Rodrigo L Castillo

University of Chile · Faculty of Medicine

In heart failure (HF) patients undergoing cardiac surgery, an increased activity of mechanisms related to cardiac remodeling may determine a higher risk of postoperative atrial fibrillation (POAF). Given that atrial fibrillation (AF) has a negative impact on the course and management of HF, including the need for anticoagulation therapy, identifyin...

Aims: Chronic intermittent hypobaric hypoxia (CIHH) exposure due to shift work occurs mainly in 4 × 4 or 7 × 7 days shifts in mining, astronomy, and customs activities, among other institutions. However, the long-lasting effects of CIHH on cardiovascular structure and function are not well characterized. We aimed to investigate the effects of CIHH...

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvat...

Neuroinflammation is a common event in degenerative diseases of the central and peripheral nervous system, triggered by alterations in the immune system or inflammatory cascade. The pathophysiology of these disorders is multifactorial, whereby the therapy available has low clinical efficacy. In this review, it has been postulated the relationship b...

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvat...

Helicobacter pylori has become the causal agent of multiple forms of gastric disease worldwide, including gastric cancer. The enzyme l-asparaginase (ASNase) has been studied as a virulence factor. In this work, we performed an in silico investigation to characterize the immunological profile of H. pylori ASNase (HpASNase) to ascertain the possible...

The systemic effects of oxygen deficiency or excess are not thoroughly described. Knowledge is evolving towards the description of beneficial and detrimental effects of both extremes of partial pressure of oxygen (PaO2). The cellular and tissue mediators derived from the modulation of the oxidative tone and the production of reactive oxygen species...

More than 80 million people live and work (in a chronic or intermittent form) above 2500 masl, and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 100,000 people work in high-altitude shifts, where stays in the lowlands are interspersed with working visits in the highlands. Acute exposure to high altitude has be...

Coronavirus disease 2019 (COVID-19) due to CoV-2 (coronavirus type 2) virus possess a particular risk of developing acute respiratory distress syndrome (ARDS) or SARS (severe acute respiratory syndrome coronavirus 2)-CoV2 in people with pre-existing conditions related to endothelial dysfunction and increased pro-inflammatory and pro-oxidant state....

Background Chronic obstructive pulmonary disease (COPD) is a pathology, which leads to an irreversible and progressive reduction of the airflow, usually caused by smoking, but only present in 25% of smokers. Some mechanisms involved in the onset and progression of the disease are local and systemic factors such as inflammation, exacerbated immune r...

For a high percentage of patients who fail to control their weight just by changing their eating and exercise habits, it is necessary to have drugs that support lifestyle changes. Unfortunately, the history and evolution of pharmacotherapy for the treatment of obesity has been full of dilemmas related to safety, efficacy, abuse and adverse effects....

Ischemia is a severe condition in which blood supply, including oxygen (O), to organs and tissues is interrupted and reduced. This is usually due to a clog or blockage in the arteries that feed the affected organ. Reinstatement of blood flow is essential to salvage ischemic tissues, restoring O, and nutrient supply. However, reperfusion itself may...

The blood circulation interface and the neural tissue feature unique characteristics encompassed by the term blood -brain barrier (BBB). The barrier’s primary functions are maintenance of brain homeostasis, selective transport, and protection, all of them determined by its specialized multicellular structure. The BBB primarily exists at the level o...

Anthracycline-induced cardiotoxicity (AIC) persists as a significant cause of morbidity and mortality in cancer survivors. Although many protective strategies have been evaluated, cardiotoxicity remains an ongoing threat. The mechanisms of AIC remain unclear; however, several pathways have been proposed, suggesting a multifactorial origin. When the...

Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in ob...

Covalent attachment of therapeutic proteins to polyethylene glycol (PEG) is widely used for the improvement of its pharmacokinetic and pharmacological properties, as well as the reduction in reactogenicity and related side effects. This technique named PEGylation has been successfully employed in several approved drugs to treat various diseases, ev...

Introduction: Intermittent hypobaric hypoxia (IHH) is a new relative form of human exposure to high altitude. In Chile, 60000 workers who live at sea level must shift every 5 or 7 days to work in mining prospecting located over 3000 MASL. Pathophysiological effects of chronic and acute hypobaria in humans have been studied extensively and are close...

The development of cryopreservation techniques has led to important changes in animal reproductive biotechnology. However, these techniques are associated with cellular and molecular damage, affecting the mitochondrial function and quality of spermatozoa; moreover studies in fish are limited. In this work, the effects of cryopreservation on ultrast...

Chronic hypobaric hypoxia during fetal and neonatal life induces neonatal pulmonary hypertension. Hypoxia and oxidative stress are driving this condition, which implies an increase generation of reactive oxygen species (ROS) and/or decreased antioxidant capacity. Melatonin has antioxidant properties that decrease oxidative stress and improves pulmo...

More than 140 million people live and works (in a chronic or intermittent form) above 2500 m worldwide and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 55,000 persons work in high altitude shifts, where stays at lowlands and interspersed with working stays at highlands. Acute exposure to high altitude has bee...

Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of...

Supplementary Figure 1: ezetimibe protects againts the increase on total cholesterol in plasma, cholesterol content in heart and heart weight induced by a high cholesterol diet. In rats fed for 4 weeks with control, diet (C), high cholesterol diet (HC) or high cholesterol diet containing 0.001% ezetimibe (HCE) the A) total cholesterol in plasma, B)...

Background Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin...

Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipi...

Hypobaric hypoxia induces DNA damage in rat testicular cells, the production of defective spermatozoids and decreased sperm count, associated with an increase in oxidative stress. 8-Oxoguanine glycosylase (OGG1) enzymes are main members of the base excision repair (BER) system, a DNA repair mechanism. We determined the expression levels of mitochon...

The mechanistic evidence to support the cardioprotective effects of polyunsaturated fatty acids (PUFA) are controversial. The aim was to test cardioprotective mechanisms induced by PUFA supplementation against cardiac ischemia-reperfusion (IR) injury. Ten-week-old male Wistar rats (225 ± 14 g, n = 14) were divided in two groups: rats without supple...

Neurophathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive inter...

Hypoxia is the failure of oxygenation at the tissue level, where the reduced oxygen delivered is not enough to satisfy tissue demands. Metabolic depression is the physiological adaptation associated with reduced oxygen consumption, which evidently does not cause any harm to organs that are exposed to acute and short hypoxic insults. Oxidative stres...

The aim of this study was to determine the gastrointestinal protection by quercetin against indomethacin-induced oxidative stress and inflammation, with specific interest in studying the underlying molecular mechanisms. We hypothesized that the quercetin-protective effect relies on its antioxidant and antiinflammatory properties. Rats were pretreat...

Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute r...

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dys...

Acute Respiratory Failure: Pathophysiological Basis from a Multidisciplinary Clinical Approach Acute Respiratory Failure (ARF) is a syndrome characterized by the inability of the respiratory system to maintain adequate arterial O2 and CO2 levels according to the demands of cellular metabolism. ARF may be caused by the failure of the exchanger, lung...

The development of sperm cryopreservation has enabled transcendental changes to occur in the reproductive biotechnology of both mammals and fish; it has become a basic tool for animal improvement. Nevertheless, these protocols cause damage to cell structure and physiology, altering sperm functioning due to cryoinjuries during freezing and thawing....

Background: Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of t...

Despite continuous advances in the knowledge of breast cancer pathophysiology, this type of neoplasia remains a leading cause of cancer-related death in women worldwide. Carcinogenesis takes a progressive course from somatic mutations, alteration of the DNA repair mechanisms, inhibition of growth suppressors, followed by cell proliferation, tissue...

Intermittent hypobaric hypoxia (IH) is linked with oxidative stress, impairing cardiac function. However, early IH also activate cardio-protective mechanisms. Omega 3 fatty acids (Ω3) induce cardioprotection by reducing infarct size and reinforcing antioxidant defenses. The aim of this work was to determine the combined effects of IH and Ω3 on card...

Background Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of th...

Currently, controversial clinical data about the protective effects in the consumption of n-3 polyunsaturated fatty acids (PUFAs) in ischaemic heart diseases exist. Improved myocardial resistance to ischaemia-reperfusion (IR) injury results in non-lethal myocardial infarction, which is a relevant factor in the myocardial function. We hypothesized t...

Chronic intermittent hypoxia (CIH) induces structural and functional changes in heart, probably associated with ischemia-­‐‑reperfusion (IR), a pathophysiological event linked with excessive reactive oxygen species generation. The cardioprotective effects of polyunsaturated fatty acids (PUFA) have not been well characterized in CIH. The aim of this...

Currently, controversial clinical data about the protective effects in the consumption of n-3 polyunsaturated fatty acids (PUFAs) in ischaemic heart diseases exist. Improved myocardial resistance to ischaemia-reperfusion (IR) injury results in non-lethal myocardial infarction, which is a relevant factor in the myocardial function. We hypothesized t...

Oxidant/antioxidant imbalance has been reported in some infectious diseases, including community-acquired pneumonia (CAP). The aim was to assess the antioxidant status in adults with CAP and its relationship with clinical severity at admission. Fifty-nine patients with CAP were enrolled and categorized at admission by the FINE score, from July 2010...

Reactive oxygen species such as superoxide anion radicals (O2 (-) ) and hydrogen peroxide (H2 O2 ) have for long time been recognized as undesirable by-products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiologi...

This study was designed to assess whether the reinforcement of the antioxidant system, through n-3 fatty acids plus antioxidant vitamin supplementation, could reduce the incidence of postoperative atrial fibrillation. Therapy to prevent postoperative atrial fibrillation remains suboptimal. Despite oxidative stress plays a key role in the pathogenes...

The role of oxidative stress in ischaemic heart disease has been thoroughly investigated in humans. Increased levels of ROS (reactive oxygen species) and RNS (reactive nitrogen species) have been demonstrated during ischaemia and post-ischaemic reperfusion in humans. Depending on their concentrations, these reactive species can act either as benevo...

Oxidative stress and endothelial dysfunction have been associated with essential hypertension (EH) mechanisms. The purpose of this study was to evaluate the effect of carvedilol and nebivolol on the oxidative stress-related parameters and endothelial function in patients with EH. The studied population included 57 patients, either sex, between 30 a...

Sepsis with secondary multisystem organ dysfunction syndrome is the leading cause of death in the pediatric intensive care unit. Increased reactive oxygen species may influence circulating and endothelial cells, contributing to inflammatory tissue injury and explaining the tissue hypoxia paradigm based on microvascular dysfunction. An impaired mito...

Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol t...

Oxidative stress has been strongly involved in the underlying mechanism of atrial fibrillation, particularly in the arrhythmia occurring in patients undergoing cardiac surgery with extracorporeal circulation (postoperative atrial fibrillation). The ischemia/reperfusion injury thus occurring in the myocardial tissue contributes to the development of...

Antecedentes de la investigación: El preacondicionamiento hipóxico se ha utilizado como medida de protección para el miocardio, sin embargo es clínicamente inaplicable. Las especies reactivas de oxígeno (ERO), estarían involucradas en la producción de modificaciones estructurales y eléctricas, que hacen susceptible al tejido auricular a arritmias y...

Background: Oxygen reactive species (ORS) might be involved in structural and electrical changes rendering the atria susceptible to arrhythmias and contractile dysfunction. Aim: to determine the effect of supplementation with omega-3 and vitamins C and E on the anti-oxidative capacity of patients submitted to cardiac surgery with extracorporeal cir...

Atrial fibrillation is the most common complication of cardiac surgical procedures performed with cardiopulmonary bypass. It contributes to increased hospital length of stay and treatment costs. At present, preventive strategies offer only suboptimal benefits, despite improvements in anesthesia, surgical technique, and medical therapy. The pathogen...

Oxidative stress underlies postoperative atrial fibrillation and electrophysiological remodelling associated with rapid atrial pacing. An increasing body of evidence indicates that the formation of reactive oxygen species (ROS) released following extracorporeal circulation are involved in the structural and functional myocardial impairment derived...

Ethanol consumption is known to cause structural and functional renal damage in rat kidney. Acutely, ethanol impairs acid-base regulation, but a chronic effect on urine acidification has not been well elucidated. The aim of the present study was to assess urinary acidification in rats subjected to chronic ethanol consumption and renal function stre...

Wine polyphenols could reinforce the endogenous antioxidant system, thereby diminishing oxidative damage. Studies in chronic models to understand the relationship between the bioavailability of polyphenols and their biological effects are still lacking. The aim of the present study was to prove the hypothesis that the antioxidant capacity of wines...

REV HOSP CLIN UNIV CHILE. Vol. 16 Nº 3 año 2005.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- El Shock Séptico es una importante causa de morbi-mortalidad en pacientes críticos que podría ser explic...

El estrés oxidativo describe un estado de daño causado por las especies reactivas de oxígeno (EROs). Estas representan un tipo de moléculas que derivan del metabolismo del oxígeno y existen en todos los organismos aeróbicos. La mayoría son de origen endógeno y son subproductos de reacciones normales y esenciales, como la generación de energía mitoc...

Antecedentes: La falla renal mioglobinúrica se asocia a estrés oxidativo, lo que podría atenuarse por ingesta de vino. Métodos: Ratas recibieron vino tinto por 10 semanas, los controles sólo bebieron agua. La rabdomiólisis fue causada por inyección intramuscular de glicerol al 50% (10 ml/Kg). Se evaluó la capacidad antioxidante del plasma (FRAP, fe...