Oxidative Stress and Inflammation in Hepatic Diseases: Current and Future Therapy.

Liver disease is a highly prevalent disease that is one of the leading causes of death worldwide. The continuous exposure of the liver to some factors such as viruses, alcohol, fat, and biotransformed metabolites can cause hepatic injury, which can lead to inflammation and liver degeneration. When the injury is sustained for long time, it can cause chronic liver diseases (CLDs), which include a spectrum of disease states ranging from simple steatosis and steatohepatitis (steatosis with inflammation and hepatocyte injury and death) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Multiple evidences indicate that oxidative stress and inflammation are the most important pathogenic events in liver diseases regardless of etiology. Oxidative stress and inflammation are not always harmful; they help phagocytes to kill microorganisms and modulate signaling events through redox regulation. However, unregulated and prolonged imbalance in the liver between the production of free radicals and/or reactive oxygen species (ROS) and their elimination by protective mechanisms (antioxidants) leads to damage of important biomolecules and cells, with potential impact on the whole organism causing many chronic diseases. During liver damage, ROS can induce the generation of proinflammatory genes. A critical component of inflammation is the infiltration of inflammatory cells, like neutrophils, monocytes, and lymphocytes, to the site of stimulus. At the site of inflammation, the activated inflammatory cells release chemical mediators (eicosanoids, cytokines, chemokines, nitric oxide, etc.) that induce tissue damage and augmented oxidative stress and reactive species (superoxide, hydrogen peroxide, hydroxyl radical, etc.). Thus, overexpression of the proinflammatory genes provokes an intracellular signaling cascade that produces more ROS, resulting in a vicious cycle, where increased oxidative stress and inflammatory lesion promote the pathogenesis of liver diseases. A better understanding of the basic pathophysiology underlying the development of steatosis, steatohepatitis, fibrosis, cirrhosis, and HCC is needed, so that better treatments can evolve for liver diseases. Thus, this special issue is dedicated to study the implications of the central roles that oxidative stress and inflammation play in CLDs, as well as the associated current and future therapies. Antioxidant and anti-inflammatory therapy has been considered to have the possibility of beneficial effects in the management of liver diseases. In this regard, the group of S. Li et al. from China (in “Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases”) summarize the following: (i) the crucial roles of oxidative stress and inflammation in the development of liver damage and (ii) the relationship and interdependence of these processes and also describe (iii) the different herbal medicines or derived compounds targeting oxidative stress and inflammation in various liver diseases. Also from China, the group of Z. Wang et al. (in “Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets”) provided a review about the development of liver cancer from the perspective of cellular and molecular mechanisms and reported the therapeutic targets of hepatocarcinoma, suggesting that antioxidants are urgently needed to prevent carcinogenesis in the liver. On the other hand, U. S. U. Kumar et al. from Malaysia (in “Redox Control of Antioxidant and Antihepatotoxic Activities of Cassia surattensis Seed Extract against Paracetamol Intoxication in Mice: In Vitro and In Vivo Studies of Herbal Green Antioxidant”) reported the protective effect of Cassia surattensis seed extract against paracetamol-induced liver toxicity in mice and described the antagonist effects of antioxidants during mild colitis. Moreover, the group of R. Chaphalkar et al. from India (in “Antioxidants of Phyllanthus emblica L. Bark Extract Provide Hepatoprotection against Ethanol-Induced Hepatic Damage: A Comparison with Silymarin”) observed that PEE possesses potent antioxidant activity against free radicals and provides significant protection against alcohol-induced liver damage, thus supporting the therapeutic claims made in Ayurveda about Phyllanthus emblica for treatment of hepatic disorders. In recent times, a new puzzle in medical science has appeared: antioxidants may exert either beneficial or harmful effects depending on the cellular requirement for ROS at a particular situation. In this regard, the group of F. A. Moura et al. from Brazil (in “Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats”) observed that N-acetylcysteine is a promising antioxidant toward alleviating ulcerative colitis and hepatotoxicity, but the combination of lipoic acid and N-acetylcysteine in contrast causes hepatic injury and colonic inflammation. Antioxidants and anti-inflammatories also play a crucial role in metabolic liver diseases. From Brazil, A. Paiva et al. (in “Apolipoprotein CIII Overexpression Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death”) demonstrated that persistent hypertriglyceridemia might be more relevant to liver inflammation than intracellular lipid accumulation and that overexpression of apo-CIII increases severity of diet-induced fatty liver disease. This study will be useful to develop new targets to treat metabolic liver diseases. In addition, P. K. Leong and K. M. Ko from China (in “Schisandrin B: A Double-Edged Sword in Nonalcoholic Fatty Liver Disease”) suggest that Schisandrin B, a traditional Chinese herb, may offer potential as a therapeutic agent for NAFLD, due to its antihyperlipidemic, antioxidant, anti-ER stress, anti-inflammatory, and anticarcinogenic activities in cultured hepatocytes in vitro and in rodent livers in vivo. The reduction of oxidative stress is suggested to be one of the main mechanisms to explain the benefits of subnormothermic perfusion against ischemic liver damage. In this regard, T. Carbonell et al. from Spain (in “Subnormothermic Perfusion in the Isolated Rat Liver Preserves the Antioxidant Glutathione and Enhances the Function of the Ubiquitin Proteasome System”) found that subnormothermic perfusion in the liver can induce oxidative stress concomitantly with antioxidant glutathione preservation, triggering antioxidant mechanisms, protecting against ischemic, hypoxic, and toxic damage. In addition, the group of Y. Zhang et al. from China (in “Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation”) suggested that chronic oxidative stress, inflammation, and potential malfunction of antioxidative system are the reasons why hyperglycemia aggravates hepatic ischemia reperfusion injury. Biomarkers are necessary for the evaluation of the severity of oxidative stress in I/R injury; thus, the group of H. Li et al. form China (in “Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia-Reperfusion Injury”) demonstrated that renalase, a ubiquitous flavin adenine dinucleotide-containing amino oxidase, is a sensitive ROS-responsive gene in hepatocytes which can serve as an efficient and sensitive biomarker for the early warning or evaluation of the severity of hepatic I/R injury. Liver diseases remain a significant and major health problem around the world. Current therapies in chronic liver diseases are limited and liver transplantation is the only available treatment for end-stage liver disease. This special issue believes to provide novel, effective, and safe approaches to create future antioxidant and anti-inflammatory therapies for patients with CLDs

Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways.

Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA) that primarily regulates PGC1α and soy protein (SP) that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1) and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c) and their target lipogenic pathway genes via the phosphorylation of 5\u27 adenosine monophosphate-activated protein kinase (AMPK). Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways

Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis

Low- ω

Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA) that primarily regulates PGC1α and soy protein (SP) that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1) and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c) and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK). Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways

LA U INVESTIGA: Revista Científica. Facultad Ciencias de la Salud. Volumen 3. Número 2

En el presente volumen se distinguen varios ámbitos de la investigación en salud desde artículos asociados a la promoción de salud, prevención de enfermedades, así como investigaciones de casos clínicos que evidencia la experiencia del equipo de salud en patologías específicas. Hay que resaltar que muchos de los artículos presentados en el volumen actual corresponden a los resultados de investigaciones ejecutadas en la academia, propias de la Universidad Técnica del Norte y de otras.1._ Melanoma antebraquial derecho metastásico a pa¬red abdominal y pelvis presentación de un caso clínico. 2._ Carcinoma papilar de localizacion extratiroidea. 3._ Tumores del golfo de la yugular 4._ Estudio comparativo del desarrollo psicomotor en niños/as de 1 a 3 años del Centro Infantil del Buen Vivir “CENTRO PUCARA” y “GOTITAS DE AMOR” del cantón Antonio Ante de la provincia de Imbabura. 5._ Adaptaciones de las técnicas comunicacionales al proceso terapéutico de salud mental infantil. 6._ La dinámica de la investigación científica en la formación de los profesionales de enfermería: una aproximación al problema de investigación. 7._ Las agresiones en las parejas de enamorados en la adolescencia y el equilibrio emocional. 8._ Rasgos de personalidad y su influencia en la calidad de vida en los estudiantes de la Unidad Educativa” Las Américas” 9._ Estudio de la postura corporal y su relación con la obesidad y sobrepeso en niños de 6 a 12 años del cantón Antonio Ante de la provincia de Imbabura. 10._ Caracterización de cuidadores informales de personas con discapacidad de la provincia de Im¬babura. 11._ Intervención educativa sobre embarazo en la adolescencia en estudiantes del tercer año de bachillerato de la unidad educativa “Madre Tere¬sa Bacq” Imbabura-Ecuador. 12._ Acceso a la atención de consulta externa de los usuarios del centro de llamadas, que asisten al subcentro de salud San Antonio, Tanguarin Iba¬rra, ecuador 2016. 13._ Prevalencia de disfunción familiar en la parro¬quia urbana de Urcuquí

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas