Antioxidant Properties of Trianthema Portulacastrum and Protection Against Ionizing Radiation-Induced Liver Damage Ex vivo.

Antioxidants in fruits and vegetables protect cells against radiation induced damage. Trianthema portulacastrum is used as vegetables from ancient time. The effects of T. Portulacastrum ethanolic extracts against γ-radiation induced liver tissue damage ex vivo were evaluated in this study. Antioxidant phytochemicals present in T. Portulacastrum includes flavonoids [3.3 ± 0.15 to 10 ± 0.16 mg catethin equivalent (CE)/g fresh weight (fw)], ascorbic acid (0.15 ± 0.03 to 0.21 ± 0.03 mg/g fw), glutathione s-transferase (GST) (1.57 ± 0.06 to 3.59 ± 0.05 nmole/mg fw/min), superoxide dismutase (SOD) (1.6 ± 0.03 to 1.79 ± 0.04 U/min), peroxidase (3.26 ± 0.18 to 6.38 ± 0.03 U/g fw) and catalase (0.51 ± 0.03 to 2.84 ± 0.15 mg H2O2 decomposed/g fw/min). Total phenolic content varied from 122.9 ± 8.7 to 302.8 ± 15.7 mg gallic acid equivalent/g extract, and flavonoid content varied from 316.7 ± 33.3 to 800.7 ± 28.9 CE mg/g extract. The IC50 value of Nitric oxide (NO•) scavenging activity of extracts varies from 208.7 to 387.4 µg/ ml. Pre-treatment with the T. portulacastrum extracts mitigated the 4-Gy gamma(γ) radiation-induced oxidative stress related parameters in hepatic tissue such as TBARS, catalase, nitrite, Glutathione reductase (GR), SOD and GST in dose dependent manner. The ethanolic extract of the stem from T. Portulacastrum demonstrated highest protection in comparison to leaf and whole plant extracts. This study demonstrated the hepatoprotective efficacy of T. portulacastrum extracts against γ-radiation in ex-vivo condition was possibly due to its potential antioxidant properties of phenolic and flavonoids present in extracts.

Modulating Insulin Aggregation with Charge Variable Cholic Acid-Derived Polymers.

To understand the effect of cholic acid (CA)-based charge variable polymeric architectures on modulating the insulin aggregation process, herein, we have designed side-chain cholate-containing charge variable polymers. Three different types of copolymers from 2-(methacryloyloxy)ethyl cholate with anionic or cationic or neutral units have been synthesized by reversible addition-fragmentation chain transfer polymerization. The effects of these copolymers on the insulin fibrillation process was studied by multiple biophysical approaches including different types of spectroscopic and microscopic analyses. Interestingly, the CA-based cationic polymer (CP-10) was observed to inhibit the insulin fibrillation process in a dose-dependent manner and to act as an effective anti-amyloidogenic agent. Corresponding anionic (AP-10) and neutral (NP-10) copolymers with cholate pendants remained insignificant in controlling the aggregation process. Tyrosine fluorescence assays and Nile red fluorescence measurements demonstrate the role of hydrophobic interaction to explain the inhibitory potencies of CP-10. Furthermore, circular dichroism spectroscopic measurements were carried out to explore the secondary structural changes of insulin fibrils in the presence of cationic polymers with and without cholate moieties. Isothermal titration calorimetry measurements revealed the involvement of electrostatic polar interaction between the CA-based cationic polymer and insulin at different stages of fibrillation. Overall, this work demonstrates the efficacy of the CA-based cationic polymer in controlling the insulin aggregation process and provides a novel dimension to the studies on protein aggregation.

Clinical Characteristics of Paediatric Hyperinflammatory Syndrome in the Era of Corona Virus Disease 2019 (COVID-19).

The pandemic of COVID-19 initially appeared to cause only a mild illness in children. However, it is now apparent that a small percentage of children can develop a hyperinflammatory syndrome labeled as Pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2 (PIMS-TS) with a phenotype resembling Kawasaki disease (KD) ('Kawa-COVID-19'). Features of this newly recognized condition may include fever, hypotension, severe abdominal pain and cardiac dysfunction, evidence of inflammation, and single or multi organ dysfunction in the absence of other known infections. Children emerge to have mild symptoms compared to adults, perhaps due to reduced expression of the angiotensin converting enzyme (ACE)-2 receptor (the target of SARS-CoV-2) gene, trained innate immunity, and a young and fit immune system. Some of these children may share features of Kawasaki disease, toxic shock syndrome or cytokine storm syndrome. They can deteriorate rapidly and may need intensive care support as well. The PCR test is more often negative although most of the children have antibodies to SARS-CoV-2. Although the pathogenesis is not clearly known, immune-mediated injury has been implicated.

The Pathophysiology, Diagnosis and Treatment of Corona Virus Disease 2019 (COVID-19).

Since the beginning of this century, beta coronaviruses (CoV) have caused three zoonotic outbreaks. However, little is currently known about the biology of the newly emerged SARS-CoV-2 in late 2019. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, acute respiratory distress syndrome, acute cardiac injury and septic shock. The genome of SARS-CoV-2 encodes polyproteins, four structural proteins and six accessory proteins. SARS-CoV-2 tends to utilize Angiotensin-converting enzyme 2 (ACE2) of various mammals. The imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang(1-7)/Mas receptor pathway in the renin-angiotensin system leads to multi-system inflammation. The early symptoms of COVID-19 pneumonia are low to midgrade fever, dry cough and fatigue. Vigilant screening is important. The diagnosis of COVID-19 should be based on imaging findings along with epidemiological history and nucleic acid detection. Isolation and quarantine of suspected cases is recommended. Management is primarily supportive, with newer antiviral drugs/vaccines under investigation.

Grape extract protects against ionizing radiation-induced membrane alterations in Red Blood Cells.

Ionizing radiation causes damage to biomolecules in living cells through oxidative stress by excessive generation of reactive oxygen species (ROS) from radiolysis of body water. Blood and its components including the cells are exposed to a significant dose of radiation during irradiation. Grapes (Vitis vinifera L.) contain several bioactive phytochemicals and are rich source of antioxidants. Therefore, we hypothesized that the grape extracts would offer protection against the ionizing radiation-induced damage of the red blood cells (RBCs). To test our hypothesis, in the current study we investigated the radio-protective actions of extract of four different grape (Vitis vinifera) cultivars, namely Flame seedless (Black grapes), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Sonaka, Green) against the g-irradiation-induced oxidative stress leading to the structural alteration in the RBC membrane in vitro. Freshly drawn blood samples from healthy volunteers itself or mixed with grape extracts from seed, skin or pulp of each cultivar were irradiated at 4 Gy after one hour of treatment. -irradiation for one hour did not change the hematological parameters. The average osmotic fragility (H50) and the maximum rate of hemolysis (dH/dC)max increased after the -irradiation. The confocal microscopic and atomic force microscopic (AFM) studies showed that irradiation induced transformation of RBC from biconcave cells to echinocytes, altered their surface roughness and the vertical distance. The grape extracts did not alter the viability of human erythrocytes. Our results suggested that the grape extract pretreatment ameliorated the ionizing radiation-induced alterations at a dose of 4 Gy in human erythrocytes in vitro. Moreover, protection offered by the seed extract was significantly better than that that of skin or pulp of the same cultivar. Furthermore, the protective action of grape extract depends on its source (seed, skin or pulp) as well on cultivars.

Scavenging and antioxidant properties of different grape cultivars against ionizing radiation-induced liver damage ex vivo.

Ionizing radiation (IR) has become an integral part of the modern medicine--both for diagnosis as well as therapy. However, normal tissues or even distant cells also suffer IR-induced free radical insult. It may be more damaging in longer term than direct radiation exposure. Antioxidants provide protection against IR-induced damage. Grapes are the richest source of antioxidants. Here, we assessed the scavenging properties of four grape (Vitis vinifera) cultivars, namely Flame seedless (Black), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Green), and also evaluated their protective action against γ-radiation-induced oxidative stress in liver tissue ex vivo. The scavenging abilities of grape seeds [2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 0.008 ± 0.001 mg/mL), hydrogen peroxide (IC50 = 0.49 to 0.8 mg/mL), hydroxyl radicals (IC50 = 0.08 ± 0.008 mg/mL), and nitric oxide (IC50 = 0.8 ± 0.08 mg/mL)] were higher than that of skin or pulp. Gamma (γ) radiation exposure to sliced liver tissues ex vivo from goat, @ 6 Gy significantly (P < 0.001) decreased reduced glutathione (GSH) content by 21.2% and also activities of catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST) by 49.5, 66.0, 70.3, 73.6%, respectively. However, it increased thiobarbituric acid reactive substances (TBARS) by 2.04-fold and nitric oxide level by 48.6% compared to untreated group. Further increase in doses (10 or 16 Gy) of γ-radiation correspondingly decreased GSH content and enzyme activities, and increased TBARS and nitric oxide levels. Grape extract treatment prior to ionizing radiation exposure ameliorated theses effects at varying extent. The seed extracts exhibited strong antioxidant potential compared to skin or pulp extracts of different grape cultivars against oxidative damage by ionizing radiation (6 Gy, 10 Gy and 16 Gy) in sliced liver tissues ex vivo. Grape extracts at higher concentration (10 mg extract/g liver tissue) showed stronger antioxidant potential against lower dose (6 Gy) of ionizing radiation. Our results suggest that grape extracts could serve as a potential source of natural antioxidant against lower doses of IR-induced oxidative stress in liver extracts ex vivo.

Black tea extract protects against -radiation-induced membrane damage of human erythrocytes.

The membrane integrity of circulating red blood cells (RBCs) is compromised by the deleterious actions of -radiation in humans. Tea is the most widely consumed popular, inexpensive and non-toxic beverage rich in antioxidants. Here, we explored the radioprotective actions of black tea against the -radiation-induced membrane permeability of human erythrocytes. The phytochemical analysis of tea revealed the total polyphenol content to be 114.89±6.03 mg gallic acid equivalent/g dry wt. and flavonoid content, 34±0.11 mg catechin equivalent/g dry wt. of the extractable solid in the commercially available tea bags. Tea extracts showed potential scavenging of H2O2 and NO, appreciable extent of total antioxidant capacity and effective anti-hemolytic action. Tea extracts (15 µg/mL) significantly ameliorated the -radiation-induced increase of the levels of thiobarbituric acid-reactive substances (TBARS, an index of lipid peroxidation) in the RBC membrane ghosts. Stored blood showed higher levels of K+ ion as compared to the normal blood which was elevated by -radiation. Membrane ATPase was inhibited by the exposure to -radiation. Treatment of RBCs with the tea extracts (15 µg/ml) prior to the exposure of -radiation significantly mitigated these changes in the erythrocyte membranes caused by the lower dose of radiation (4 Gy) as compared to that induced by the higher dose of -radiation.

Grapevine fruit extract protects against radiation-induced oxidative stress and apoptosis in human lymphocyte.

Ionizing radiation (IR) causes oxidative stress through overwhelming generation of reactive oxygen species (ROS) in the living cells leading the oxidative damage further to biomolecules. Grapevine (Vitis vinifera L.) posses several bioactive phytochemicals and is the richest source of antioxidants. In this study, we investigated V. vinifera for its phytochemical content, enzymes profile and, ROS- and oxidant-scavenging activities. We have also studied the fruit extract of four different grapevine viz., Thompson seedless, Flame seedless, Kishmish chorni and Red globe for their radioprotective actions in human lymphocytes. The activities of ascorbic acid oxidase and catalase significantly (P < 0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. Pretreatment with grape extracts attenuated the oxidative stress induced by 4 Gy γ-radiation in human lymphocytes in vitro. Further, γ-radiation-induced increase in caspase 3/7 activity was significantly attenuated by grape extracts. These results suggest that grape extract serve as a potential source of natural antioxidants against the IR-induced oxidative stress and also inhibit apoptosis. Furthermore, the protective action of grape depends on the source of extract (seed, skin or pulp) and type of the cultivars.

Free Radical Scavenging Properties of Skin and Pulp Extracts of Different Grape Cultivars In Vitro and Attenuation of H2O2-Induced Oxidative Stress in Liver Tissue Ex Vivo.

Grapes are the richest source of antioxidants due to the presence of potent bioactive phytochemicals. In this study, the phytochemical contents, scavenging activities and protective role against H2O2-induced oxidative stress in liver tissue ex vivo of four grape (Vitis vinifera) cultivars extracts, namely Flame seedless (black), Kishmish chorni (black with reddish brown), Red globe (red) and Thompson seedless mutant (green), were evaluated. The total phenolics and flavonoids content in pulp or skin fractions of different grape cultivars were in the range of 47.6-310 mg gallic acid equivalent/g fresh weight (fw), and 46.6-733.3 µg catechin equivalent/g fw respectively. The scavenging activities in skin of different grape varieties against 2,2-diphenyl-1-picrylhydrazyl (44-58 %), hydrogen peroxide (15.3-18.6 %), and hydroxyl radicals (50-85 %), were higher than pulp of the corresponding cultivars. These scavenging activities of grape extracts were found to be significantly (p < 0.01) correlated with the levels of total phenols, flavonoids and ascorbic acid. Liver tissues from goat treated with H2O2 (500 µM) showed significantly decreased GSH content by 42.9 % and activities of catalase by 50 % and glutathione reductase by 66.6 %; while increased thiobarbituric acid reactive substances and nitric oxide level by 2.53- and 0.86-fold, respectively, and activity of glutathione S-transferase by 0.96-fold. Grape skin extracts showed the stronger protective activity against H2O2-induced oxidative stress in liver tissue ex vivo, than its pulp of any cultivar; and the Flame seedless (black) cultivar showed the highest potential. In conclusion, our study suggested that the higher antioxidant potential, phytochemical contents and significant scavenging capacities in pulp and skin of grape extracts showed the protective action of grape extracts against H2O2-induced oxidative stress in liver tissue ex vivo.

Challenges of ionizing radiation in tumor treatment and role of angiogenesis.

Ionizing radiation is a non-specific, but most widely used therapeutic method for cancer treatment. However, a minor fraction of tumor cell population manages to survive after radiation. Radiation efficacy depends on adequate oxygen supply. Rapid growing tumors cause hypoxia that upregulates many pro-survival pathways. At clinical doses, radiation activates inflammatory pathways and causes oxidative stress that plays a positive role during angiogenesis. Selective targeting of signaling mechanisms may radiosensitize tumors.

Antioxidant potential of different grape cultivars against Fenton-like reagent-induced liver damage ex-vivo.

The phytochemicals present in the grapes are responsible for nutraceutical and health benfits due to their antioxidant properties. These phytochemicals, however, vary greatly among different cultivars. In this study, we evaluated the antioxidant potential and protective role of four different Indian grape (Vitis vinifera) cultivars extracts, namely Flame seedless (Black grapes), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Sonaka, Green) against the Fenton-like reagent (200 µmole H2O2, 2 mmole ascorbate, 25 µmole FeSO4)-induced liver damage. Non-enzymatic antioxidants, such as glutathione (GSH) levels and activities of antioxidant enzymes, such as glutathione S-transferase (GST) and superoxide dismutase (SOD), as well as total antioxidant capacity (TAC) were highest in the grape seed, followed by skin and pulp. Among edible parts of different cultivars, skin of Flame seedless (Black) cultivar showed highest antioxidant potential, while the Thompson seedless the least potential. These antioxidants were found to be significantly (P < 0.01) correlated with the levels of total phenol, flavonoids and ascorbic acid. Fenton-like reagent treatment significantly (P < 0.001) decreased GSH content by 39.1% and activities of catalase (CAT) by 43.2% and glutathione reductase (GR) by 60%, while increasing thiobarbituric acid reactive substances (TBARS) and nitric oxide levels by 2.13-fold and 0.64-fold, respectively and GST activity by 0.81-fold. Pre-treatment with grape seed extracts showed the best hepatoprotective action against Fenton-like reagent-induced damage, followed by the extracts of skin and pulp of any cultivar. Thus, our study showed the significant amounts of antioxidants were in grape seed, followed by its skin and pulp, which varied among the cultivars and was associated with the protective action of grape extracts against Fenton-like reagent-induced liver damage ex-vivo.

Role of nitric oxide, angiogenic growth factors and biochemical analysis in preeclampsia.

Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal mortality and morbidity globally. Angiogenic growth factors, including vascular endothelial growth factor (VEGF) and placental growth factor (P1GF) are involved in the generation of new blood vessels required for placental development and physiological functions, while nitric oxide (NO) acts as vasodilator and also plays a role in angiogenesis. The objective of this study was to evaluate the role of NO, angiogenic growth factors (VEGF and PIGF) and other biochemical parameters in the development of preeclampsia among pregnant mothers. A complete clinical history, including anthropometric measurements and biochemical investigations, including renal function tests, liver function tests and lipid profile were performed among twenty preeclampsia patients aged 19 to 32 yrs. Results were compared with age-matched normotensive pregnant mothers. The body weight, body mass index (BMI), blood pressure, concentrations of urea, uric acid and triglyceride and activities of transaminase enzymes (aspartate transaminase, AST and alanine transaminase, ALT) in serum were significantly higher (p < 0.05) than normotensive subjects. Serum concentrations of VEGF, P1GF and NO were significantly decreased (p < 0.005) in preeclamptic patients. NO was found negatively correlated with body weight (r = -0.369, p < 0.05), systolic blood pressure (r = -0.822, p < 0.005), diastolic blood pressure (r = -0.714, p < 0.005) and was positively correlated with VEGF (r = 0.464, p < 0.005) and P1GF (r = 0.546, p < 0.005). VEGF and P1GF showed significant (p < 0.005) negative correlation with systolic and diastolic blood pressure and PIGF was significantly correlated with triglyceride (r = -0.379). However, no significant correlation was observed between the VEGF and P1GF. In conclusion, the results indicated that body weight, triglyceride, angiogenic growth factors and NO might associate with preeclampsia development.

Biochemical and immunological basis of silymarin effect, a milk thistle (Silybum marianum) against ethanol-induced oxidative damage.

Ethanol metabolism induces generation of excessive amount of reactive oxygen species (ROS) which results in immune dysfunction. We examined the efficacy of silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and vascular function in mice blood. Effectiveness of silymarin was compared with potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male BALB/c mice (20-30 g) were divided into the four groups of six each. One group were fed with ethanol (1.6 g/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250 mg/kg body weight) per day for 12 weeks. The control group was fed with isocaloric glucose solution instead of ethanol. Ethanol exposure significantly increased thiobarbituric acid reactive substance (TBARS) and nitrite levels besides glutathione-S-transferase (GST) activity, and significantly decreased reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in whole blood hemolyzate, while silymarin treatment significantly normalized these altered parameters. Silymarin significantly prevented ethanol-induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)-α, γ interferon (IFN-γ), vascular endothelial growth factor (VEGF)-A, and transforming growth factor (TGF)-ß1, as well as decreased IL-4 activity in mice blood. These results were comparable with the activity of ascorbic acid.

Effects of long term ethanol consumption mediated oxidative stress on neovessel generation in liver.

Angiogenesis, the growth of new blood vessels, is essential during tissue repair. Though most molecular mechanisms of angiogenesis are common to the liver and other organs, there was no report available whether alcoholic liver disease also causes angiogenesis. In this study, we examined the effects of long term ethanol (1.6 g/kg body weight/day) consumption on angiogenic responses in the liver of male Wistar strain albino rats (16-18 weeks old, weighing 200-220 g) up to 36 weeks. Chronic ethanol consumption was associated with not only elevated oxidative stress, and altered cytokines expression, but also developed large von Willebrand factor, fibrosis and activation of matrix metalloproteinases. Moreover, vascular endothelial growth factor-receptor 2 (VEGF-R2, fetal liver kinase 1: Flk-1/KDR) expression and neovessel generation in the rat liver were noted after 36 weeks of ethanol consumption. Thus our study provides novel evidence that long-term ethanol consumption is associated with angiogenesis through delicate and coordinated action of a variety of mediators.

Dietary grapes (Vitis vinifera) feeding attenuates ethanol-induced oxidative stress in blood and modulates immune functions in mice.

Ethanol metabolism is known to induce overwhelming production of reactive oxygen species (ROS) and also to cause associated immune dysfunction. Several interventional agents of plant origin, in particular fruits and vegetables have been used to counteract these alterations induced by ethanol. In this study, we investigated the efficacy of dietary feeding of skin and flesh of grapes (Vitis vinifera L.) on the alterations in immune and vascular functions in mice with liver abnormalities induced by chronic ethanol consumption. Results revealed that feeding of both grape skin and flesh (2.5 g/kg body wt/day) effectively attenuated the oxidative stress and alterations in immune function and angiogenesis induced by chronic ethanol consumption (1.6 g/kg body wt/day for 12 weeks) in mice. The antioxidant actions of the grape skin and flesh as observed in this study might be attributed to the polyphenols present in the grapes.

Effects of long-term ethanol consumption on adhesion molecules in liver.

Adhesion molecules play an important role in the pathogenesis of several diseases. In this study, expression of adhesion molecules was examined in the setting of chronic alcohol induced liver damage of male albino Wistar strain rats (16-18 weeks-old, 200-220 g) in a time dependent manner. Decreased protein level and increased activities of liver marker enzymes in response to the chronic ethanol (1.6 g ethanol/kg body weight/day) exposure, indicated that these animals suffered from liver damage in a time-dependent manner. Flow cytometric analysis revealed that chronic ethanol treatment induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 expression in liver tissues of rats with duration of ethanol exposure. The results suggest that the adhesion molecules may be associated with the initiation of hepatic injury during alcohol intoxication.