Eduardo Madrigal-Santillán

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.

Betalain, Acid Ascorbic, Phenolic Contents and Antioxidant Properties of Purple, Red, Yellow and White Cactus Pears

Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2-picrylhydrazyl radical-scavenging, protection against oxidation of a β-carotene-linoleic acid emulsion, and iron (II) chelation), the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II)-dependent hydroxyl radicals (OH•), in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p < 0.05) and were lower than the average antiradical activities in red and purple cultivars. The red cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p < 0.05) to the concentration of total phenolic compounds (R2 = 0.90) and ascorbic acid (R2 = 0.86). All 18 cultivars of cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH•.

Antigenotoxic Studies of Different Substances to Reduce the DNA Damage Induced by Aflatoxin B1 and Ochratoxin A

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB1 and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins.

Antigenotoxic Effect of Chamomilla recutita (L.) Rauschert Essential Oil in Mouse Spermatogonial Cells, and Determination of Its Antioxidant Capacity in Vitro

Chamomilla recutita (L.) Rauschert (Asteraceae), popularly known as chamomile, is a plant used in traditional medicine for various therapeutic purposes. Chamomile essential oil (CEO) is particularly known to inhibit the genotoxic damage produced by mutagens in mice somatic cells. The aim of this research was to determine the inhibitory potential of CEO on the genotoxic damage produced by daunorubicin (DAU) in mice germ cells. We evaluated the effect of 5, 50, and 500 mg/kg of essential oil on the rate of sister chromatid exchange (SCE) induced in spermatogonia by 10 mg/kg of the mutagen. We found no genotoxicity of CEO, but detected an inhibition of SCE after the damage induced by DAU; from the lowest to the highest dose of CEO we found an inhibition of 47.5%, 61.9%, and 93.5%, respectively. As a possible mechanism of action, the antioxidant capacity of CEO was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method and ferric thiocyanate assays. In the first test we observed a moderate scavenging potential of the oil; nevertheless, the second assay showed an antioxidant capacity similar to that observed with vitamin E. In conclusion, we found that CEO is an efficient chemoprotective agent against the damage induced by DAU in the precursor cells of the germinal line of mice, and that its antioxidant capacity may induce this effect.

Antioxidant and Anticlastogenic Capacity of Prickly Pear Juice

Plants belonging to the genus Opuntia spp. are the most abundant of the Cactaceae family, grown throughout America and the Mediterranean central area. Its fruit, known as cactus pear or prickly pear, is an oval berry grouped in different colors. Some studies have shown its antioxidant activities which may help in preventing chronic pathologies such as diabetes. The purpose of the study was to evaluate the antioxidant capacity of three varieties of prickly pear juice (red-purple, white-green and yellow-orange) in five different concentrations (100, 250, 500, 750, and 1000 mg/mL) by DPPH (1,1-diphenyl-2-picrylhydrazyl radical) colorimetric method, selecting the best variety to determine its anticlastogenic potential against methyl methanesulfonate (MMS). The results indicate that the highest antioxidant was found in the juice of the prickly pear red-purple variety (PPRP), in all concentrations. Its anticlastogenic potential was therefore evaluated with a micronucleus assay. The experiment was run over two weeks. A negative control was included along with a positive control with MMS (40 mg/kg), a group of mice treated with PPRP (25 mL/kg), and three groups with PPRP (in doses of 25, 16.5 and 8.3 mL/kg) plus the mutagen. The PPRP was administered daily by oral gavage and the MMS was injected intraperitoneally five days prior to the end of the experiment. Blood samples were obtained at 0, 24, 48, 72 and 96 h in order to determine the frequency of micronucleated polychromatic erythrocytes (MNPE). The results indicated that PPRP is not a genotoxic agent, on the contrary, it may reduce the number of MNPE. In this regard, the PPRP showed an anticlastogenic effect directly proportional to its concentrations. Thus, the highest protection was obtained with a concentration of 25 mL/kg after 48 h of treatment.

Lead, Cadmium and Cobalt (Pb, Cd, and Co) Leaching of Glass-Clay Containers by pH Effect of Food

Recent studies have shown that handcrafted glass-clay containers are a health risk because they can be contaminated by heavy metals, which can be transferred to food, thus reaching the human body to potentially cause illness. Therefore, in the present work, we evaluate the leaching of lead, cadmium, and cobalt from glass-clay containers into two types of food: tomato sauce (salsa), and chickpea puree. The containers were obtained from four regions in the Mexican state of Hidalgo. Repetitive extractions from the containers were carried out to quantify the leaching of the heavy metals into the salsa, the chickpea puree, and acetic acid using the technique proposed by the USFDA. The results show that greater use of the containers leads to more leaching of heavy metals into both types of food and into the acetic acid, with the greatest metal extraction recorded for the Ixmiquilpan vessels. These results indicate that the metals present in the glass-clay containers leach into the food and that increased reuse increases the risk to the people who use them in food preparation.

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.