Free Radical Scavenging Agents Research Articles

The case for neuregulin-1 as a clinical treatment for stroke.

Ischemic stroke is the leading cause of serious long-term disability and the 5th leading cause of death in the United States. Revascularization of the occluded cerebral artery, either by thrombolysis or endovascular thrombectomy, is the only effective, clinically-approved stroke therapy. Several potentially neuroprotective agents, including glutamate antagonists, anti-inflammatory compounds and free radical scavenging agents were shown to be effective neuroprotectants in preclinical animal models of brain ischemia. However, these compounds did not demonstrate efficacy in clinical trials with human patients following stroke. Proposed reasons for the translational failure include an insufficient understanding on the cellular and molecular pathophysiology of ischemic stroke, lack of alignment between preclinical and clinical studies and inappropriate design of clinical trials based on the preclinical findings. Therefore, novel neuroprotective treatments must be developed based on a clearer understanding of the complex spatiotemporal mechanisms of ischemic stroke and with proper clinical trial design based on the preclinical findings from specific animal models of stroke. We and others have demonstrated the clinical potential for neuregulin-1 (NRG-1) in preclinical stroke studies. NRG-1 significantly reduced ischemia-induced neuronal death, neuroinflammation and oxidative stress in rodent stroke models with a therapeutic window of >13 h. Clinically, NRG-1 was shown to be safe in human patients and improved cardiac function in multisite phase II studies for heart failure. This review summarizes previous stroke clinical candidates and provides evidence that NRG-1 represents a novel, safe, neuroprotective strategy that has potential therapeutic value in treating individuals after acute ischemic stroke.

Development and Validation of Derivatization Method for Simultaneous Quantitation of Asteracantha longifolia (L.) Nees Phytoconstituents by Liquid Chromatography–Electrospray Ionization–Mass Spectrometry/Mass Spectrometry

ABSTRACT Background: Betulin, lupeol, stigmasterol, and β-sitosterol are the active phytoconstituents accountable for the practical application of Asteracantha longifolia (L.) Nees in ayurvedic treatments as antitumor, hypoglycemic, aphrodisiac, antibacterial, free radical scavenging, lipid peroxidation, and hepatoprotective agent. As an essential medicinal plant in modern and traditional medicine, regularly checking raw material’s quality attributes and quantifying the phytoconstituents is indispensable. Aim: The aim of this study was to optimize derivatization conditions of these four essential phytoconstituents with p-toluenesulfonyl isocyanate (PTSI) reagent and the development of a liquid chromatography–electrospray ionization (ESI)–mass spectrometry (MS)/MS method that aids in the simultaneous detection of these four phytoconstituents. Objective: Thus, derivatization enhances sensitivity for detection in the negative mode with an electron spray ionization source and tandem mass spectroscopy. Further, the sensitive and rapid analytical method for simultaneous quantitation of betulin, lupeol, stigmasterol, and β-sitosterol is subsequently validated in line with the guidelines by ICH and used to quantify the phytoconstituents in two over-the-counter herbal formulations and one plant extract isolated at laboratory scale under batch analysis. Materials and Methods: PTSI reagent of purity <98% procured from TCI and other chromatography reagents of MS grade were utilized in the optimization of an analytical method. Results: The developed LC-ESI-MS/MS-based method demonstrated specificity for the targeted phytoconstituents, with LOD and LOQ values of < 0.13 ng/mL and 0.4 ng/mL, respectively. Linearity was established with a correlation coefficient ≥ 0.998 over a concentration range of 0.2 ng/mL to 6 ng/mL. Precision, expressed as %RSD for peak response, was ≤ 5%. The method showed satisfactory recovery for betulin (98.5%-108.3%), lupeol (95.0%-109.3%), stigmasterol (101.9%-117.0%), and β-sitosterol (99.1%-116.2%). Conclusion: The reagent PTSI reacts rapidly and forms stable derivatives. The derivatization of active phytoconstituents betulin, lupeol, stigmasterol, and β-sitosterol has enhanced the detection sensitivity of the analytical method.

An Analysis of Antioxidant Therapies for COVID‐19

AbstractOxidative stress and inflammation are observed in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). As oxidative stress is due to free radicals, free radical scavenging agents, such as vitamin C, are used in the hope of mitigating the severity of COVID‐19. In this paper an analytical model of free radical encounters within a cell is derived. It computes the effectiveness of free radical scavenging and the subsequent reduction in oxidative damage due to therapeutic intervention of exogenous antioxidants. Various publications make claims of success, albeit modest, treating critically ill COVID‐19 patients with high doses of vitamin C. The findings cast doubt on these claims and challenge the notion that any benefits attributed to vitamin C are due to free radical scavenging.

Coaxial 3D printing of hierarchical structured hydrogel scaffolds for on-demand repair of spinal cord injury.

After spinal cord injury (SCI), endogenous neural stem cells (NSCs) near the damaged site are activated, but few NSCs migrate to the injury epicenter and differentiate into neurons because of the harsh microenvironment. It has demonstrated that implantation of hydrogel scaffold loaded with multiple cues can enhance the function of endogenous NSCs. However, programming different cues on request remains a great challenge. Herein, a time-programmed linear hierarchical structure scaffold is developed for spinal cord injury recovery. The scaffold is obtained through coaxial 3D printing by encapsulating a dual-network hydrogel (composed of hyaluronic acid derivatives and N-cadherin modified sodium alginate, inner layer) into a temperature responsive gelatin/cellulose nanofiber hydrogel (Gel/CNF, outer layer). The reactive species scavenger, metalloporphyrin, loaded in the outer layer is released rapidly by the degradation of Gel/CNF, inhibiting the initial oxidative stress at lesion site to protect endogenous NSCs; while the inner hydrogel with appropriate mechanical support, linear topology structure and bioactive cues facilitates the migration and neuronal differentiation of NSCs at the later stage of SCI treatment, thereby promoting motor functional restorations in SCI rats. This study offers an innovative strategy for fabrication of multifunctional nerve regeneration scaffold, which has potential for clinical treatment of SCI. STATEMENT OF SIGNIFICANCE: Two major challenges facing the recovery from spinal cord injury (SCI) are the low viability of endogenous neural stem cells (NSCs) within the damaged microenvironment, as well as the difficulty of neuronal regeneration at the injured site. To address these issues, a spinal cord-like coaxial scaffold was fabricated with free radical scavenging agent metalloporphyrin Mn (III) tetrakis (4-benzoic acid) porphyrin and chemokine N-cadherin. The scaffold was constructed by 3D bioprinting for time-programmed protection and modulation of NSCs to effectively repair SCI. This 3D coaxially bioprinted biomimetic construct enables multi-factor on-demand repair and may be a promising therapeutic strategy for SCI.

Fabrication of Highly Thermally Resistant and Self-Healing Polysiloxane Elastomers by Constructing Covalent and Reversible Networks.

The fabrication of self-healing elastomers with high thermal stability for use in extreme thermal conditions such as aerospace remains a major challenge. A strategy for preparing self-healing elastomers with stable covalent bonds and dynamic metal-ligand coordination interactions as crosslinking sites in polydimethylsiloxane (PDMS) is proposed. The added Fe (III) not only serves as the dynamic crosslinking point at room temperature which is crucial for self-healing performance, but also plays a role as free radical scavenging agent at high temperatures. The results show that the PDMS elastomers possessed an initial thermal degradation temperature over 380°C and a room temperature self-healing efficiency as high as 65.7%. Moreover, the char residue at 800°C of PDMS elastomer reaches 7.19% in nitrogen atmosphere, and up to 14.02% in air atmosphere by doping a small amount (i.e., 0.3 wt%) of Fe (III), which is remarkable for the self-healing elastomers that contain weak and dynamic bonds with relatively poor thermal stability. This study provides an insight into designing self-healing PDMS-based materials that can be targeted for use as high-temperature thermal protection coatings.

Free radical scavenging activity, pancreatic lipase and a-amylase inhibitory assessment of ethanolic leaf extract of Phyllanthus amarus

Oxidative stress is associated with the pathogenesis of diabetes and obesity. The key enzymes involved in the carbohydrate and lipid metabolisms are a-amylase and pancreatic lipase respectively. The phytochemicals present in medicinal plants are known to be potent free radical scavenging agents and great inhibitors of metabolizing enzymes. Phyllanthus amarus leaves have antioxidant, anti-diabetic, and anti-obesity properties. This research is aimed at elucidating the carbohydrate and lipid metabolism inhibitory activities of P. amarus leaves through in-vitro screening. The phytochemical screening revealed that P.amarus is having high phenolic, flavonoid, tannin, and saponin content. The total protein content of P.amarus showed 2.720±0.001 mg BSAE/g. Diphenyl-2-picrylhydrazyl (DPPH) assay showed 0.0001mg/mL, Nitric oxide assay revealed 0.452 mg/mL, Ferric Reducing Antioxidant Power (FRAP) assay showed a value of 0.132±0.010 mg RE/g, Total antioxidant capacity (TAC) indicated a value of 2.217±0.002 mg GAE/g and 2,2-azino-bis(3-ethylbenzotiazoline)-6-sulfonic acid (ABTS) inhibitory activity at the peak concentration (1.2 mg/mL) was 40.29%. The enzyme inhibitory assessment showed a decrease in a-amylase activity as the concentration increased while there was a slight decrease in a-lipase activity but a slight increase at 18.75 mg/mL.

Novel Hybrid Indole-Based Caffeic Acid Amide Derivatives as Potent Free Radical Scavenging Agents: Rational Design, Synthesis, Spectroscopic Characterization, In Silico and In Vitro Investigations

Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A multiple-step scheme of in vitro radical scavenging assays was carried out to evaluate the antioxidant activity of the synthesized compounds. The results of the DPPH assay demonstrated that the indole-based caffeic acid amides are more active free radical scavenging agents than their benzamide analogues. Compared to Trolox, a water-soluble analogue of vitamin E, compounds 3a, 3f, 3h, 3j, and 3m were found to have excellent DPPH radical scavenging activities with IC50 values of 95.81 ± 1.01, 136.8 ± 1.04, 86.77 ± 1.03, 50.98 ± 1.05, and 67.64 ± 1.02 µM. Three compounds out of five (3f, 3j, and 3m) showed a higher capacity to neutralize the radical cation ABTS•+ more than Trolox with IC50 values of 14.48 ± 0.68, 19.49 ± 0.54, and 14.92 ± 0.30 µM, respectively. Compound 3j presented the highest antioxidant activity with a FRAP value of 4774.37 ± 137.20 μM Trolox eq/mM sample. In a similar way to the FRAP assay, the best antioxidant activity against the peroxyl radicals was demonstrated by compound 3j (10,714.21 ± 817.76 μM Trolox eq/mM sample). Taken together, compound 3j was validated as a lead hybrid molecule that could be optimized to maximize its antioxidant potency for the treatment of oxidative stress-related diseases.

Copper oxide nanoparticles using Mentha spicata leaves as antibacterial, antibiofilm, free radical scavenging agent and efficient photocatalyst to degrade methylene blue dyes

In this findings, CuO NPs were made by an easy, eco-friendly, and economical approach using the leaf extract of M. spicata . The prepared Ms-CuO NPs exhibited characteristic absorbance peak at 320 nm with a band gap of 3.87 eV. XRD revealed the presence of crystalline particle with size of 11.28 nm as determined by the Scherrer equation. FTIR revealed the role of various functional molecules in the bio-reduction of copper salts to copper ions (Cu 2+ ). The spherical shaped particles with the mean size of 36 nm were visualized through TEM microscopic image. EDX analysis also confirmed the elemental signals of Cu (91.58%) and O (8.42%) respectively. The biosynthesized Ms-CuO NPs displayed a significant inhibition of Gram-positive Streptococcus pyogenes and Staphylococcus aureus at all tested concentrations. The inhibition size against S. pyogenes and S. aureus was 27.5 ± 0.5 mm and 26.2 ± 0.2 mm at 100 µg mL −1 respectively. On the other hand, the inhibition against K. pneumoniae and E. coli was 17.4 ± 0.6 mm and 18.2 ± 0.1 mm at 100 µg mL −1 respectively. Moreover, a significant inhibition of H 2 O 2 (84%) at 100 µg mL −1 demonstrates the free radical scavenging activity of Ms-CuO NPs. Furthermore, the Ms-CuO NPs have shown excellent degradation potential for industrial dyes i.e., Methylene blue (MB) and was noticed by the gradual decrease in the absorbance (at 460 nm) within 7 h of reaction. The percentage of MB dye degraded was 34% at 1 h which was substantially increased to 98% after 7 h. This study suggests that the Ms-CuO NPs may serve as a promising bactericidal, antibiofilm and antioxidant agent. Also, Ms-CuO NPs could be effectively used in the purification of water bodies contaminated with harmful industrial dyes to reduce toxicity. • M. spicata leaf extract based CuO NPs were synthesized and characterized. • Ms-CuO NPs have shown significant antibacterial and antibiofilm effects. • Ms-CuO NPs have shown H 2 O 2 radical scavenging activity. • Ms-CuO NPs efficiently degraded the methylene blue dye.

In vitro propagation of Ocimum sanctum L., Ocimum canum Sims., and Ocimum tenuiflorum L., and evaluation of antioxidant, MMP-9 down regulation of eugenol and camphor

• Eugenol and camphor could be suitable candidates for preventing diseases caused by oxidative stress and free radicals. • Eugenol and camphor are effective MMP-9 inhibitors under in vitro . • Cytokinins are most suitable for micropropagation. Medicinal plants have long been used as a source of drugs. Ocimum species contain a diverse range of distillate that are abundant in phenolics, as well as a variety of other organic ingredients such as phytoconstituents. The present study was undertaken to standardize the medium for shoot and callus induction using nodal and leaf explants of Ocimum sanctum, Ocimum canum and Ocimum tenuiflorum and to perform RAPD analysis for identification of somaclonal variants. To evaluate the free radical scavenging activity of eugenol and camphor and to test MMP-9 inhibition of eugenol and camphor using gelatin zymography. Zeatin (6.8 µM) was observed to be suitable for the induction of shoots among the cytokinins evaluated in Ocimum sanctum and Ocimum canum . BA (6.6 µM) was shown to be more effective for shoot induction in Ocimum tenuiflorum . Supplemented B5 medium with 2,4-D (6.7µM and 4.5 µM) and B5 medium supplemented with NAA (8.5 µM) were reported to be favorable for callus induction in Ocimum sanctum and Ocimum canum respectively. The polymorphism was discovered in in vitro produced plants of Ocimum sanctum, Ocimum canum , and Ocimum tenuiflorum using the primers OPK4 and OPK10. Antioxidant activity of eugenol and camphor has been evaluated using various in vitro antioxidant assays. This study clearly indicates that eugenol is a potent free radical scavenging agent when compared with camphor. Eugenol and camphor were used to alleviate inflammation caused by lipopolysaccharide-induced overexpression of matrix metalloproteinase-9. Both eugenol and camphor are effective MMP-9 inhibitors in vitro , according to the results of this investigation. RT-PCR analysis clearly indicates the down regulation of over expressed MMP-9.

Aluminum oxide and ethylene bis(diphenylphosphine)‐incorporated poly(imide) separators for lithium‐ion batteries

AbstractAlthough poly(imide)‐based separators have received great attention as an alternative separator for lithium‐ion batteries, there are serious restrictions because their porous structures enable a great amount of current to leak internally. In this work, we report a one‐step coating process for the structures of poly(imide) (PI)‐based separators that effectively closes their pores. To close the large pores on a PI separator, nanosized aluminum oxide as a coating precursor and the free radical scavenging agent ethylene bis(diphenylphosphine) were co‐incorporated into the PI separator. Screening tests confirmed that ethylene bis(diphenylphosphine) (EPP) can effectively scavenge free radical species via chemical reaction and that incorporating Al2O3–EPP composites closed pores of the PI separators. Regarding electrochemical performance, the cell cycled with a PI separator that incorporated Al2O3–EPP exhibited stable cycling, while the cell cycled with a bare PI separator showed failure. These results indicate that incorporating Al2O3–EPP material effectively increases both safety and electrochemical performance. The Al2O3–EPP composites are incorporated onto the PI separator via dip‐coating process in order to improve electrochemical properties of PI separator. The cell cycled with the Al2O3–EPP incorporated PI separator exhibits stable cycling behavior because Al2O3–EPP composites effectively prevent internal short circuit in the cell.

The NO-dependent caspase signaling pathway is a target of deoxynivalenol in growth inhibition in vitro

DON is commonly found in foods and feeds; it presents health risks, especially an increase of growth inhibition in humans, particularly infants and young children. However, there are relatively few research studies devoted to the mechanism of DON-mediated growth retardation. Interestingly, our results showed that DON does not cause any significant production of ROS but results in a persistent and significant release of NO with iNOS increasing activity, mitochondrial ultrastructural changes and decreasing ΔΨm. Moreover, the significant decreases in GH production and secretion induced by DON were dose-dependent, accompanied by an increase of caspase 3, 8 and 9, IL-11, IL-lβ and GHRH. NO scavenging agent (haemoglobin) and free radical scavenging agent (N-acetylcysteine) partially reversed mitochondrial damage, and Z-VAD-FMK increased the levels of GH and decreased the levels of caspase 3, 8 and 9, while haemoglobin decreased the levels of caspase 3, 8 and 9, indicating that NO is the primary target of DON-mediated inhibition. Present research study firstly demonstrated that NO is a key mediator of DON-induced growth inhibition and plays critical roles in the interference of GH transcription and synthesis. The current research is conducive to future research on the molecular mechanisms of DON-induced growth inhibition in humans, especially children.

Secoiridoid dimers and their biogenetic precursors from the fruits of Cornus officinalis with potential therapeutic effects on type 2 diabetes

Cornusdiridoid A-F (1–6), six unusual cornuside-morroniside secoiridoid dimers, and their possible new biogenetic precursor, 3″,5″-dehydroxycornuside (7), together with four known secoiridoids (8–11), were obtained from the fruits of Cornus officinalis. Their structures were elucidated on the basis of various spectroscopic and chemical methods. A plausible biosynthetic pathway of compounds 1–11 was proposed. The α-glucosidase inhibitory, antioxidant and anti-inflammatory activities of these isolates were evaluated. Some of them emerged out as potent antidiabetic, anti-inflammatory and free radical scavenging agents. Molecular docking was also carried out for antidiabetic target α-glucosidase to investigate the possible binding modes of the most potent α-glucosidase inhibitor, vincosamide (9). These results revealed that the secoiridoids from C. officinalis fruits may be served as new potential antidiabetic agents to prevent and treat type 2 diabetes.

Abstract 928: Glypican-3 targeted thorium-227 alpha therapy reduces tumor burden in an orthotopic xenograft model of hepatocellular carcinoma

Abstract The purpose of this study is to develop a thorium-227 (227Th) antibody radioimmunoconjugate targeting glypican-3 (GPC3) and to test its therapeutic efficacy in a hepatocellular carcinoma (HCC) orthotopic xenograft model. GPC3 targeting antibody (αGPC3) was conjugated to bifunctional chelator p-SCN-Bn-H4octapa (octapa), and αGPC3-octapa binding affinity for GPC3 was evaluated by flow cytometry. 227Th radiolabeling of this conjugate was optimized, and in vitro stability of 227Th-αGPC3-octapa was evaluated in PBS with and without free radical scavenging agent over 14 days. For in vivo evaluation, an orthotopic xenograft model was generated by hepatic subcapsular injection of human HCC HepG2 cells. In vivo biodistribution was assessed in blood, tumor and organs at 1, 7 and 21 days after tail vein injection of 227Th-αGPC3-octapa (500 KBq/kg). To test therapeutic efficacy, tumor-bearing animals were injected with 227Th-αGPC3-octapa (250 kBq/kg or 500 kBq/kg) and compared to an irrelevant control antibody, 227Th-αBHV1-octapa (500 kBq/kg), and to a no-treatment control. Tumor burden was assessed with serial serum alpha-fetoprotein (AFP) measurements, a marker of tumor burden validated in this model. Toxicity to 227Th-αGPC3-octapa was measured by serum comprehensive metabolic panel obtained 21 days after injection. GPC3 binding affinity was highest after conjugation of αGPC3 with 10 equivalents of octapa. The protein recovery from the conjugation process was >85%, and mass spectral analysis indicated an average of 3.3 octapa moieties per molecule of αGPC3-octapa. After two weeks, >98% of αGPC3-octapa and αBHV1-octapa had 227Th bound in the presence of scavenging agent. αGPC3-octapa maintained high affinity for GPC3 as measured by flow cytometry, indicating the octapa conjugation reaction did not alter immunoreactivity of αGPC3. In vivo, 227Th-αGPC3-octapa accumulated in the tumor over time and cleared from normal tissues with a %ID/g of <5% by 21 days after injection. Significant antitumor activity was observed after treatment with 227Th-αGPC3-octapa (500 kBq/kg) with mean AFP level of 10,696 ± 19,754ng/mL compared to 308,175 ± 362,372ng/mL and 145,154 ± 166,780ng/mL in the 227Th-αBHV1-octapa and no-treatment control group, respectively. Reductions in serum AFP was observed in all but one tumor-bearing mouse after 500kBq/kg 227Th-αGPC3-octapa therapy. Organ-specific toxicity was not observed after treatment with 227Th-αGPC3-octapa (500 KBq/kg) compared to no-treatment control. In conclusion, we report the development of a GPC3 targeted thorium conjugate and demonstrate its in vivo therapeutic efficacy in a murine orthotopic xenograft model of hepatocellular carcinoma. Citation Format: Kevin P. Labadie, Donald K. Hamlin, Aimee Kenoyer, Sara K. Daniel, Alan F. Utria, Andrew D. Ludwig, Heidi L. Kenerson, Delphine L. Chen, Johnnie Orozco, Raymond S. Yeung, Lily Li, Chris Orvig, Yawen Li, D Scott Wilbur, James O. Park. Glypican-3 targeted thorium-227 alpha therapy reduces tumor burden in an orthotopic xenograft model of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 928.

Determination of New IR and UV/VIS Spectroscopic Parameters of the C84-D2:22 Isomer for Its Quantitative Assessment, Identification and Possible Applications

The stable isomers of the higher fullerenes C76-D2 and C84-D2:22, as well as fullerenes C60 and C70 were isolated from carbon soot by the new and improved extraction and chromatographic methods and processes. Characterizations of the C84-D2:22 isomer in this study were performed by infrared and electronic absorption spectroscopy. All of the experimentally observed IR and UV/VIS bands were in excellent agreement with the semi-empirical, DFT and TB potential theoretical calculations for this molecule. The molar extinction coefficients and the integrated molar extinction coefficients of the observed larger number of completely separated infrared absorption maxima and shoulders of fullerene C84-D2:22, as well as of its main convoluted maxima, in different and new relevant entire integration ranges, including neighboring, and all surrounding absorption shoulders were determined and their relative intensities compared. In addition, the molar absorptivity of the electronic absorption bands of this carbon cluster was found. The new IR and UV/VIS spectroscopic parameters that are significant for the quantitative determination, identification and numerous possible applications of C84-D2:22 are obtained and their changes compared to C76-D2 observed. Isolated and characterized C84-D2:22, as well as other fullerenes from this research can be used in electronic, optical, chemical and biomedical devices, superconductors, semiconductors, batteries, catalysts, polymers, sensors, solar cells, nanophotonic lenses with better optical transmission, refraction and wettability, diagnostic and therapeutic pharmaceutical substances, such as those against diabetes, cancer, neurodegenerative disorders, free radical scavenging, radio nuclear, antibacterial and antiviral agents that can inhibit HIV 1, HSV, COVID-19, influenza, malaria and so forth.

Efficacy of Ashwagandha (withania somnifera [l.] Dunal) in improving cardiorespiratory endurance (VO2 max test) in healthy subjects

In Ayurveda, certain herbal formulas are considered to be Rasayana and they are typically taken over periods of time to regenerate both brain and body tissue. Ashwagandha (Withania Somnifera) is used as an adaptogen, antioxidant, immune modulator, free radical scavenger, anti stress, anti arthritic, antispasmodic, anti inflammatory, nervous tonic, nerve soothing and anticancer agent. Ashwagandha (WS) as a nutritional supplement is yet too established. Maximum oxygen uptake (VO2 max) is a gold standard of cardiopulmonary and muscle cell fitness is considered. The study evaluated the efficacy of Ashwagandha to improve cardiorespiratory endurance (VO2 max) in healthy subjects. They randomized single blind controlled comparative clinical study. 54 health volunteers in each group, study group received Ashwagandha Choorna 12gm with milk (200ml) empty stomach in the morning and the control group only milk (200ml). Maximal capacity of oxygen intake in ml/kg/min (VO2 max) with Rockport fitness walking test of both study and control group were measured before intervention (0th day), after the intervention (60th day) and follow up (90th day). A significant improvement in the VO2 max (F=20.675, P <0.0001) and Hemoglobin (X2=74.150 P <0.0001) in the study group was found. Supplementation of Ashwagandha (Withania Somnifera) with milk improve hemoglobin and VO2 max (maximum aerobic capacity).

<p><strong>Effect of edaravone on lungs and small intestine in rats with induced radiotherapy</strong></p>

Radiotherapy is a frequently used method for treatment of cancer which is regarded as one of the top two diseases causing premature death worldwide. However, radiotherapy is known to have many side effects. In this study, we evaluated biologically and histologically the possible protective effects of edaravone, the free radical scavenger and neuroprotective agent used to treat amyotrophic lateral sclerosis, on lung and small intestine against radiation-induced early side effects of 15 Gy total body irradiation in single fraction. Thirty-two rats were divided randomly into four equal groups. Groups were administered 15 Gy of external ionizing radiation to the whole body after 30 minutes of EDA administration (a dose of 500 and 50 mg/kg). Rats were sacrified at 72 h of the experiment. Tissues were separated to investigate levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPX) and malondialdehyde (MDA); and evealuate histopathological changings. The protective effect of EDA showed statistically significant in MDA, SOD and GSHPX values of lungs except CAT and statistically significant effect was observed in MDA in small intestine. Also, we showed statistically significant values with histopathological changings. Pediatric cancer patients who have a longer life expectancy are as important as their recovery from their normal life. We are expecting that EDA as a modulator of free radical scavenging pathways in many organs can reduce the side effects of radiation damage on lungs and small intestine.

Hydroxy-tyrosol as a Free Radical Scavenging Molecule in Polymeric Hydrogels Subjected to Gamma-Ray Irradiation

Biomedical engineering is employing hydrogels with increasingly exciting possibilities for the treatment and regeneration of pathologically altered, degenerated, or traumatized tissues. Still, the sterilization processes may undesirably change the chemical and physical properties of hydrogels through cross-linking reactions. This work aims to characterize a new method of producing polyethylene oxide (PEO) hydrogels exploiting hydroxy-tyrosol (HT), an anti-oxidant molecule derived from olive leaf and olive oil, as a free radical scavenger to either prevent or limit gamma-ray-induced cross-linking. For this purpose, we produced hydrogels with PEO with two different buffer solutions (phosphate and citrate), varying HT concentration. We analyzed hydrogel preparations before and after gamma-ray irradiation, assessing the viscosity through rheological analysis and the chemical changes through IR analysis. We performed high-performance liquid chromatography (HPLC) analysis to measure residual HT in hydrogels after irradiation. The obtained results show that radiation-induced cross-linking and increase in viscosity of PEO hydrogels can be prevented by tailoring the concentration of HT as a free radical scavenging agent. Irradiation only consumes small amounts of HT; its presence in polymeric hydrogels can significantly impact biomedical applications by its anti-oxidant and anti-microbial activities.

Survival from paraquat induced renal impairment in a 17 years old male

N, N’-dimethyl-4, 4’-bipyridinium dichloride (paraquat) is a herbicide commonly used in India that leads to fatal outcome on ingestion. Paraquat interferes in the intracellular electron transfer systems inhibiting the reduction of NADP to NADPH resulting in accumulation of superoxide radical causing lipid cell membranes destruction leading to various organ damage. Life threatening effects such as acute kidney injury as paraquat elimination is mainly by kidney, acute respiratory distress syndrome and multi-organ failure are the causes of mortality in paraquat poisoning. There is no specific antidotes for paraquat poisoning so prevention and aggressive decontamination remains the mainstay of management in case of exposure or ingestion. Paraquat poisoning presentation may vary in cases depending on the amount of paraquat consumed and thus the outcome. Here we report a case of a 17 years old male who presented with acute kidney injury following ingestion of paraquat in a suicidal attempt. In our case, induced vomiting of the stomach content readily after ingestion of the poison, early haemodialysis, use of immunosuppression such as methylprednisolone, cyclophosphamide and antioxidants such as acetylcysteine, Vitamin C and Vitamin E as free radical scavenging agent , supportive measures such as adequate hydration and antibiotics might have helped in the patient’s survival. The case fatality remains very high in paraquat poisoning till date owing to lack of effective treatment options.

The positive effect of eugenol on acute pancreatic tissue injury: a rat experimental model.

Introductionwe present a rat experimental model used to evaluate the possible reduction in the extent of pancreatic tissue injury in acute pancreatitis cases, after administration of eugenol.Methodsone hundred and twenty Wistar rats were used, which were randomly assigned in 3 groups: sham (n=20), control (n=50) and eugenol (n=50). Acute pancreatitis was induced by biliopancreatic ligation in the control and eugenol groups, but not in the Sham group. In the eugenol group, eugenol was administered per-os. Five histopathological parameters, such as edema, inflammatory infiltration, duct dilatation, hemorrhage and acinar necrosis were evaluated.Resultsat 72 h from acute pancreatitis induction, the total histological score was diminished in the eugenol group (p<0.0005) and duct dilatation and inflammatory infiltration were reduced compared to the control group (p<0.05). In addition, at 72 h, eugenol reduced pancreatic myeloperoxidase activity (p<0.0005).Conclusioneugenol, a highly free radical scavenger agent, may have a preventive role in acute pancreatic injury, as it was evident in our rat experimental model.

The effect of Myrmecodia pendans extract toward gastric histology in white rats treated with toxic dose of gentamicin: a preliminary report

Introduction: Myrmecodia pendans, or traditionally known as ant nest fruit, is one of popular traditional medicines in Indonesia with a wide range of effects such as antidiabetic, anticancer, and free-radical scavenging agents. Despite of the extensive research, reports regarding its toxicity are scarce. Gentamicin is also one of popular and widely used anti-biotic but it is associated with a wide range of toxicity, especially if administered at high dose. Therefore, this study aimed to evaluate the effect of Myrmecodia pendans extract in the mice what received toxic dose of gentamicin.Method: 24 male white rats were used and randomly divided into 4 groups: P0 (negative control), P1 (100 mg/kgBW intraperitoneal gentamicin), P2 (gentamicyn + 250 mg/kgBW myrmercodia extract), P3 (250 mg/kgBW myrmercodia extract which administered for 7 days and followed by gentamicin). The treatment was given for 10 days and all mice were sacrificed at the end of the study. The stomach was taken from each mouse and examined pathologically using Hematoxylin-Eosin (HE) staining.Results: The necrosis was found in all groups that received gentamicin (P1-P3) with P2 had the most severe necrosis. Hemorrhage was only found in group that received Myrmecodia extract (P2 and P3) and, again, P2 had higher score of hemorrhage compared to P3.Conclusion: The administration of Myrmecodia extract at 250 mg/kgBW together with toxic dose of gentamicin exacerbate the gastric tissue damage in Wistar rats.