Initiation and Prevention of Biological Damage by Radiation-Generated Protein Radicals

Ionizing radiations cause chemical damage to proteins. In aerobic aqueous solutions, the damage is commonly mediated by the hydroxyl free radicals generated from water, resulting in formation of protein radicals. Protein damage is especially significant in biological systems, because proteins are the most abundant targets of the radiation-generated radicals, the hydroxyl radical-protein reaction is fast, and the damage usually results in loss of their biological function. Under physiological conditions, proteins are initially oxidized to carbon-centered radicals, which can propagate the damage to other molecules. The most effective endogenous antioxidants, ascorbate, GSH, and urate, are unable to prevent all of the damage under the common condition of oxidative stress. In a promising development, recent work demonstrates the potential of polyphenols, their metabolites, and other aromatic compounds to repair protein radicals by the fast formation of less damaging radical adducts, thus potentially preventing the formation of a cascade of new reactive species.

Attenuation of the onset and progression of age-related vision impairments by reducing oxidative stress and inflammation by micronutrients

The major eye diseases refractive error, cataract, age-related macular degeneration (ARMD), glaucoma, and diabetic retinopathy can lead to blindness without an early intervention. The treatments include eye glasses for refractive error, surgery for cataract, and medications for glaucoma and ARMD. These therapies do not address oxidative stress and inflammation that contribute to these eye diseases. Therefore, supplementation with antioxidants could be useful. However, administration with single or multiple dietary antioxidants with or without carotenoids (zeaxanthin and lutein), and omega-3-fatty acids, produced no benefits or only modest benefits in certain eye diseases. The problems associated with such antioxidant’s approaches were identified, and potential causes for not producing optimal benefits were presented. The major objectives are to show that enhanced oxidative stress and inflammation contribute to the age-related major eye diseases. This review presents rationales for using a comprehensive mixture of micronutrients containing dietary and endogenous antioxidants, vitamin D3, and carotenoids such as lutein, zeaxanthin, astaxanthin, all B-vitamins, and minerals Zn and Se for simultaneously reducing oxidative and inflammatory damage. Since elevated levels of vascular endothelial growth factor (VEGF) are found in the wet ARMD and diabetic retinopathy, this mixture has ingredients, which reduce VEGF levels. Supplementation with this micronutrient mixture may delay the onset and progression of major eye diseases, and may improve the effectiveness of standard therapy.

Regulatory Effects of Quercetin on M1/M2 Macrophage Polarization and Oxidative/Antioxidative Balance

Macrophage polarization plays essential and diverse roles in most diseases, such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Homeostasis dysfunction in M1/M2 macrophage polarization causes pathological conditions and inflammation. Neuroinflammation is characterized by microglial activation and the concomitant production of pro-inflammatory cytokines, leading to numerous neurodegenerative diseases and psychiatric disorders. Decreased neuroinflammation can be obtained by using natural compounds, including flavonoids, which are known to ameliorate inflammatory responses. Among flavonoids, quercetin possesses multiple pharmacological applications and regulates several biological activities. In the present study, we found that quercetin effectively inhibited the expression of lipocalin-2 in both macrophages and microglial cells stimulated by lipopolysaccharides (LPS). The production of nitric oxide (NO) and expression levels of the pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, were also attenuated by quercetin treatment. Our results also showed that quercetin significantly reduced the expression levels of the M1 markers, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, in the macrophages and microglia. The M1 polarization-associated chemokines, C–C motif chemokine ligand (CCL)-2 and C-X-C motif chemokine ligand (CXCL)-10, were also effectively reduced by the quercetin treatment. In addition, quercetin markedly reduced the production of various reactive oxygen species (ROS) in the microglia. The microglial phagocytic ability induced by the LPS was also effectively reduced by the quercetin treatment. Importantly, the quercetin increased the expression levels of the M2 marker, IL-10, and the endogenous antioxidants, heme oxygenase (HO)-1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1). The enhancement of the M2 markers and endogenous antioxidants by quercetin was activated by the AMP-activated protein kinase (AMPK) and Akt signaling pathways. Together, our study reported that the quercetin inhibited the effects of M1 polarization, including neuroinflammatory responses, ROS production, and phagocytosis. Moreover, the quercetin enhanced the M2 macrophage polarization and endogenous antioxidant expression in both macrophages and microglia. Our findings provide valuable information that quercetin may act as a potential drug for the treatment of diseases related to inflammatory disorders in the central nervous system.

Metabolic and Redox Biomarkers in Skeletal Muscle Underlie Physiological Adaptations of Two Estivating Anuran Species in a South American Semi-arid Environment

The upregulation of endogenous antioxidants (i.e., preparation for oxidative stress, POS) is part of the biochemical responses underlying the adaptation of animals to adverse environments. Despite the phylogenetic diversity of animals in which POS has been described, most studies focus on animals under controlled laboratory conditions. To address this limitation, we have recently assessed the redox metabolism in the skeletal muscle of Proceratophrys cristiceps estivating under natural settings in the Caatinga. Here, we analyzed biochemical biomarkers in the muscle of another Caatinga species, Pleurodema diplolister, during the rainy (active) and dry (estivating frogs) seasons. We aimed to determine whether P. diplolister enhances its antioxidants during estivation under field conditions and to identify any effect of species on the biochemical responses of P. diplolister and P. cristiceps associated with estivation. To do so, we measured the activities of representative enzymes of intermediary metabolism and antioxidant systems, as well as glutathione and protein carbonyl levels, in the skeletal muscle of P. diplolister. Our findings revealed the suppression of oxidative metabolism and activation of antioxidant enzymes in estivating P. diplolister compared with active specimens. No changes in oxidative damage to proteins were observed and estivating P. diplolister had lower levels of disulfide glutathione (GSSG) and disulfide-to-total glutathione ratio (GSSG/tGSH) than those observed in active individuals. When data for P. diplolister and P. cristiceps were assembled and analyzed, significant effects of species were detected on the activities of metabolic enzymes (citrate synthase, isocitric dehydrogenase, malic enzyme, and creatine kinase) and antioxidant enzymes (catalase, glutathione peroxidase and glutathione transferase), as well as on GSSG/tGSH ratio. Such effects might underlie the physiological and behavioral differences between these two species that share the same microhabitat and survival strategy (i.e., to estivate) during the dry season. Despite some peculiarities, which reflect the physiological diversity of the mechanisms associated with estivation in the Brazilian Caatinga, both P. diplolister and P. cristiceps seem to balance the suppression of oxidative pathways, the maintenance of the capacity of oxygen-independent pathways, and the activation of endogenous antioxidants to preserve muscle function and be ready to resume activity whenever the unpredictable rainy period arrives.

Heptapeptide Isolated from Isochrysiszhanjiangensis Exhibited Anti-Photoaging Potential via MAPK/AP-1/MMP Pathway and Anti-Apoptosis in UVB-Irradiated HaCaT Cells

Marine microalgae can be used as sustainable protein sources in many fields with positive effects on human and animal health. DAPTMGY is a heptapeptide isolated from Isochrysis zhanjiangensis which is a microalga. In this study, we evaluated its anti-photoaging properties and mechanism of action in human immortalized keratinocytes cells (HaCaT). The results showed that DAPTMGY scavenged reactive oxygen species (ROS) and increase the level of endogenous antioxidants. In addition, through the exploration of its mechanism, it was determined that DAPIMGY exerted anti-photoaging effects. Specifically, the heptapeptide inhibits UVB-induced apoptosis through down-regulation of p53, caspase-8, caspase-3 and Bax and up-regulation of Bcl-2. Thus, DAPTMGY, isolated from I. zhanjiangensis, exhibits protective effects against UVB-induced damage.

MUCUNA SEED POWDER SUPPLEMENTATION VALUE ON BROILER CHICKENS PERFORMANCE, ANTIOXIDANT ENZYMES, MEAT CHOLESTEROL, PEROXIDATION, AND SERUM METABOLITES

This study examined the effect of Mucuna seed powder (MSP) supplementation on performance, meat, and health status of broiler chickens. A total of 300 broiler chicks were randomly allocated into 5 treatments with 6 replicates of 10 birds each, as follows: Diet 1 (control), Diet 2 (diet supplemented with 1.1% oxytetracycline, OXYT), Diet 3 (diet with 0.5% MSP), Diet 4 (diet with 1.0% MSP) and Diet 5 (diet with 1.5% MSP). The dietary MSP supplementation significantly (P<0.05) increased the daily body weight gain of the broiler chickens, compared to those fed the control diet at the starter phase and overall (1-42 days) period of the feeding trial. No significant differences were observed in the measured aspartate aminotransferase (AST), creatinine, and alanine aminotransferase (ALT) among the treatments. The broiler chicken fed diets supplemented with MSP had higher (P<0.05) total serum glutathione peroxidase and superoxide dismutase compared to those fed the control diet. The concentration of muscle cholesterol and lipid peroxidation reduced significantly (P<0.05) in the birds fed MSP supplemented diets compared to those fed the control diet. In conclusion, this study has shown that MSP can be used up to 1.5% as a potential phytogenic feed supplement in a broiler diet to enhance the growth performance, maintain the carcass traits, boost endogenous antioxidants and reduce meat cholesterol level and lipid oxidation.

Curcumin Attenuates Hepato-, and Nephrotoxicity Induced by Cypermethrin Through Inhibition of Oxidative Stress in Male Albino Rabbits

The reactive oxygen species (ROS) have been involved in the toxicity of several pesticides. This study was aimed to induce oxidative stress in rabbit’s liver and kidney by cypermethrin (CYP), a type II pyrethroid pesticide and to evaluate the protective effect of Curcumin (CMN). Numerous plant moieties are identified to exhibit protective potential by neutralizing the oxidative stress. In this study we evaluated the protective role of powdered dried rhizome of curcuma longa L. (CMN) against CYP-induced liver and renal toxicity. For this purpose, all the rabbits were divided in 4 groups, each containing 5 rabbits. The 1st group considered as control while 2nd, 3rd and 4th group were treated with CYP (25mg/kg), CMN (50 mg/kg) alone and CYP (25 mg/kg) in combination with CMN (50 mg/kg), respectively. Biochemical markers were investigated in serum while antioxidant potential and histopathological analysis was performed in liver and kidney tissues. CYP administration resulted in significant reduction of antioxidant protein and enzymes (GSH, GST, catalase, SOD and GPx). Moreover, remarkable variations were observed in biochemical markers (urea, creatinine, AST, ALT, ALP and bilirubin) as well as in histology of kidney and liver in CYP-treated rabbits. The administration of CMN in combination with CYP significantly restored the level of endogenous antioxidants. Furthermore, the normal level of serum biochemical markers was observed with normal histology of liver and kidney in rabbits treated with CMN. Similarly, CMN alleviated the harmful effects of CYP on lipid profiles, hematological parameters and body weight of rabbits.

Cellular Defensive Mechanisms of Tea Polyphenols: Structure-Activity Relationship

Tea is particularly rich in polyphenols, including catechins and theaflavins, thearubigins, flavonols, and phenolic acids, which are believed to contribute to the health benefits of tea. The health-promoting effects of tea polyphenols are believed to be related to their cellular defensive properties. This review is intended to briefly summarize the relationship between the chemical structures of tea polyphenols and their biological activities. Tea polyphenols appear as direct antioxidants by scavenging reactive oxygen/nitrogen species; chelating transition metals; and inhibiting lipid, protein, and DNA oxidations. They also act directly by suppressing “pro-oxidant” enzymes, inducing endogenous antioxidants, and cooperating with vitamins. Moreover, tea polyphenols regulate cellular signaling transduction pathways, importantly contributing to the prevention of chronic diseases and the promotion of physiological functions. Apparently, the features in the chemical structures of tea polyphenols are closely associated with their antioxidant potentials.

Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.

The effects of quercetin on nicotine-induced reward effects in mice

Objectives Tobacco smoking remains the primary cause of preventable mortality and morbidity in the world. The complexity of the nicotine dependency process included the withdrawal effect that triggers recurrence being the main problem. Quercetin, known as an antioxidant, binds free radicals and modulates endogenous antioxidants through Nrf2 activations is expected as a potential agent to reduce the risk of nicotine dependence. This research aims to evaluate quercetin’s effects on reducing the risk of nicotine addiction. Methods Conditioned Place Preference (CPP) with a biased design was used to evaluate nicotine’s reward effects in male Balb/C mice. Preconditioning test was performed on day 1; conditioning test was done twice daily on day 2–4 by administering quercetin (i.p.) 50 mg/kg along with nicotine (s.c.) 0.5 mg/kg or Cigarette Smoke Extract (CSE) (s.c.) contained nicotine 0.5 mg/kg; and postconditioning test was performed on day 5 continue with extinction test on day 6, 8, 10, 12, and reinstatement test on day 13. The duration spent in each compartment was recorded and analyzed. Results Nicotine 0.5 mg/kg and CSE 0.5 mg/kg significantly induced reward effects (p<0.05). There was no decrease of reward effect during the extinction-reinstatement stage of the postconditioning phase (p>0.05), while quercetin 50 mg/kg both induced along with nicotine or CSE was able to inhibit the reward effect of nicotine (p>0.05). Conclusions Quercetin reduced the risk of nicotine dependence and has a potential effect to use as a therapy for nicotine dependence, especially as a preventive agent.