A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs

The extent of susceptibility towards miltefosine (Mil), amphotericin B (AmpB), and paromomycin (Paro) was measured among 19 clinical isolates of Leishmania donovani (LD). Thirteen of these clinical isolates were reported to exhibit low susceptibility towards sodium stibogluconate (SSG-R), while six of them were highly susceptible (SSG-S). The degree of clearance of amastigotes (EC50) for these predefined SSG-R- and SSG-S-infected macrophages was determined against Mil, AmpB, and Paro. Two out of the 13 SSG-R isolates (BHU575 and BHU814) showed low susceptibility towards all three drugs studied, while the rest of the 11 SSG-R isolates showed varying degrees of susceptibility either towards none or only towards individual drugs. Interestingly, all the SSG-S isolates showed high susceptibility towards Mil/AmpB/Paro. The total intracellular non-protein thiol content of the LD promastigotes, which have been previously reported to be positively co-related with EC50 towards SSG, was found to be independent from the degree of susceptibility towards Mil/AmpB/Paro. Impedance spectra analysis, which quantifies membrane resistance, revealed lower impedimetric values for all those isolates exhibiting low efficacy to Mil (Mil-R). Our analysis points out that while non-protein thiol content can be an attribute of SSG-R, lower impedimetric values can be linked with lower Mil susceptibility, although neither of these parameters seems to get influenced by the degree of susceptibility towards AmpB/Paro. Finally, a correlation analysis with established biological methods suggests that impedance spectral analysis can be used for the accurate determination of lower Mil susceptibility among LD isolates, which is further validated in the LD-infected in vivo hamster model.

Antibacterial and antioxidant activities of endophytic fungi and nettle (Urtica dioica L.) leaves as their host

Nettle (Urtica dioica L), as a plant rich in biologically active compounds, is one of the most important plants used in herbal medicine. Studies have shown that this plant has antioxidant, antiplatelet, hypoglycemic and hypocholesterolemia effects. In this study, we characterized three Alternaria endophytic fungi isolated from their host U. dioica. We hypothesized that these endophytic fungi can produce new bioactive metabolites, which may possess the bioactive property with potential application in the medical and pharmaceutical industries. The antibacterial activity was evaluated against reference and isolated strains, including Methicillin-Resistant Staphylococcus aureus. A wide range of antimicrobial activities similar to those measured in nettle leaves was detected especially for Alternaria sorghi. Furthermore, the highest antioxidant activity detected with DPPH free radical scavenging was measured for A. sorghi and nettle leaves ethyl acetate extracts. In addition, whereas catalase activity was similar in the three isolated fungi and nettle leaves, total thiol content and superoxide dismutase activity were significantly higher in leaves. A. sorghi showed the best activities compared to other isolated fungi. The characterization and further production of bioactive compounds produced by this endophyte should be investigated to fight bacteria and especially those that develop drug multi-resistance.

Inhibition of Protein and Lipid Oxidation of Beef Patties by Using Sumac Fruit Extract During Freeze Storage

The fruits of sumac Rhus coriaria L. are widely used in traditional folk medicine as spices and flavors, especially in meats, because they are a rich source of natural antioxidants and also their tremendous potential in improving the quality of meat. The study aimed to use different concentrations of sumac fruits extract ( SFE) prepared with a concentration of control T 0, T1: 0.05% and T2: 0.1% and studying their effect on inhibiting protein and lipid oxidation of beef patties stored in Freeze - 18±1 °C for 90 days. The T2 could significantly inhibit an increased carbonyl content, PV and TBA value (P<0.01) and inhibition of pH value at (P<0.01) while the thiol content and water content significantly (P<0.01) decreased finding. The SFE may be used as natural antioxidant compound in helping to extend the period of meat products.

Fucoid Macroalgae Have Distinct Physiological Mechanisms to Face Emersion and Submersion Periods in Their Southern Limit of Distribution

During high tide, macroalgae are submersed, facing adequate environmental conditions, however, at low tide, these species can be exposed to high UV radiation and desiccation, leading to an overproduction of reactive oxygen species, causing oxidative stress. Since intertidal organisms present differential sensitivity to abiotic fluctuations, this study aimed to evaluate the physiological responses [photosynthetic pigments, hydrogen peroxide (H2O2), lipid peroxidation (LP), and thiols and proline] of three macroalgae, from different intertidal levels, towards tidal regimes. Samples of Pelvetia canaliculata, Ascophyllum nodosum, and Fucus serratus were collected from beaches located on the southern limit of distribution in periods of potential stress (Summer and Spring), under low and high tide. The photosynthetic pigments of P. canaliculata and F. serratus were generally higher during low tide, and the oxidative damage evidenced by H2O2 and LP increased in the Summer, while A. nodosum showed greater oxidative damage in the Spring. While thiol content did not change, proline levels were species- and tidal-specific among sampling dates. P. canaliculata presented higher resilience to unfavorable conditions, while F. serratus was the most sensitive species. The physiological responses analyzed were species-specific, pointing to the high susceptibility of low intertidal organisms to expected extreme climatic events.

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats

Objectives Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. Methods The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. Results The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). Conclusions Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.

Quercetin ameliorates acetamiprid-inducedhepatotoxicity and oxidative stress

Introduction: Neonicotinoids are a new type of insecticides that have been introduced to the poison market during the last three decades. Acetamiprid (ACT) is a neonicotinoid and widely used for controlling pests. It targets the liver as a toxic agent and damages hepatic tissues through oxidative stress mechanisms. Quercetin is a flavonoid with potent antioxidant and hepatoprotective activity and protects tissues from oxidative damages. Thus, this study is aimed to assess the protective effect of quercetin on acetamiprid-induced hepatotoxicity. Methods: Thirty-six Wistar rats were classified into six groups including control, DMSO, ACT 20, ACT 40, quercetin, and ACT40+quercetin. All treatments were administered orally with gavage for 28 days. Alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) enzyme activity was measured in serum as biomarkers of hepatotoxicity. Lipid peroxidation, superoxide dismutase (SOD) enzyme activity and total thiol content were measured in hepatic tissues. Also, hepatic tissue sections were prepared and stained with hematoxylin and eosin and evaluated under optic microscope for any tissue injuries. Results: Findings showed that ACT, especially in high dose (40mg/kg), induced hepatic tissue destruction associated with increased hepatic enzyme activity, except ALP activity, in the serum. Besides, ACT increased the lipid peroxidation and decreased total thiol content and SOD activity, which indicates ACT-induced oxidative stress in hepatic tissues. Also, hepatic tissue injuries were observed in ACT-treated group. All these changes in liver were prevented by quercetin. Conclusion: Because of strong antioxidant properties, quercetin can cope effectively with ACT-induced hepatotoxicity.

Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione

Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups.

The Phytochemical Constituents, Hypoglycemic, and Antioxidant Activities of Senna occidentalis (L.) Ethanolic Leaf Extract in High Sucrose Diet Fed Drosophila melanogaster

Aim: This study was aimed at evaluating the phytochemical constituents,hypoglycemic, and antioxidant activities of Senna occidentalis ethanolic leaf extract in diabetic Drosophila melanogaster with emphasis on survival, phytochemical, biochemical and fecundity assays as well as locomotor activities. Methodology:S. occidentalisleaves was collected and prepared for extraction using 70% ethanol as solvent. The extract was subjected to phytochemical screening and the lethal dose(LD50) was carried out on D. melanogasterfor 7 days. Survival study was conducted by treating fruit flies with different concentration of the extracts for 28 days. Hyperglycemia was induced by feeding the flies with food containing 30% of sucrose for 10 days, and thereafter treated with different concentration of the extract and metformin (positive control) for 7 days.Diabetic flies were used for the negative geotaxis and fecundity assays. The homogenates of flies from the different groups of the treatment and control were prepared and used to quantify the glucose content and the antioxidant activities which included the thiol content, glutathione-s-transferase and catalase activities. Results: The phytochemical screening revealed the presence 8 different phytochemicals. The LD50 was determined to be 277.8 mg/10 g fly food of S. occidentalis. Supplementation with S. occidentalis ethanolic extracts showed a non-significant increase (P> 0.05) in the survival of D melanogaster when compared to the baseline group.Diabetic flies treated withthe extract showed a dose-dependent decrease in serum glucose which was significant (P< 0.05) at 100 mg when compared to the negative control group(untreated). Negative geotaxis, fecundity and catalase activitiesof treated fliesshowed no significant difference (P> 0.05) when compared toflies in the negative control group. S. occidentalis ethanolic leaf extract significantly elevated (P< 0.05) the total thiol content and glutathione-s-transferase activities at certain concentration in a non-linear manner. Conclusion: From the findings, S. occidentalis ethanolic leaf extract contained several phytochemicals and it is relatively safe; possessing hypoglycemic and antioxidant properties when administered to diabeticD. melanogaster.

Folic Acid Attenuated Learning and Memory Impairment via Inhibition of Oxidative Damage and Acetylcholinesterase Activity in Hypothyroid Rats

Hypothyroidism has been associated with cognitive decline. Considering the role that has been suggested for folic acid (FA) in cognitive performance, the present study was designed to investigate the effects of FA against hypothyroidism-induced cognitive impairment, oxidative damage and acetylcholinesterase (AChE) activity alterations in propylthiouracil (PTU)-induced hypothyroid rats. In this study, PTU (0.05% in drinking water) and FA (5, 10, and 15 mg/kg, oral gavage) were administered to the rats for a period of 7 weeks. Then, behavioral performance was tested using Morris water maze (MWM) and passive avoidance (PA) tasks. Finally, oxidative stress indicators and AChE activity were assayed in the brain tissues. The impairing effect of hypothyroidism on cognitive performance was markedly alleviated by FA especially at the higher doses. In the MWM test, FA reduced escape latency and travelled distance, compared to the non-treated hypothyroid group. In the PA test, the latency to enter the dark chamber was significantly enhanced by FA as compared to the non-treated hypothyroid group (p < 0.05-p < 0.001). Besides, FA attenuated AChE activity and malondialdehyde level but increased superoxidase dismutase enzyme activity and total thiol content (p < 0.05-p < 0.001). In conclusion, FA could improve learning and memory ability in hypothyroid rats. The observed protective effects may be mediated through regulation of oxidative stress and AChE activity.