Antiviral and antibacterial properties of phloroglucinols: a review on naturally occurring and (semi)synthetic derivatives with potential therapeutic interest.

Phloroglucinol and derived compounds comprise a huge class of secondary metabolites widely distributed in plants and brown algae. A vast array of biological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer has been associated to this class of compounds. In this review, the available data on the antiviral and antibacterial capacity of phloroglucinols have been analyzed. Some of these compounds and derivatives show important antimicrobial properties in vitro. Phloroglucinols have been shown to be effective against viruses, such as human immunodeficiency virus (HIV), herpes or enterovirus, and preliminary data through docking analysis suggest that they can be effective against SARS-CoV-19. Also, some phloroglucinols derivatives have shown antibacterial effects against diverse bacteria strains, including Bacillus subtilis and Staphylococcus aureus, and (semi)synthetic development of novel compounds have led to phloroglucinols with a significantly increased biological activity. However, therapeutic use of these compounds is hindered by the absence of in vivo studies and scarcity of information on their mechanisms of action, and hence further research efforts are required. On the basis of this consideration, our work aims to gather data regarding the efficacy of natural-occurring and synthetic phloroglucinol derivatives as antiviral and antibacterial agents against human pathogens, which have been published during the last three decades. The recollection of results reported in this review represents a valuable source of updated information that will potentially help researchers in the development of novel antimicrobial agents.

Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation.

SARS-CoV-2 induces a hyperinflammatory reaction due to the excessive release of cytokines during the immune response. The bacterial endotoxin lipopolysaccharide (LPS) contributes to the low-grade inflammation associated with the metabolic syndrome, enhancing the hyperinflammatory reaction induced by the SARS-CoV-2 infection. The intake of sodium nitrate, a precursor of nitrite and nitric oxide, influences the antioxidant and pro-inflammatory gene expression profile after immune stimulation with LPS in peripheral blood mononuclear cells from metabolic syndrome patients. We aimed to assess the inflammatory and antioxidant responses of immune cells from metabolic syndrome patients to exposure to the SARS-CoV-2 spike protein (S protein) together with LPS and the effect of nitrite in these responses. Whole blood samples obtained from six metabolic syndrome patients were cultured for 16 h at 37 °C with four different media: control medium, control medium plus LPS (100 ng/mL), control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL), and control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL) plus nitrite (5 µM). Immune stimulation with the LPS/S protein enhanced nitrate biosynthesis from nitrite oxidation and probably from additional organic precursors. In vitro incubations with the LPS/S protein enhanced the expression and/or release of pro-inflammatory TNFα, IL-6, IL-1ß, and TLR4, as well as the expression of the anti-inflammatory IL-1ra and IL-10 and antioxidant enzymes. Nitrite attenuated the pro- and anti-inflammatory response induced by the S protein without interfering with the activation of TLR4 and antioxidant enzyme expression, raising the possibility that nitrite could have potential as a coadjutant in the treatment of COVID-19.

Phenolic compounds as Nrf2 inhibitors: potential applications in cancer therapy.

Cancer is a leading cause of death worldwide and involves an oxidative stress mechanism. The transcription factor Nrf2 has a crucial role in cytoprotective response against oxidative stress, including cancer growth and progression and therapy resistance. For this reason, inhibitors of Nrf2 are new targets to be studied. Traditional plant-based remedies rich in phytochemicals have been used against human cancers and phenolic compounds are known for their chemopreventive properties. This comprehensive review offers an updated review of the role of phenolic compounds as anticancer agents due to their action on Nrf2 inhibition. In addition, the role of naturally-occurring bioactive anticancer agents are covered in the clinical applications of polyphenols as Nrf2 inhibitors. Video Abstract.

Role of apoptosis and autophagy in mediating tramadol-induced neurodegeneration in the rat hippocampus.

BACKGROUND: Tramadol (TRA) is an analgesic prescribed for treating mild to moderate pains, the abuse of which has increased in recent years. Chronic tramadol consumption produces neurotoxicity, although the mechanisms are unclear. The present study investigated the involvement of apoptosis and autophagy signaling pathways and the mitochondrial system in TRA-induced neurotoxicity. MATERIALS AND METHODS: Sixty adult male Wistar rats were divided into five groups that received standard saline or TRA in doses of 25, 50, 75, 100, or 150 mg/kg intraperitoneally for 21 days. On the 22nd day, the Open Field Test (OFT) was conducted. Jun N-Terminal Kinase (JNK), B-cell lymphoma-2 (Bcl-2), Beclin1, and Bcl-2-like protein 4 (Bax) proteins and tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were measured in rat hippocampal tissue. RESULTS: TRA at doses 75, 100, and 150 mg/kg caused locomotor dysfunction in rats and increased total and phosphorylated forms of JNK and Beclin-1, Bax, and Caspase-3. TRA at the three higher doses also increased the phosphorylated (inactive) form of Bcl-2 level while decreasing the unphosphorylated (active) form of Bcl-2. Similarly, the protein levels of TNF-α and IL-1ß were increased dose-dependently. The mitochondrial respiratory chain enzymes were reduced at the three higher doses of TRA. CONCLUSION: TRA activated apoptosis and autophagy via modulation of TNF-α or IL-1ß/JNK/Bcl-2/Beclin1 and Bcl-2/Bax signaling pathways and dysfunction of mitochondrial respiratory chain enzymes.

Hyperbaric Oxygen Therapy Reduces Oxidative Stress and Inflammation, and Increases Growth Factors Favouring the Healing Process of Diabetic Wounds.

Hyperbaric oxygen therapy (HBOT) is the clinical application of oxygen at pressures higher than atmospheric pressure. HBOT has been effectively used to manage diverse clinical pathologies, such as non-healing diabetic ulcers. The aim of the present study was to analyse the effects of HBOT on the plasma oxidative and inflammation biomarkers and growth factors in patients with chronic diabetic wounds. The participants received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20, before and 2 h after the HBOT. An additional (control) blood sample was collected 28 days after wound recovery. No significant differences were evident in haematological parameters, whereas the biochemical parameters progressively decreased, which was significant for creatine phosphokinase (CPK) and aspartate aminotransferase (AST). The pro-inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin 1ß (IL-1ß), progressively decreased throughout the treatments. Biomarkers of oxidative stress--plasma protein levels of catalase, extracellular superoxide dismutase, myeloperoxidase, xanthine oxidase, malondialdehyde (MDA) levels and protein carbonyls--were reduced in accordance with wound healing. Plasma levels of growth factors--platelet-derived growth factor (PDFG), transforming growth factor ß (TGF-ß) and hypoxia-inducible factor 1-alpha (HIF-1α)-- were increased as a consequence of HBOT and reduced 28 days after complete wound healing, whereas matrix metallopeptidase 9 (MMP9) progressively decreased with the HBOT. In conclusion, HBOT reduced oxidative and pro-inflammatory mediators, and may participate in activating healing, angiogenesis and vascular tone regulation by increasing the release of growth factors.

Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects.

The conventional therapies for cancer have a major concern of poor accessibility to tumor tissues. Furthermore, the requirement of higher doses and non-selective nature of therapeutic are associated with a range of adverse drug reactions (ADRs). However, flavonoids are documented to be effective against various types of cancer, but they are not evaluated for their safety profile and tumor site-specific action. Low solubility, rapid metabolism and poor absorption of dietary flavonoids in gastrointestinal tract hinder their pharmacological potential. Some studies have also suggested that flavonoids may act as pro-oxidant in some cases and may interact with other therapeutic agents, especially through biotransformation. Nanocarriers can alter pharmacokinetics and pharmacodynamic profile of incorporating drug. Moreover, nanocarriers are designed for targeted drug delivery, improving the bioavailability of poorly water-soluble drugs, delivery of macromolecules to site of action within the cell, combining therapeutic agents with imaging techniques which may visualize the site of drug delivery and co-delivery of two or more drugs. Combining two or more anti-cancer agents can reduce ADRs and nanotechnology played a pivotal role in this regard. In vitro and in vivo studies have shown the potential of flavonoids nano-formulations, especially quercetin, naringenin, apigenin, catechins and fisetin in the prevention and treatment of several types of cancer. Similarly, clinical trials have been conducted using flavonoids alone or in combination, however, the nano-formulations effect still needs to be elucidated. This review focuses on the impact of flavonoids nano-formulations on the improvement of their bioavailability, therapeutic and safety profile and will open new insights in the field of drug discovery for cancer therapeutics.

Regulation of DAPK1 by Natural Products: An Important Target in Treatment of Stroke.

Stroke is a sudden neurological disorder that occurs due to impaired blood flow to an area of the brain. Stroke can be caused by the blockage or rupture of a blood vessel in the brain, called ischemic stroke and hemorrhagic stroke, respectively. Stroke is more common in men than women. Atrial fibrillation, hypertension, kidney disease, high cholesterol and lipids, genetic predisposition, inactivity, poor nutrition, diabetes mellitus, family history and smoking are factors that increase the risk of stroke. Restoring blood flow by repositioning blocked arteries using thrombolytic agents or endovascular therapy are the most effective treatments for stroke. However, restoring circulation after thrombolysis can cause fatal edema or intracranial hemorrhage, and worsen brain damage in a process known as ischemia-reperfusion injury. Therefore, there is a pressing need to find and develop more effective treatments for stroke. In the past, the first choice of treatment was based on natural compounds. Natural compounds are able to reduce the symptoms and reduce various diseases including stroke that attract the attention of the pharmaceutical industry. Nowadays, as a result of the numerous studies carried out in the field of herbal medicine, many useful and valuable effects of plants have been identified. The death-associated protein kinase (DAPK) family is one of the vital families of serine/threonine kinases involved in the regulation of some biological functions in human cells. DAPK1 is the most studied kinase within the DAPKs family as it is involved in neuronal and recovery processes. Dysregulation of DAPK1 in the brain is involved in the developing neurological diseases such as stroke. Natural products can function in a variety of ways, including reducing cerebral edema, reducing brain endothelial cell death, and inhibiting TNFα and interleukin-1ß (IL-1ß) through regulating the DAPK1 signal against stroke. Due to the role of DAPK1 in neurological disorders, the aim of this article was to investigate the role of DAPK1 in stroke and its modulation by natural compounds.

Microplastic presence in the pelagic fish, Seriola dumerili, from Balearic Islands (Western Mediterranean), and assessment of oxidative stress and detoxification biomarkers in liver.

Microplastics (MPs) are characterized by their high persistence in marine ecosystems, and due to their small size, they can be easily ingested by very diverse organisms. Although the presence of MPs in wild fish is well documented, there is still limited information on their potential to induce adverse effects. Pelagic fish species, because of their wide distribution, are considered good bioindicators for monitoring environmental pollution of marine ecosystems. This study investigated the presence of MPs in the gastrointestinal tract of the predatory pelagic fish (Seriola dumerili) in the Balearic Islands (Mediterranean Sea), and the possible relationship with oxidative stress through the analysis of biomarkers in liver tissue. The results showed the presence of MPs in 98% of total samples examined (n = 52) with an average of 12.2 ± 1.3 MPs/individual. A greater amount of fibre-like particles was isolated compared to fragments. No correlation between the presence of MPs in the gastrointestinal contents and the size of the fishes was noted. Antioxidant enzymes (superoxide dismutase and catalase) and the phase II detoxification enzyme glutathione-S-transferase showed increased activities in fish with higher MPs load. The activity ethoxyresorufin-O-deethylase and the levels of malondialdehyde were similar in both groups. In conclusion, the present results provide an important database on the assessment of the presence of MP debris in S. dumerili gastrointestinal tract and, the potential capability to cause oxidative stress.

Neurohormetic phytochemicals in the pathogenesis of neurodegenerative diseases.

The world population is progressively ageing, assuming an enormous social and health challenge. As the world ages, neurodegenerative diseases are on the rise. Regarding the progressive nature of these diseases, none of the neurodegenerative diseases are curable at date, and the existing treatments can only help relieve the symptoms or slow the progression. Recently, hormesis has increased attention in the treatment of age-related neurodegenerative diseases. The concept of hormesis refers to a biphasic dose-response phenomenon, where low levels of the drug or stress exert protective of beneficial effects and high doses deleterious or toxic effects. Neurohormesis, as the adaptive aspect of hormetic dose responses in neurons, has been shown to slow the onset of neurodegenerative diseases and reduce the damages caused by aging, stroke, and traumatic brain injury. Hormesis was also observed to modulate anxiety, stress, pain, and the severity of seizure. Thus, neurohormesis can be considered as a potentially innovative approach in the treatment of neurodegenerative and other neurologic disorders. Herbal medicinal products and supplements are often considered health resources with many applications. The hormesis phenomenon in medicinal plants is valuable and several studies have shown that hormetic mechanisms of bioactive compounds can prevent or ameliorate the neurodegenerative pathogenesis in animal models of Alzheimer's and Parkinson's diseases. Moreover, the hormesis activity of phytochemicals has been evaluated in other neurological disorders such as Autism and Huntington's disease. In this review, the neurohormetic dose-response concept and the possible underlying neuroprotection mechanisms are discussed. Different neurohormetic phytochemicals used for the better management of neurodegenerative diseases, the rationale for using them, and the key findings of their studies are also reviewed.

Effects of Human Activity on Markers of Oxidative Stress in the Intestine of Holothuria tubulosa, with Special Reference to the Presence of Microplastics.

Pollution in the seas and oceans is a global problem, which highlights emerging pollutants and plastics, specifically microplastics (MPs), which are tiny (1 µm to 5 mm) ubiquitous plastic particles present in marine environments that can be ingested by a wide range of organisms. Holothurians are benthic organisms that feed on sediment; therefore, they can be exposed to contaminants present in the particles they ingest. The objective was to evaluate the effects of human activity on Holothuria tubulosa through the study of biomarkers. Specimens were collected in three different areas throughout the island of Eivissa, Spain: (1) a highly urbanized area, with tourist uses and a marina; (2) an urbanized area close to the mouth of a torrent; (3) an area devoid of human activity and considered clean. The results showed a higher presence of microplastics (MPs) in the sediments from the highly urbanized area in relation to the other two areas studied. Similarly, a higher number of MPs were observed in the digestive tract of H. tubulosa from the most affected area, decreasing with the degree of anthropic influence. Both in the sediment and in the holothurians, fibers predominated with more than 75% of the items. In the three areas, mesoplastics were analyzed by means of FTIR, showing that the main polymer was polypropylene (27%) followed by low-density polyethylene (17%) and polystyrene (16%). Regarding the biomarkers of oxidative stress, the intestine of H. tubulosa from the most impacted areas showed higher catalase, superoxide dismutase (SOD), glutathione reductase (GRd), and glutathione S-transferase (GST) activities and reduced glutathione (GSH) levels compared to the control area. The intermediate area only presented significant differences in GRd and GST with respect to the clean area. The activities of acetylcholinesterase and the levels and malondialdehyde presented similar values in all areas. In conclusion, human activity evaluated with the presence of MPs induced an antioxidant response in H. tubulosa, although without evidence of oxidative damage or neurotoxicity. H. tubulosa, due to its benthic animal characteristics and easy handling, can be a useful species for monitoring purposes.

Targeting epigenetics in cancer: therapeutic potential of flavonoids.

Irrespective of sex and age, cancer is the leading cause of mortality around the globe. Therapeutic incompliance, unwanted effects, and economic burdens imparted by cancer treatments, are primary health challenges. The heritable features in gene expression that are propagated through cell division and contribute to cellular identity without a change in DNA sequence are considered epigenetic characteristics and agents that could interfere with these features and are regarded as potential therapeutic targets. The genetic modification accounts for the recurrence and uncontrolled changes in the physiology of cancer cells. This review focuses on plant-derived flavonoids as a therapeutic tool for cancer, attributed to their ability for epigenetic regulation of cancer pathogenesis. The epigenetic mechanisms of various classes of flavonoids including flavonols, flavones, isoflavones, flavanones, flavan-3-ols, and anthocyanidins, such as cyanidin, delphinidin, and pelargonidin, are discussed. The outstanding results of preclinical studies encourage researchers to design several clinical trials on various flavonoids to ascertain their clinical strength in the treatment of different cancers. The results of such studies will define the clinical fate of these agents in future.

Epigenetic targeting of cancer stem cells by polyphenols (cancer stem cells targeting).

Epigenetic alterations are one of the main factors that disrupt the expression of genes and consequently, they have an important role in the carcinogenicity and the progression of different cancers. Cancer stem cells (CSCs) are accountable for the recurrence, metastasis, and therapeutic failure of cancer. The noticeable and specific pathways in CSCs can be organized by epigenetic mechanisms such as DNA methylation, chromatin remodeling, regulatory RNAs, among others. Since epigenetics modifications can be changed and reversed, it is a possible tool for cancer control and treatment. Epigenetic therapies against CSCs are emerging as a very new strategy with a good future expectation to treat cancer patients. Phenolic compounds are a vast group of substances with anticarcinogenic functions, antiinflammatory, and antioxidative activities. It seems these characteristics are related to neutralizing CSCs development, their microenvironment, and metabolism through epigenetic mechanisms. In the current work, the types of epigenetic changes known in these cells are introduced. In addition, some studies about the use of polyphenols acting through a variety of epigenetic mechanisms to counteract these cells will be reviewed. The reported results seem to indicate that the use of these phenolic compounds may be useful for CSCs defeat.

Systematic review: Effectiveness of herbal oral care products on ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) resulting from bacterial infection is a prevalent medical problem in intensive care units (ICUs). The purpose of this study was to systematically review available studies on oral products employed to control and reduce VAP in patients undergoing tracheal intubation. This study was based on a systematic review of clinical trial data from science databases such as PubMed, Cochrane, Scopus, and Web of science. Articles were reviewed and selected according to defined criteria and assessed by the primary evaluation checklist. After a critical review of 3,143 search hits, only 18 relevant articles were finally selected for discussion. Our assessment revealed that chlorhexidine and some other oral herbal medications are beneficial in preventing VAP. Chlorhexidine oral dosage forms provide a remarkable role in oral health and prevention of VAP by decreasing the microbial flora in the mouth. Because of similar benefits and comparable effects, some herbal medicines can be suggested as a practical alternative to chlorhexidine.

5-Dodecanolide, a Compound Isolated from Pig Lard, Presents Powerful Anti-Inflammatory Properties.

BACKGROUND: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. METHODS: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). RESULTS: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. CONCLUSIONS: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.

Therapeutic potential of polyphenols in cardiovascular diseases: Regulation of mTOR signaling pathway.

Cardiovascular diseases comprise of non-communicable disorders that involve the heart and/or blood vessels and have become the leading cause of death worldwide with increased prevalence by age. mTOR is a serine/threonine-specific protein kinase which plays a central role in many physiological processes including cardiovascular diseases, and also integrates various proliferative signals, nutrient and energy abundance and stressful situations. mTOR also acts as central regulator during chronic stress, mitochondrial dysfunction and deregulated autophagy which are associated with senescence. Under oxidative stress, mTOR has been reported to exert protective effects regulating apoptosis and autophagy processes and favoring tissue repair. On the other hand, inhibition of mTOR has been suggested to have beneficial effects against atherosclerosis, cardiac hypertrophy and heart failure, and also in extending the lifespan. In this aspect, the use of drugs or natural compounds, which can target mTOR is an interesting approach in order to reduce the number of deaths caused by cardiovascular disease. In the present review, we intend to shed light on the possible effects and molecular mechanism of natural agents like polyphenols via regulating mTOR.

Oral microbiota and Alzheimer's disease: Do all roads lead to Rome?

Alzheimer's disease (AD) is a progressive neurodegenerative pathology affecting milions of people worldwide associated with deposition of senile plaques. While the genetic and environmental risk factors associated with the onset and consolidation of late onset AD are heterogeneous and sporadic, growing evidence also suggests a potential link between some infectious diseases caused by oral microbiota and AD. Oral microbiota dysbiosis is purported to contribute either directly to amyloid protein production, or indirectly to neuroinflammation, occurring as a consequence of bacterial invasion. Over the last decade, the development of Human Oral Microbiome database (HOMD) has deepened our understanding of oral microbes and their different roles during the human lifetime. Oral pathogens mostly cause caries, periodontal disease, and edentulism in aged population, and, in particular, alterations of the oral microbiota causing chronic periodontal disease have been associated with the risk of AD. Here we describe how different alterations of the oral microbiota may be linked to AD, highlighting the importance of a good oral hygiene for the prevention of oral microbiota dysbiosis.

Association between dairy product consumption and hyperuricemia in an elderly population with metabolic syndrome.

BACKGROUND AND AIMS: The prevalence of hyperuricemia has increased substantially in recent decades. It has been suggested that it is an independent risk factor for weight gain, hypertension, hypertriglyceridemia, metabolic syndrome (MetS), and cardiovascular disease. Results from epidemiological studies conducted in different study populations have suggested that high consumption of dairy products is associated with a lower risk of developing hyperuricemia. However, this association is still unclear. The aim of the present study is to explore the association of the consumption of total dairy products and their subtypes with the risk of hyperuricemia in an elderly Mediterranean population with MetS. METHODS AND RESULTS: Baseline cross-sectional analyses were conducted on 6329 men/women (mean age 65 years) with overweight/obesity and MetS from the PREDIMED-Plus cohort. Dairy consumption was assessed using a food frequency questionnaire. Multivariable-adjusted Cox regressions were fitted to analyze the association of quartiles of consumption of total dairy products and their subtypes with the prevalence of hyperuricemia. Participants in the upper quartile of the consumption of total dairy products (multiadjusted prevalence ratio (PR) = 0.84; 95% CI: 0.75-0.94; P-trend 0.02), low-fat dairy products (PR = 0.79; 95% CI: 0.70-0.89; P-trend <0.001), total milk (PR = 0.81; 95% CI: 0.73-0.90; P-trend<0.001), low-fat milk (PR = 0.80; 95% CI: 0.72-0.89; P-trend<0.001, respectively), low-fat yogurt (PR = 0.89; 95% CI: 0.80-0.98; P-trend 0.051), and cheese (PR = 0.86; 95% CI: 0.77-0.96; P-trend 0.003) presented a lower prevalence of hyperuricemia. Whole-fat dairy, fermented dairy, and yogurt consumption were not associated with hyperuricemia. CONCLUSIONS: High consumption of total dairy products, total milk, low-fat dairy products, low-fat milk, low-fat yogurt, and cheese is associated with a lower risk of hyperuricemia.

Perkinsus mediterraneus infection induces oxidative stress in the mollusc Mimachlamys varia.

Perkinsus mediterraneus is a protozoan parasite that can cause marine mollusc diseases known as perkinsosis being a serious threat for clam cultures worldwide. The aim of the present study was first to determine the Perkinsus species infecting the variegated scallop Mimachlamys varia and then to evaluate the existence of oxidative stress in gills of M. varia according to different degrees of infection. DNA sequencing confirmed that P. mediterraneus was the species infecting M. varia. ROS production was progressively increasing with the degree of infection although the differences were only significant in the high-infected group. Low degree of infection significantly increased superoxide dismutase (SOD) and glutathione S-transferase (GST) activities and nitrite levels with respect to the control group. In the high-infected group, a significant increase was evidenced in all analysed enzymes, catalase, SOD, glutathione reductase and GST. Non-significant differences in MDA levels were observed between the control and low-infected groups; however, a significant increase in MDA levels was observed in the high-infected group. In conclusion, the infection by Perkinsus mediterraneus in M. varia induces oxidative stress and an antioxidant response directly related to the infection degree that can contribute to the pathogenicity of the infection.

Combined effects of exposure to sub-lethal concentration of the insecticide chlorpyrifos and the herbicide glyphosate on the biochemical changes in the freshwater crayfish Pontastacus leptodactylus.

Glyphosate is an herbicide that inhibits the growth of weed plants, while chlorpyrifos is an insecticide commonly applied to control the pests' population. This study aimed to investigate the combined effects of chlorpyrifos and glyphosate on biochemical, immunological parameters, and oxidative stress biomarkers in freshwater crayfish Pontastacus leptodactylus for 21 days. The experimental design of this study was factorial (3 × 3), including 0.0, 0.4, and 0.8 mg L-1 glyphosate and 0.0, 2.5, and 5 µg L-1 chlorpyrifos. The exposure to chlorpyrifos, glyphosate alone and a mixture of them significantly decreased acetylcholinesterase, alkaline phosphatase, phenoloxidase activities, and total protein levels. The lactate dehydrogenase, glutamic-pyruvic-transaminase, and catalase activities, the contents of glucose, and malondialdehyde levels were increased in the crayfish. No significant changes were detected in glutamic-oxaloacetic-transaminase (SGOT) activity, triglyceride, and total antioxidant (TAO) levels in the crayfish treated with 0.4 mg L-1 glyphosate and the control group. Co-exposure of crayfish to chlorpyrifos and glyphosate increased SGOT activity and TAO levels. Although chlorpyrifos combined with glyphosate decreased the γ-Glutamyltransferase (GGT) activity, the GGT activity was significantly increased in the P. leptodactylus exposed during 21 days to 5 µg L-1 chlorpyrifos alone and 0.8 mg L-1 glyphosate alone. In comparison with the reference group, no significant changes were evidenced in the cholesterol levels in the P. leptodactylus treated with 2.5 µg L-1 chlorpyrifos, but its levels were significantly increased in the other treatment groups. In conclusion, the mix of glyphosate and chlorpyrifos exhibited synergic effects on the different toxicological biomarkers in the narrow-clawed crayfish. Co-exposure to pesticides may result in disruption of homeostasis in the crayfish by altering the biochemical and immunological parameters.

Evaluation of the status quo of polyphenols analysis: Part I-phytochemistry, bioactivity, interactions, and industrial uses.

Phytochemicals, especially polyphenols, are gaining more attention from both the scientific community and food, pharmaceutical, and cosmetics industries due to their implications in human health. In this line, lately new applications have emerged, and of great importance is the selection of accurate and reliable analytical methods for better evaluation of the quality of the end-products, which depends on diverse process variables as well as on the matrices and on the physicochemical properties of different polyphenols. The first of a two-part review on polyphenols will address the phytochemistry and biological activities of different classes of polyphenols including flavonoids, lignans and flavanolignans, stilbenoids, tannins, curcuminoids, and coumarins. Moreover, the possible interactions of polyphenols and current and potential industrial applications of polyphenols are discussed.