyte injury and protective role ofantioxidants could provide insight into pathogenesis ofhepatocyte injury and open new avenues for diagnosisand development of biomarkers and pharmacologicaltherapies. This special issue is a complication of fivepreclinical research articles and a review accepted frommany submissions following a peer review process.
Cholesterol has emerged as a critical player in liver injury.N. Nuño-Lámbarri et al. evaluated the impact of liver choles-terol overload on the progression of the obstructive cholestasisin mice induced by bile duct ligation (BDL) surgery. Theresults showed that high cholesterol- (HC-) fedmice exhibited
augmented oxidative stress and apoptosis along with reducedproliferation of hepatocytes. Further,mortality followingBDLwas higher in HC-fedmice compared to sham-operatedmice.Authors concluded that hepatic cholesterol accumulationimpairs hepatocyte regeneration during obstructive cholesta-sis and aggravates the disease with early fatal consequences. Ina study by F. Li et al., aged male Sprague Dawley rats wereexposed to treadmill training with medium intensity andpreatomic analysis of liver extract was carried out. Resultsobtained from two-dimensional gel electrophoresis followedbyMS/MS identification indicated changes in several antioxi-dants. The expression of several proteins involved in keyliver metabolic pathways including mitochondrial sulfur,glycolysis, methionine, and protein metabolism was alteredcompared to that of control rats. These findings indicatethat exercise may be beneficial to aged rats through mod-ulation of hepatic protein expression profiles. A beneficialeffect of n-3 polyunsaturated fatty acids (PUFAs) in amodel of liver disease was evaluated by R. Feng et al. Theyused fat-1 transgenic mice that synthesize endogenous n-3from n-6 PUFA. Fat-1 and their WT littermates wereexposed to a modified AIN93 diet containing 10% corn oilfollowed by intraperitoneal injection of a single dose of carbontetrachloride. Their results showed that severe liver injury inWT mice was remarkably ameliorated in fat-1 mice. Theyattributed these effects to the activation of Nrf2/keap1 path-way. These findings indicate that n-3 PUFA has potent
HindawiOxidative Medicine and Cellular LongevityVolume 2017, Article ID 8341286, 2 pageshttps://doi.org/10.1155/2017/8341286
protective effects against acute liver injury and canbe exploredfor other forms of liver diseases.
The fungus Antrodia cinnamomea (AC) is traditionallybeen used in China for various health benefits. A study byY. Liu et al. not only systematically analyzed the componentsof fermented AC but also demonstrated its protective effectagainst alcohol-induced hepatocyte injury. Treatment ofacute ethanol-intoxicated mice with AC extract significantlyimproved levels of AST and ALT activity, oxidation-relatedenzymes, inflammatory cytokines, and caspases. They alsoconcluded that these effects might be via Akt/NF-κB signal-ing pathway. Garlic is well known for its beneficial effectsagainst many diseases, including liver ailments. A study byF. Zhang et al. evaluated the underlying mechanism forreduced live fibrosis by diallyl trisulfide (DATS), the primaryorganosulfur compound in garlic. The primary rat hepaticstellate cells (HSCs) were treated with hydrogen peroxide(H2O2), and profibrogenic and oxidative stress parameterswere evaluated. The results showed that DATS reducedfibrotic marker expression in HSCs. Further, DATS arrestedcell cycle at G2/M checkpoint associated with downregula-tion of cyclin B1 and cyclin-dependent kinase 1, inducedcaspase-dependent apoptosis, and reduced migration inHSCs. Moreover, intracellular levels of reactive oxygenspecies and lipid peroxide were decreased by DATS. Authorsconcluded that DATS mediated its effects via H2S generation.In hepatocytes, oxidative stress frequently triggers antioxi-dant response by activating nuclear erythroid 2-related factor2 (Nrf2), a transcription factor, which upregulates variouscytoprotective genes. Many studies have highlighted Nrf2 asa potential therapeutic target to treat liver diseases. A reviewarticle by R. N. Jadeja et al. comprehensively appraises vari-ous phytochemicals that have been assessed for their poten-tial to halt acute and chronic liver injury by enhancing theactivation of Nrf2 and have the potential for use in humans.
Acknowledgments
We express our sincere thanks and gratitude to the EditorialBoard of Oxidative Medicine and Cellular Longevity for theirapproval on this concept and continuous help in the success-ful publication of this special issue. We would also like tothank the contributors of this special issue for their scientifi-cally sound paper. With great pleasure and respect, we extendour thanks to the reviewers for the critical assessment of eachpaper, their constructive criticisms, and timely response thatmade this special issue possible.
Ravirajsinh N. JadejaRanjitsinh V. Devkar
Srinivas Nammi
2 Oxidative Medicine and Cellular Longevity
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