Betula pendula Leaf Extract Targets the Interplay between Brain Oxidative Stress, Inflammation, and NFkB Pathways in Amyloid Aß1-42-Treated Rats.

Alzheimer's disease (AD) is known as the primary and most common cause of dementia in the middle-aged and elderly population worldwide. Chemical analyses of B. pendula leaf extract (BPE), performed using spectrophotometric and chromatographic methods (LC/MS), revealed high amounts of polyphenol carboxylic acids (gallic, chlorogenic, caffeic, trans-p-coumaric, ferulic, and salicylic acids), as well as flavonoids (apigenin, luteolin, luteolin-7-O-glucoside, naringenin, hyperoside, quercetin, and quercitrin). Four groups of Wistar rats were used in this experiment (n = 7/group): control (untreated), Aß1-42 (2 µg/rat intracerebroventricular (i.c.v.), Aß1-42 + BPE (200 mg/Kg b.w.), and DMSO (10 µL/rat). On the first day, one dose of Aß1-42 was intracerebroventricularly administered to animals in groups 2 and 3. Subsequently, BPE was orally administered for the next 15 days to group 3. On the 16th day, behavioral tests were performed. Biomarkers of brain oxidative stress Malondialdehyde (MDA), (Peroxidase (PRx), Catalase (CAT), and Superoxid dismutase (SOD) and inflammation (cytokines: tumor necrosis factor -α (TNF-α), Interleukin 1ß (IL-1ß), and cyclooxygenase-2 (COX 2)) in plasma and hippocampus homogenates were assessed. Various protein expressions (Phospho-Tau (Ser404) (pTau Ser 404), Phospho-Tau (Ser396) (pTau Ser 396), synaptophysin, and the Nuclear factor kappa B (NFkB) signaling pathway) were analyzed using Western blot and immunohistochemistry in the hippocampus. The results show that BPE diminished lipid peroxidation and neuroinflammation, modulated specific protein expression, enhanced the antioxidant capacity, and improved spontaneous alternation behavior, suggesting that it has beneficial effects in AD.

New Copper Complexes with Antibacterial and Cytotoxic Activity.

The discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu4(L1)4(OH)4(DMF)2(H2O)] (C1) (HL1 = N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-benzenesulfonamide) and [Cu(L2)2(phen)(H2O)] (C2) (HL2 = N-(5-(4-methylphenyl)-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the two complexes, the molecules from the reaction medium (phenantroline, dimethylformamide and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR and UV-Vis spectroscopy. Using the microdilution method, the antibacterial activity of the complexes was determined against four Gram-positive and two Gram-negative bacteria, with Gentamicin as the positive control. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, DLD-1) and on a normal cell line (HFL1) using the MTT method and Cisplatin as a positive control. Flow cytometric assessment of apoptosis induced by the complexes on the three cell lines was also performed. Both complexes present in vitro biological activities but complex C2 is more active.

The evaluation of the osteopromoting capabilities of composites based on biopolymers and gold/silver nanoparticles doped bioactive glasses on an experimental rat bone defect.

The most important concept behind using bone scaffolds is the biocompatibility of the material to avoid a local inflammatory response and must have the following properties: osteoinduction, osteoconductivity, angiogenesis, and mechanical support for cell growth. Gold nanoparticles/gold and silver nanoparticles -containing bioactive glasses in biopolymer composites have been used to enhance bone regeneration. These composites were testedin vitroon fibroblast and osteoblast cell lines using MTT tests, immunofluorescence, scanning electron microscopy analysis, andin vivoin an experimental bone defect in Sprague-Dawley rats. Both composites promoted adequate biological effects on human fibroblastic BJ (CRL 2522TM) cell lines and human osteoblastic cells isolated from the human patella in terms of cell proliferation, morphology, migration, and attachment. Most importantly, they did not cause cellular apoptosis and necrosis. According to the histological and immunohistochemical results, both composites were osteoinductive and promoted new bone formation at 60 d. Evidence from this study suggests that the small amount of silver content does not influence negatively thein vitroorin vivoresults. In addition, we obtained accurate results proving that the existence of apatite layer and proteins on the surface of the recovered composite, supports the validity ofin vitrobioactivity research.

Metallo-Drugs in Cancer Therapy: Past, Present and Future.

Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities include inherent resistance, systemic toxicity and severe side effects. Out of 50% patients administrated to chemotherapy, only 5% survive. For these reasons, the identification of new drug designs and therapeutic strategies that could target cancer cells while leaving normal cells unaffected still continues to be a challenge. Despite advances that have led to the development of new therapies, treatment options are still limited for many types of cancers. This review provides an overview of platinum, copper and ruthenium metal based anticancer drugs in clinical trials and in vitro/in vivo studies. Presumably, copper and ruthenium complexes have greater potential than Pt(II) complexes, showing reduced toxicity, a new mechanism of action, a different spectrum of activity and the possibility of non-cross-resistance. We focus the discussion towards past, present and future aspects.

New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents.

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu(L1)2(H2O)3] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide) and [Cu(L2)2(py)2(H2O)] (C2) (HL2= N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes' capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

Experimental model for controlled endoscopic subepithelial vocal fold injury in rats.

PURPOSE: To present a detailed, reproducible, cost-efficient surgical model for controlled subepithelial endoscopic vocal fold injury in the rat model. METHODS: Six male Sprague Dawley rats were enrolled in the experiment. The left vocal folds were used to carry out the injury model, and the right vocal fold served as control. After deep sedation, the rats were placed on a custom operating platform. The vocal fold injury by subepithelial stripping was carried out using custom-made microsurgical instruments under endoscopic guidance. Data were analyzed for procedural time and post-procedural pain. Microcomputed tomography (micro-CT) scan and histologic images were obtained to assess the length, area, and depth of injury to the vocal fold. RESULTS: The mean procedural time was 112 s. The mean control vocal fold length was 0.96 ± 0.04 mm. The mean vocal fold injury length was 0.53 ± 0.04 mm. The mean vocal fold surface was 0.18 ± 0.01 mm2 with a mean lesion area of 0.05 ± 0.00 mm2. Mean vocal fold injury depth was 375.4 ± 42.8 µm. The lesion length to vocal fold length ratio was 0.55 ± 0.03, as well as lesion area to vocal fold surface area was 0.29 ± 0.02. CONCLUSIONS: Our described experimental vocal fold injury model in rats is found to be fast, safe, cost-efficient, and reproducible with a rapid learning curve.

Glutaraldehyde-Polymerized Hemerythrin: Evaluation of Performance as an Oxygen Carrier in Hemorrhage Models.

Hemoglobin-based oxygen carriers (HBOCs) have been proposed and tested for several decades for the treatment of hemorrhage. We have previously proposed replacing hemoglobin (Hb) in HBOC with the oxygen-carrying protein hemerythrin (Hr), from marine worms, showing that Hr-based derivatives can perform at least as well or even better than Hb-based HBOC in a range of in vitro assays involving oxidative and nitrosative stress as well as in top-up animal models, where small amounts of Hr- or Hb-HBOC were injected into rats. Here, these experiments are extended to a hemorrhage experiment, in which Hr polymerized with glutaraldehyde, alone or conjugated with human serum albumin, is administered after a loss of 20-30% blood volume. The performance of these preparations is compared with that of Hb-based HBOC measured under the same conditions. Polymerized Hr is found to decrease the survival rate and can hence cannot be used as an oxygen carrier in transfusions. On the other hand, an Hr-albumin copolymer restores survival rates to 100% and generally yields biochemical and histological parameters similar to those of glutaraldehyde-polymerized bovine hemoglobin, with the exception of an acid-base imbalance. The latter may be solved by employing an allogeneic albumin as opposed to the human albumin employed in the present study.

Experimental model for controlled endoscopic subepithelial vocal fold injury in rats

Purpose: To present a detailed, reproducible, cost-efficient surgical model for controlled subepithelial endoscopic vocal fold injury in the rat model. Methods: Six male Sprague Dawley rats were enrolled in the experiment. The left vocal folds were used to carry out the injury model, and the right vocal fold served as control. After deep sedation, the rats were placed on a custom operating platform. The vocal fold injury by subepithelial stripping was carried out using custom-made microsurgical instruments under endoscopic guidance. Data were analyzed for procedural time and post-procedural pain. Microcomputed tomography (micro-CT) scan and histologic images were obtained to assess the length, area, and depth of injury to the vocal fold. Results: The mean procedural time was 112 s. The mean control vocal fold length was 0.96 ± 0.04 mm. The mean vocal fold injury length was 0.53 ± 0.04 mm. The mean vocal fold surface was 0.18 ± 0.01 mm2 with a mean lesion area of 0.05 ± 0.00 mm2. Mean vocal fold injury depth was 375.4 ± 42.8 µm. The lesion length to vocal fold length ratio was 0.55 ± 0.03, as well as lesion area to vocal fold surface area was 0.29 ± 0.02. Conclusions: Our described experimental vocal fold injury model in rats is found to be fast, safe, cost-efficient, and reproducible with a rapid learning curve.

Evaluation of Hepatoprotective Activity and Oxidative Stress Reduction of Rosmarinus officinalis L. Shoots Tincture in Rats with Experimentally Induced Hepatotoxicity.

Rosmarinus officinalis L. is a widely known species for its medicinal uses, that is also used as raw material for the food and cosmetic industry. The aim of the present study was to offer a novel perspective on the medicinal product originating from this species and to test its hepatoprotective activity. The tested sample consisted in a tincture obtained from the fresh young shoots. Compounds that are evaluated for this activity are polyphenols and terpenoids, that are identified and quantified by HPLC-UV-MS and GC-MS. Antioxidant activity was assessed in vitro, using the DPPH, FRAP and SO assays. Hepatoprotective activity was tested in rats with experimentally-induced hepatotoxicity. In the chemical composition of the tincture, phenolic diterpenes (carnosic acid, carnosol, rosmanol, rosmadial) and rosmarinic acid were found to be the majority compounds, alongside with 1,8-cineole, camphene, linalool, borneol and terpineol among monoterpenes. In vitro, the tested tincture proved significant antioxidant capacity. Results of the in vivo experiment showed that hepatoprotective activity is based on an antioxidant mechanism. In this way, the present study offers a novel perspective on the medicinal uses of the species, proving significant amounts of polyphenols and terpenes in the composition of the fresh young shoots tincture, that has proved hepatoprotective activity through an antioxidant mechanism.

Bioactive glass-biopolymers­gold nanoparticle based composites for tissue engineering applications.

Biomaterials based on bioactive glass with gold nanoparticle composites have many applications in tissue engineering due to their tissue regeneration and angiogenesis capacities. The objectives of the study were to develop new composites using bioactive glass with gold nanospheres (BGAuSP) and gold nanocages (BGAuIND), individually introduced in alginate-pullulan (Alg-Pll) polymer, to evaluate their biocompatibility potential, and to compare the obtained results with those achieved when ß-tricalcium phosphate-hydroxyapatite (ßTCP/HA) replaced the BG. The novel composites underwent structural and morphological characterization followed by in vitro viability testing on fibroblast and osteoblast cell lines. Additionally, the biomaterials were subcutaneously implanted in Sprague Dawley rats, for in vivo biocompatibility assessment during 3 separate time frames (14, 30 and 60 days). The biological effects were evaluated by histopathology and immunohistochemistry. The physical characterization revealed the cross-linking between polymers and glasses/ceramics and demonstrated a suitable thermal stability for sterilization processes. The in vitro assays demonstrated adequate form, pore size of composites ranging from few micrometers up to 100 µm, while the self-assembled apatite layer formed after simulated body fluid immersion confirmed the composites' bioactivity. Viability assays have highlighted optimal cellular proliferation and in vitro biocompatibility for all tested composites. Furthermore, based on the in vivo subcutaneous analyses the polymer composites with BGAuNP have shown excellent biocompatibility at 14, 30 and 60 days, exhibiting marked angiogenesis while, tissue proliferation was confirmed by high number of Vimentin positive cells, in comparison with the polymer composite that contains ßTCP/HA, which induced an inflammatory response represented by a foreign body reaction. The obtained results suggest promising, innovative, and biocompatible composites with bioactive properties for future soft tissue and bone engineering endeavours.

Glutaraldehyde-Polymerized Hemoglobin: In Search of Improved Performance as Oxygen Carrier in Hemorrhage Models.

Hemoglobin- (Hb-) based oxygen carriers (HBOC) have for several decades been explored for treatment of hemorrhage. In our previous top-up tests, HBOC with lower in vitro prooxidant reactivity (incorporating a peroxidase or serum albumin to this end) showed a measurable but small improvement of oxidative stress-related parameters. Here, such HBOCs are tested in a hemorrhage set-up; ovine hemoglobin is also tested for the first time in such a setting, based on in vitro data showing its improved performance versus bovine Hb against oxidative and nitrosative stress agents. Indeed, ovine Hb performs better than bovine Hb in terms of survival rates, arterial tension, immunology, and histology. On the other hand, unlike in the top-up models, where the nonheme peroxidase rubrerythrin as well as bovine serum albumin copolymerized with Hb were shown to improve the performance of HBOC, in the present hemorrhage models rubrerythrin fails dramatically as HBOC ingredient (with a distinct immunological reaction), whereas serum albumin appears not feasible if its source is a different species (i.e., bovine serum albumin fares distinctly worse than rat serum albumin, in HBOC transfusions in rats). An effect of the matrix in which the HBOCs are dissolved (PBS versus gelofusine versus plasma) is noted.

Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders. AIM OF THE STUDY: To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ. MATERIAL AND METHODS: Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-ß-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg2+), calcium (Ca2+), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1C) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed. RESULTS: At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 µg/mg of extract) and quercitrin (19.07 µg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein. CONCLUSIONS: Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum.

Systemic and Local Biocompatibility Assessment of Graphene Composite Dental Materials in Experimental Mandibular Bone Defect.

The main objective of this research is to demonstrate the biocompatibility of two experimental graphene dental materials by in vitro and in vivo tests for applications in dentistry. The novel graphene dental materials, including one restorative composite and one dental cement, were subjected to cytotoxicity and implantation tests by using a rat model of a non-critical mandibular defect. In vitro cytotoxicity induced by materials on human dental follicle stem cells (restorative composite) and dysplastic oral keratinocytes (dental cement) was investigated at 37 °C for 24 h. After in vivo implantation, at 7 weeks, bone samples were harvested and subjected to histological investigations. The plasma biochemistry, oxidative stress, and sub-chronic organ toxicity analysis were also performed. The resulting cytotoxicity tests confirm that the materials had no toxic effects against dental cells after 24 h. Following graphene dental materials implantation, the animals did not present any symptoms of acute toxicity or local inflammation. No alterations were detected in relative organ weights and in correlation with hepatic and renal histological findings. The materials' lack of systemic organ toxicity was confirmed. The outcomes of our study provided further evidence on the graphene dental materials' ability for bone regeneration and biocompatibility.

Detection of DNA of Babesia canis in tissues of laboratory rodents following oral inoculation with infected ticks.

BACKGROUND: Babesia spp. are apicomplexan parasites which infect a wide range of mammalian hosts. Historically, most Babesia species were described based on the assumed host specificity and morphological features of the intraerythrocytic stages. New DNA-based approaches challenge the traditional species concept and host specificity in Babesia. Using such tools, the presence of Babesia DNA was reported in non-specific mammalian hosts, including B. canis in feces and tissues of insectivorous bats, opening questions on alternative transmission routes. The aim of the present study was to evaluate if B. canis DNA can be detected in tissues of laboratory rodents following oral inoculation with infected ticks. METHODS: Seventy-five questing adult Dermacentor reticulatus ticks were longitudinally cut in two halves and pooled. Each pool consisted of halves of 5 ticks, resulting in two analogous sets. One pool set (n = 15) served for DNA extraction, while the other set (n = 15) was used for oral inoculation of experimental animals (Mus musculus, line CD-1 and Meriones unguiculatus). Blood was collected three times during the experiment (before the inoculation, at 14 days post-inoculation and at 30 days post-inoculation). All animals were euthanized 30 days post-inoculation. At necropsy, half of the heart, lung, liver, spleen and kidneys were collected from each animal. The presence of Babesia DNA targeting the 18S rRNA gene was evaluated from blood and tissues samples. For histopathology, the other halves of the tissues were used. Stained blood smears were used for the light microscopy detection of Babesia. RESULTS: From the 15 pools of D. reticulatus used for the oral inoculation, six were PCR-positive for B. canis. DNA of B. canis was detected in blood and tissues of 33.3% of the animals (4 out of 12) inoculated with a B. canis-positive pool. No Babesia DNA was detected in the other 18 animals which received B. canis-negative tick pools. No Babesia was detected during the histological examination and all blood smears were microscopically negative. CONCLUSIONS: Our findings demonstrate that B. canis DNA can be detected in tissues of mammalian hosts following ingestion of infected ticks and opens the question of alternative transmission routes for piroplasms.

Bone regeneration response in an experimental long bone defect orthotopically implanted with alginate-pullulan-glass-ceramic composite scaffolds.

In the present study, scaffolds based on alginate-pullulan-bioactive glass-ceramic with 0.5 and 1.5 mol % copper oxide were orthotopically implanted in experimental rat models to assess their ability to heal an induced bone defect. By implying magnetic resonance and imaging scans together with histological evaluation of the processed samples, a progressive healing of bone was observed within 5 weeks. Furthermore, as the regenerative process continued, new bone tissue was formed, enhancing the growth of irregular bone spicules around the scaffolds. A significantly higher amount of new bone was formed (37%) in the defect that received the composite with 1.5 mol % CuO (in glass-ceramic matrix) content implant. Nevertheless, the bone regeneration obtained by scaffold with 0.5 mol % CuO implanted is comparable with the alginate-pullulan-ß-tricalcium phosphate/hydroxiapatite composite implant. The assessed amount of new bone formed was found to be between 29.75 and 37.15% for all the composition involved in the present study. During this process a regeneration process was shown when the alginate-pullulan composite materials were involved, fact that indicate the great potential of these materials to be used in tissue engineering.

Remarkable rutin-rich Hypericum capitatum extract exhibits anti-inflammatory effects on turpentine oil-induced inflammation in rats.

BACKGROUND: Natural extracts with beneficial biological activities are nowadays of high interest, in various treatment or prophylaxis. Hypericum capitatum has been known for its curative effects for centuries and its extracts have become of interest due to their distinct activity among other Hypericaceae members. In this study, further light is aimed to be shed on the secondary-metabolites composition of H. capitatum extracts, using chromatographic techniques and Electron paramagnetic resonance profiles in alkaline medium. Considering that no previous works explored the anti-inflammatory activity of H. capitatum, here, an in vivo study is also designed in order to evaluate this property by assessing the impact of one of H. capitatum extracts in ameliorating turpentine oil-induced inflammation on rats and to quantify their blood antioxidants level. METHODS: Chromatographic techniques and Electron paramagnetic resonance spectroscopy were used in order to describe the chemical profile in different parts of the plant. The in vivo study on turpentine-oil induced inflammation in rats included three doses of H. capitatum extract expressed in rutin concentration. Oxidative stress was measured using total oxidative status, total antioxidant capacity, oxidative stress index, 3-nitrotyrosine, nitric oxide, malondialdehyde, superoxide dismutase, catalase and the inflammatory response was evaluated by performing a complete blood cells count and C reactive protein. RESULTS: The extract was remarkably rich in rutin; however, other polyphenolic-like minor components appeared important in explaining the observed biological properties. The tested extract prevents the increase of inflammation-induced white blood cell count, number of neutrophils, and serum nitric oxide, and did so in a dose-dependent manner, similarly to the positive control-diclofenac. In addition, the same extract appeared to be a good alternative to diclofenac to restore total oxidative status, thiobarbituric active reactive species, total proteins and C reactive proteins. Moreover, antioxidant enzymes such as catalase, superoxide dismutase and total serum thiol concentration were significantly increased by the tested extract. CONCLUSIONS: Due to its powerful reservoir rich in rutin, H. capitatum extract depicted its in vivo antioxidant and anti-inflammatory effects indicating it to be a good alternative to conventional drugs for oxidative stress protection.

Protective effect of blackthorn fruits (Prunus spinosa) against tartrazine toxicity development in albino Wistar rats.

BACKGROUND: Tartrazine (Yellow 5 or E102) is a synthetic food dye able to modify perception and behavior, causing agitation, confusion, rhinitis and can produce hyperactivity syndrome in children when is combined with benzoates. Additionally, it can trigger oxidative stress which consequently generates metabolic disorders. Therefore, the study was designed to evaluate the harmful effects of the food additive tartrazine and to observe beneficial properties of blackthorn fruits (Prunus spinosa) on the blood and organs of albino Wistar rats. MATERIALS AND METHODS: This study was carried out on 20 mature Wistar rats, randomly divided into four groups of five animals. Over the course of the experiment, the control group received only food and drinking water, group I received 75 mg of tartrazine dissolved in (250 ml) water group II was given 75 mg of tartrazine and 200 mg of dried blackthorn fruit powder 200 mg dissolved simultaneously in (250 ml) of tartrazine-water mixture (aiming to reduce the tartrazine toxicity) and group III received a higher dose of tartrazine (100 mg) in (250 ml) of water. RESULTS: At the end of the experiment, values regarding kidney and liver weight were significantly increased, while the weight of the spleen was slightly decreased compared with the weight of the control group. Biochemical and hematological assays, of the blood samples show that the addition of tartrazine in the diet of rats caused significant changes in all biochemical and hematological parameters of the blood. In the group II, which received (P. spinosa) powder combined with tartrazine, the biochemical and hematological parameters had average values similar to the control group. CONCLUSIONS: Histopathological assay showed that the application of tartrazine in the group I, II and III produced lesions of the kidneys, spleen and the liver for all rodents. Tartrazine was able to generate histopathological changes, which caused significantly tissue lesions of the liver and significant changes in blood parameters. Blackthorn powder showed a promising protective role for the blood parameters but demonstrated no significant benefits for the organs.

In Vivo Pharmacological and Anti-inflammatory Evaluation of Xerophyte Plantago sempervirens Crantz.

Known for centuries throughout the world, Plantago species have long been used as traditional herbal remedies for many diseases related to inflammatory conditions of the skin, respiratory and digestive tract, or even malignancy. This study is aimed first at investigating the in vitro antioxidant and regenerative effects of Plantago sempervirens Crantz hydroalcoholic extract followed by an in vivo experiment using a turpentine oil-induced inflammation model. The in vitro evaluation for antioxidant activity was performed using classical assays such as DPPH and TEAC scavenging assays but also EPR, and the total phenolic content was determined using the Folin-Ciocalteu reagent. The wound healing assay was performed on human cells (Human EA.hy926). Besides, the prooxidant activity was determined using a method which involves in situ free radical generation by laccase and the oxidation of haemoglobin. On turpentine oil-induced inflammation in rats, the in vivo effects of three doses of P. sempervirens extracts (100%, 50%, and 25%) were assessed by measuring oxidative stress (MDA, TOS, OSI, NO, CAT, and SOD) and inflammatory (CRP, WBC, and NEU) parameters. Having a rich polyphenolic content, the xerophyte P. sempervirens exhibited a strong in vitro antioxidant activity by scavenging radicals, enhancing cell regeneration, and reducing oxidative stress markers. Diluted P. sempervirens extract (25%) exhibited the best antioxidant, wound healing, and anti-inflammatory activity.

New Aspects Towards a Molecular Understanding of the Allicin Immunostimulatory Mechanism via Colec12, MARCO, and SCARB1 Receptors.

The allicin pleiotropic effects, which include anti-inflammatory, anti-oxidant, anti-tumoral, and antibacterial actions, were well demonstrated and correlated with various molecular pathways. The immunostimulatory mechanism of allicin has not been elucidated; however, there is a possible cytokine stimulation from immunoglobulin release caused by allicin. In this study, when Wistar female rats and CD19+ lymphocytes were treated with three different doses of allicin, immunoglobulins, glutathione, and oxidative stress markers were assayed. Molecular docking was performed between S-allylmercaptoglutathione (GSSA)-a circulating form of allicin in in vivo systems formed by the allicin interaction with glutathione (GSH)-and scavenger receptors class A and B from macrophages, as well as CD19+ B lymphocytes. Our data demonstrated a humoral immunostimulatory effect of allicin in rats and direct stimulation of B lymphocytes by S-allyl-mercapto-glutathione, both correlated with decreased catalase (CAT) activity. The molecular docking revealed that S-allyl-mercapto-glutathione interacting with Colec12, MARCO (class A), and SCARB1 (class B) scavenger receptors in in vitro tests demonstrates a direct stimulation of immunoglobulin secretion by GSSA in CD19+ B lymphocytes. These data collectively indicate that GSSA stimulates immunoglobulin secretion by binding on scavenger receptors class B type 1 (SCARB1) from CD19+ B lymphocytes.

Complications of cataract surgery in Wistar rats undergoing treatment with tamsulosin.

The aim of the study was to identify if there is a connection between the time of administration of alpha-blocker medication and cataract surgery complications. Furthermore, it was explored whether discontinuation of tamsulosin before cataract surgery influences the manifestations of intraoperative floppy iris syndrome in rats. An experimental study was conducted on 20 male Wistar rats aged 1.5-2 years (body mean weight 357 g), which were divided into four equal groups: Group 1, under tamsulosin hydrochloride 0.4 mg/day for 2 months; group 2, without any treatment in the first month, followed by tamsulosin; group 3, under tamsulosin for 1 month, followed by 1 month without any treatment; and group 4, control. The pupillary diameter was assessed before instillation of 0.5% tropicamide (mydriatic and cycloplegic agent), after 1 or 2 h from instillation and postoperatively. Furthermore, pupil constriction during surgery, the presence of floppy iris and prolapse of the iris following the main incision and during serum injection were also assessed. Other analyzed features included iris rupture, posterior capsule tear, vitreous loss, lens fragments in the vitreous, suprachoroidal bleeding and corneal haze. The iris dilator muscle thickness and the posterior epithelium was measured using light microscopy. In the control group, the largest pupillary diameters were indicated and in group 1, the smallest pupillary diameters were revealed. Statistically significant differences were indicated between group 1 and 2 and group 3 and 4. Floppy iris, iris prolapse in the main incision and during serum injection appeared at maximum frequency for group 1 with continuous treatment and low frequency for the control group. Lens fragments in the vitreous were present in the groups 1-3. Notably, intraoperative miosis had statistical relevance in group 1 and group 2. To conclude, the present findings suggested there is a clear connection between the time of administration of the alpha-blocker medication and most cataract complications. The results indicated that discontinuation of tamsulosin for one month largely reduces the manifestations of intraoperative floppy iris syndrome in rats, which may suggest to change preoperative treatment for benign prostatic hypertrophy with another class of drugs that do not interact with the iris receptors.