Selenium/Chitosan-Folic Acid Metal Complex Ameliorates Hepatic Damage and Oxidative Injury in Male Rats Exposed to Sodium Fluoride

Continuous exposure to sodium fluoride (NaF) imbalances the oxidative status in the body. The current study investigated the effect of the selenium/chitosan-folic (Se/chitosan-folic acid) novel metal complex on oxidative injury and tissue damage in the hepatic tissues of male rats exposed to (NaF). Male rats received NaF (10.3 mg/kg) and Se/chitosan-folic acid (0.5 mg/Kg) orally for successive 30 days. Male rats exposed to NaF showed multi-histopathological alterations in the hepatic tissues including degenerative changes. NaF exposure elevated hepatic oxidative stress markers, lipid peroxidation, and lowered the antioxidant defense enzymes. Se/chitosan-folic acid novel complex supplementation significantly prevented hepatic injury, suppressed reactive oxygen species (ROS) generation and lipid peroxidation, and enhanced the antioxidant defense enzymes. In addition, Se/chitosan-folic acid supplementation improved the hepatic tissues of NaF-exposed male rats. In conclusion, the Se/chitosan-folic acid novel metal complex protects against NaF-induced oxidative injury and tissue injury in the hepatic tissues of male rats. The Se/chitosan-folic acid novel metal complex upregulated the hepatic tissues and enhanced the antioxidant defense enzymes in male rats.

Synergistic Effects of Curcumin and Nano-Curcumin against Toxicity, Carcinogenicity, and Oxidative Stress Induced by Tartrazine at Normal and Cancer Cell Levels

In this study, the cellular synergistic and antagonistic effects of mixing tartrazine (TZ) with curcumin (CUR) or curcumin-nanoparticles (CUR-NPs) were investigated. The in vivo administration of TZ, CUR, CUR-NPs, and TZ mixed with CUR or CUR-NPs at 75:25 or 50:50 ratios were tested. The results indicated that CUR and CUR -NPs reduced the cytotoxicity effects of TZ on skin fibroblast BJ-1 (ATCC® CRL-2522™) normal cells. However, among the tested materials, CUR-NPs had highest in vitro and in vivo antioxidant activity compared to TZ. Furthermore, CUR-NPs and CUR exhibited anticancer activity against HepG-2 liver cancer cells via apoptosis induction. The key apoptosis protein genes Caspase-3, p53, and Bax were upregulated, whereas Bc-2, which exhibits anti-apoptosis activity, was downregulated. Our results indicated that the nano-formulation of CUR alters its physicochemical properties, including the size and shape, and increases its antioxidant and anticancer properties. CUR-NPs also overcome the side effect of using TZ as a yellow color and food preservative additive, due to its reduced toxicity, oxidative stress, and carcinogenicity. In agreement with our previous findings, CUR and CUR-NPs were able to protect against cellular oxidative stress by stimulating endogenous antioxidant defense enzymes, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST). We conclude that the nano-formulation of CUR exhibits economic benefits as a new strategy to use CUR as a food additive at the cellular level.

Peroxisomal PEX7 Receptor Affects Cadmium-Induced ROS and Auxin Homeostasis in Arabidopsis Root System

Peroxisomes are important in plant physiological functions and stress responses. Through the production of reactive oxygen and nitrogen species (ROS and RNS), and antioxidant defense enzymes, peroxisomes control cellular redox homeostasis. Peroxin (PEX) proteins, such as PEX7 and PEX5, recognize peroxisome targeting signals (PTS1/PTS2) important for transporting proteins from cytosol to peroxisomal matrix. pex7-1 mutant displays reduced PTS2 protein import and altered peroxisomal metabolism. In this research we analyzed the role of PEX7 in the Arabidopsis thaliana root system exposed to 30 or 60 μM CdSO4. Cd uptake and translocation, indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) levels, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels and catalase activity were analyzed in pex7-1 mutant primary and lateral roots in comparison with the wild type (wt). The peroxisomal defect due to PEX7 mutation did not reduce Cd-uptake but reduced its translocation to the shoot and the root cell peroxisomal signal detected by 8-(4-Nitrophenyl) Bodipy (N-BODIPY) probe. The trend of nitric oxide (NO) and peroxynitrite in pex7-1 roots, exposed/not exposed to Cd, was as in wt, with the higher Cd-concentration inducing higher levels of these RNS. By contrast, PEX7 mutation caused changes in Cd-induced hydrogen peroxide (H2O2) and superoxide anion (O2●−) levels in the roots, delaying ROS-scavenging. Results show that PEX7 is involved in counteracting Cd toxicity in Arabidopsis root system by controlling ROS metabolism and affecting auxin levels. These results add further information to the important role of peroxisomes in plant responses to Cd.

Aqueous Extract of Cocoa Phenolic Compounds Protects Differentiated Neuroblastoma SH-SY5Y Cells from Oxidative Stress

Cocoa is a rich source of polyphenols, especially flavanols and procyanidin oligomers, with antioxidant properties, providing protection against oxidation and nitration. Cocoa phenolic compounds are usually extracted with methanol/ethanol solvents in order to obtain most of their bioactive compounds; however, aqueous extraction seems more representative of the physiological conditions. In this study, an aqueous extract of cocoa powder has been prepared and chemically characterized, and its potential protective effect against chemically-induced oxidative stress has been tested in differentiated human neuroblastoma SH-SY5Y cells. Neuronal-like cultured cells were pretreated with realistic concentrations of cocoa extract and its major monomeric flavanol component, epicatechin, and then submitted to oxidative stress induced by a potent pro-oxidant. After one hour, production of reactive oxygen species was evaluated by two different methods, flow cytometry and in situ fluorescence by a microplate reader. Simultaneously, reduced glutathione and antioxidant defense enzymes glutathione peroxidase and glutathione reductase were determined and the results used for a comparative analysis of both ROS (reactive oxygen species) methods and to test the chemo-protective effect of the bioactive products on neuronal-like cells. The results of this approach, never tested before, validate both analysis of ROS and indicate that concentrations of an aqueous extract of cocoa phenolics and epicatechin within a physiological range confer a significant protection against oxidative insult to neuronal-like cells in culture.

Zinc finger protein ZFP36 and pyruvate dehydrogenase kinase PDK1 are key elements in the ABA-mediated aluminum tolerance in rice

Aluminum (Al) toxicity is the major limiting factor for plant production and crop yield on acid soils. Previous works revealed that ZFP36 played a key role in plant adaptation to water stress and rice blast. Here, we report another function of ZFP36, which is associated with detoxification of Al toxicity through abscisic acid (ABA)- dependent mechanism, in rice. Al exposure significantly increased ZFP36 expression level in an ABA-dependent manner. Knocking down ZFP36 triggered Al sensitivity, while overexpressing ZFP36 resulted in an increased Al tolerance. Chromatin immunoprecipitation-sequencing (ChIP-seq), yeast one-hybrid assay, and dual luciferase test revealed that a tonoplast-localized Al transporter, OsALS1, and antioxidant defense enzymes were targeted by ZFP36. Moreover, by combining yeast two-hybrid assay, bimolecular fluorescence complement (BiFC), GST pull-down and in vitro phosphorylation assay, we showed that ZFP36 could interact with and be phosphorylated by the pyruvate dehydrogenase kinase OsPDK1. A strong association was found between the expression, protein content and kinase activity of OsPDK1 with the responses to ABA and Al. Using transgenic plants, we have showed that OsPDK1 could inhibit OsALS1 expression via regulating ZFP36. Overall, our data demonstrates a new ZFP36-controlled mechanism of Al defense in rice plants, which is mediated by OsPDK1.

Hepatoprotective Property of Phyllanthus amarus Alkaloid-Rich Fraction with Respect to Oxidative Stress Marker Enzymes

A disruption in the equilibrium between the generation of reactive oxygen species and antioxidant defense enzymes is referred to as oxidative stress. In the present study, we planned to identify the hepatoprotective effect of Phyllanthus amarus alkaloid rich fraction in wistar strain albino male rats. The hepatic damage was induced by the D-galactosamine and ameliorative effect was tested with alkaloid rich fraction of P. amarus by measuring oxidative stress markers such as G6PDH, LDH, SDH, MDH and GDH in the liver tissue. Activity levels of G6PDH, SDH, MDH and GDH were significantly decreased in D-galactosamine induced hepatitis rats when compare to normal control rat group, while their activities were significantly increased in hepatitis rat group that supplemented with alkaloid rich fraction of P. amarus. In contrast, LDH enzyme activity of liver was significantly increased in the hepatitis rat group when compare to normal control rats, while its activity was significantly decreased in hepatitis rats treated with alkaloid fraction. In conclusion, it is very clear that alkaloid fraction of P. amarus has hepatoprotective property with respect of decreasing oxidative stress by regulating oxidative stress marker enzymes. The isolation and identification of specific alkaloid compounds with hepatoprotective properties and anti-oxidative stress will require much further research.

Evaluation of Hepatoprotective activity of Ethanolic Extract of Garuga pinnata Roxburgh leaves against Carbon tetrachloride induced Hepatotoxicity in rats.

In this study we investigated the in vivo Hepatoprotective activity of ethanolic extract of Garuga pinnata (EEGP) leaves in Carbon tetrachloride (CCl4) induced hepatotoxicity using wistar rats of either sex as model. Hepatotoxicity was induced by the administration of CCl4 intraperitoneally (0.125ml CCl4 in liquid paraffin (1:1) per 100g body weight). Garuga pinnata leaves extract at different dose levels (200 and 400mg/kg, p.o.) showed the dose dependant hepatoprotective effect and was compared with well known standard hepatoprotective Silymarain (100mg/kg). When groups were treated with CCl4, significant increase in serum biochemical parameters such as Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline phosphate (ALP), Acid Phosphate (ACP), Creatinine and alteration of tissue biochemical parameters such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and the total proteins were observed. The histopathological examination of the CCl4 treated groups showed sinusoidal congestion, centrilobular necrosis, marked vacuolations and congestion. However, pretreatment with extract of leaves of Garuga pinnata significantly reduced the increased serum levels of biochemical parameters and restored antioxidant defense enzymes level to its normal. Moreover, histopathology of leaves extract treated groups showed normal architecture with minimal sinusoidal congestion. Taken together, our study concludes that EEGP to be a more potential agent for caring liver from CCl4 induced damage.

CORRECTION OF PSYCHONEUROLOGICAL SIGNS OF ACUTE ALCOHOL INTOXICATION IN RATS WITH A NEW ACETYLCYSTEINE-BASED COMPOSITION

The aim of the study is an experimental confirmation of the use of a new combination of biologically active substances with tonic and antioxidant effects. This combination contains acetylcysteine in its composition to reduce the severity of psychoneurological consequences of alcohol intoxication.Materials and methods. The study was conducted on male Wistar rats. The post-intoxication state was simulated by a single injection of ethanol (3 g/kg, intraperitoneally). Half an hour after awakening, the rats were divided into groups, which were injected with saline, acetylcysteine (1 g/kg), taurine (20 mg/kg), caffeine ( 20 mg/kg), succinic acid (100 mg/kg), lipoic acid (100 mg/kg), pyridoxine (400 mg/kg), or a combination of acetylcysteine with all these substances taken in a twice lower dose (except taurine). Before the treatment and 3 hours after it, the degree of neurological disorders was fixed according to the Combs and D'Alecy scale, in the Open Field test and the Adhesion test. Then the animals were euthanized to assess the level of glutathione, triglycerides and malondialdehyde (MDA) in liver homogenates, to determine the activity of enzymatic antioxidant systems and serum aminotransferases.Results. In the animals injected with alcohol, there were evident signs of neuropsychiatric disorders, manifested in a low motor activity and a decrease in fine motor skills. This state did not change after an oral administration of saline. After the administration of acetylcysteine, taurine, caffeine, succinic and lipoic acids, pyridoxine and, to a greater extent, their compositions, the compensation of neuropsychiatric disorders and improvement of fine motor skills were notified. In the liver of these animals, the levels of glutathione, MDA, triglycerides, and the activity of antioxidant defense enzymes corresponded to the physiological norm.Conclusion. The introduction of a combination of acetylcysteine with taurine, caffeine, pyridoxine, lipoic and succinic acids after an acute alcohol intoxication, to a greater extent than each of the substances separately, contributes to the function retention of the antioxidant system of hepatocytes. Besides, it reduces the level of their dystrophic changes and leads to a decrease in the severity of psychoneurological disturbances in the experimental animals.

Perspectives From Systems Biology to Improve Knowledge of Leishmania Drug Resistance

Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by different Leishmania species and transmitted to humans by sandflies, are among such diseases. Leishmania and other Trypanosomatidae display some peculiar features, which make them a complex system to study. Leishmaniasis chemotherapy is limited due to high toxicity of available drugs, long-term treatment protocols, and occurrence of drug resistant parasite strains. Systems biology studies the interactions and behavior of complex biological processes and may improve knowledge of Leishmania drug resistance. System-level studies to understand Leishmania biology have been challenging mainly because of its unusual molecular features. Networks integrating the biochemical and biological pathways involved in drug resistance have been reported in literature. Antioxidant defense enzymes have been identified as potential drug targets against leishmaniasis. These and other biomarkers might be studied from the perspective of systems biology and systems parasitology opening new frontiers for drug development and treatment of leishmaniasis and other diseases. Our main goals include: 1) Summarize current advances in Leishmania research focused on chemotherapy and drug resistance. 2) Share our viewpoint on the application of systems biology to Leishmania studies. 3) Provide insights and directions for future investigation.

Fucoidan Fractionated from Sargassum coreanum via Step-Gradient Ethanol Precipitation Indicate Promising UVB-Protective Effects in Human Keratinocytes

Fucoidans exhibit a wide range of bioactivities and receive significant attention in functional food and cosmetic research. Industrial applications of fucoidan are limited partially due to high extraction and purification costs. The present study implements an enzyme-assisted extraction and step-gradient ethanol precipitation for fractionating fucoidan from Sargassum coreanum based on its charge and molecular weight and evaluation of ultraviolet B (UVB) protective effects in human keratinocytes (HaCaT). The fucoidan fraction SCOC4 indicated higher fucose and sulfate contents with Fourier-transform infrared and 1H NMR spectral patterns resembling fucoidans. SCOC4 dose-dependently abated UVB-induced keratinocyte damage via suppressing intracellular reactive oxygen species, apoptotic body formation, DNA damage via suppressing mitochondria-mediated apoptosis. UVB-protective effects of SCOC4 were further attributable to the augmentation of nuclear factor erythroid 2-related factor 2 mediated cellular antioxidant defense enzymes. Step-gradient ethanol precipitation was a convenient approach of fractionating fucoidans based on molecular weight and charge (depend on the degree of sulfation). Further evaluation of seasonal variations, biocompatibility parameters, efficacy, and shelf life may widen the use of S. coreanum fucoidans in developing UVB-protective cosmetics and functional foods.