Ángel Morales-González

Inflammation, Oxidative Stress, and Obesity

Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.

Hepatoprotective effect of silymarin.

The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum, Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum, which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.

Review of natural products with hepatoprotective effects

The liver is one of the most important organs in the body, performing a fundamental role in the regulation of diverse processes, among which the metabolism, secretion, storage, and detoxification of endogenous and exogenous substances are prominent. Due to these functions, hepatic diseases continue to be among the main threats to public health, and they remain problems throughout the world. Despite enormous advances in modern medicine, there are no completely effective drugs that stimulate hepatic function, that offer complete protection of the organ, or that help to regenerate hepatic cells. Thus, it is necessary to identify pharmaceutical alternatives for the treatment of liver diseases, with the aim of these alternatives being more effective and less toxic. The use of some plants and the consumption of different fruits have played basic roles in human health care, and diverse scientific investigations have indicated that, in those plants and fruits so identified, their beneficial effects can be attributed to the presence of chemical compounds that are called phytochemicals. The present review had as its objective the collecting of data based on research conducted into some fruits (grapefruit, cranberries, and grapes) and plants [cactus pear (nopal) and cactus pear fruit, chamomile, silymarin, and spirulina], which are consumed frequently by humans and which have demonstrated hepatoprotective capacity, as well as an analysis of a resin (propolis) and some phytochemicals extracted from fruits, plants, yeasts, and algae, which have been evaluated in different models of hepatotoxicity.

Detection of cytotoxic activity of lectin on human colon adenocarcinoma (Sw480) and epithelial cervical carcinoma (C33-A).

Lectins comprise a heterogeneous class of proteins that recognize the carbohydrate moieties of glycoconjugates with high specificity. Numerous studies have shown that lectins are capable of recognizing specific carbohydrate moieties displayed by malignant cells or tissues. The present work was performed to investigate the effects of tepary bean (Phaseolus acutifolius) lectins on proliferation, colony formation, and alteration of DNA synthesis of human malignant cells. Tepary bean lectin showed dose dependent effects on the inhibition of viability as well as on colony formation in two human malignant cells lines (C33-A, Sw480); By contrast, tepary bean lectin only showed significant effects on DNA synthesis on Sw480 cells. Our results provide evidence of the anti- proliferative and cytotoxic effects of the tepary bean lectins on C33-A and Sw480 cells lines.

Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

AIM To evaluate the effect of an extract of Geranium schiedeanum (Gs) as a hepatoprotective agent against ethanol (EtOH)-induced toxicity in rats. METHODS Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy (PH); they were then divided into three groups (groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups (2-3) drank an aqueous solution of EtOH (40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances (TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed. RESULTS Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration (restitution liver mass: PH-EtOH group 60.68% vs PH-Gs-EtOH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by EtOH administration appeared to be mitigated by the extract, as observed from the TBARs (PH-EtOH group 200.14 mmol/mg vs PH-Gs-EtOH group 54.20 mmol/mg; P < 0.05), total status of antioxidants (PH-EtOH group 1.43 mmol/L vs PH-Gs-EtOH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination (PH-EtOH group 4.80 mg/g vs PH-Gs-EtOH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals. CONCLUSION The administered extract showed a hepatoprotective effect, limiting the EtOH-induced hepatotoxic effects. This effect can be related to modulating oxido-reduction processes.

What is Known Regarding the Participation of Factor Nrf-2 in Liver Regeneration?

It has been known for years that, after chemical damage or surgical removal of its tissue, the liver initiates a series of changes that, taken together, are known as regeneration, which are focused on the recovery of lost or affected tissue in terms of the anatomical or functional aspect. The Nuclear factor-erythroid 2-related factor (Nrf-2) is a reduction-oxidation reaction (redox)-sensitive transcriptional factor, with the basic leucine Zipper domain (bZIP) motif, encoding the NFE2L2 gene. The Keap1-Nrf2-ARE pathway is transcendental in the regulation of various cellular processes, such as antioxidant defenses, redox equilibrium, the inflammatory process, the apoptotic processes, intermediate metabolism, detoxification, and cellular proliferation. Some reports have demonstrated the regulator role of Nrf-2 in the cellular cycle of the hepatocyte, as well as in the modulation of the antioxidant response and of apoptotic processes during liver regeneration. It has been reported that there is a delay in liver regeneration after Partial hepatectomy (PH) in the absence of Nrf-2, and similarly as a regulator of hepatic cytoprotection due to diverse chemical or biological agents, and in diseases such as hepatitis, fibrosis, cirrhosis, and liver cancer. This regulator/protector capacity is due to the modulation of the Antioxidant response elements (ARE). It is postulated that oxidative stress (OS) can participate in the initial stages of liver regeneration and that Nrf-2 can probably participate. Studies are lacking on the different initiation stages, maintenance, and the termination of liver regeneration alone or with ethanol.

A Comparative Study of Physical and Chemical Processes for Removal of Biomass in Biofilters

After 6 months of operation a long-term biofilter was stopped for two weeks and then it was started up again for a second experimental period of almost 1.3 years, with high toluene loads and submitted to several physical and chemical treatments in order to remove excess biomass that could affect the reactor’s performance due to clogging, whose main effect is a high pressure drop. Elimination capacity and removal efficiency were determined after each treatment. The methods applied were: filling with water and draining, backwashing, and air sparging. Different flows and temperatures (20, 30, 45 and 60 °C) were applied, either with distilled water or with different chemicals in aqueous solutions. Treatments with chemicals caused a decrease of the biofilter performance, requiring periods of 1 to 2 weeks to recover previous values. The results indicate that air sparging with pure distilled water as well as with solutions of NaOH (0.01% w/v) and NaOCl (0.01% w/v) were the treatments that removed more biomass, working either at 20, 30 or 45 °C and at relatively low flow rates (below 320 L h−1), but with a high biodegradation inhibition after the treatments. Dry biomass (g VS) content was determined at three different heights of the biofilter in order to carry out each experiment under the same conditions. The same amount of dry biomass when applying a treatment was established so it could be considered that the biofilm conditions were identical. Wet biomass was used as a control of the biofilter’s water content during treatments. Several batch assays were performed to support and quantify the observed inhibitory effects of the different chemicals and temperatures applied.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequently consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Protective Effect of Silymarin on Liver Damage by Xenobiotics

The liver is the vertebrates’ largest internal organ. It weighs nearly 1.5 kg, is dark red in col‐ or, and is situated in the upper right quadrant of the abdominal cavity. Among the functions that it performs are the following: the metabolism of lipids and carbohydrates, and the syn‐ thesis of proteins, coagulation factors, and biliary salts. Eighty percent of the hepatic paren‐ chyma is made up of hepatocytes, which are the cells mainly responsible for maintaining every function that the liver in its entirety requires to sustain the body’s normal physiologi‐ cal functions in general. In addition to hepatocytes, the liver possesses other cells, such as the so-called Kupffer cells (hepatic macrophages), Ito cells, endothelial cells. The hepato‐ cytes are disposed in the liver in groups denominated lobules, which have a central orifice comprised of the bile duct and by means of which the biliary salts are excreted. The anatom‐ ical loss of the structure of the hepatic lobule is considered a symptom of severe damage to the liver; it can be accompanied by partial or total loss of some physiological function, as in the case of alcohol-related hepatic cirrhosis. [23].

Morphological and biochemical effects of weekend alcohol consumption in rats: Role of concentration and gender

AIM To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats. METHODS Wistar rats weighing 170-200 g were divided into groups as follows: (1) Control groups; and (2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations: (1) Group of males or females with a consumption of a solution of alcohol at 40%; and (2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy. RESULTS In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocellular disorganization CONCLUSION The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.