Zootoxins and Domestic Animals: A European View.

Zootoxins are produced by venomous and poisonous species and are an important cause of poisoning in companion animals and livestock in Europe. Little information about the incidence of zootoxin poisoning is available in Europe, with only a few case reports and review papers being published. This review presents the most important zootoxins produced by European venomous and poisonous animal species responsible for poisoning episodes in companion animals and livestock. The main zootoxin-producing animal species, components of the toxins/venoms and their clinical effects are presented. The most common zootoxicoses involve terrestrial zootoxins excreted by the common toad, the fire salamander, the pine processionary caterpillar, and vipers. The lack of a centralized reporting/poison control system in Europe makes the evaluation of the epidemiology of zootoxin-induced poisonings extremely difficult. Even if there are many anecdotal reports in the veterinary community about the exposure of domestic animals to terrestrial and marine zootoxins, the number of published papers regarding these toxicoses is low. Climate change and its consequences regarding species distribution and human-mediated transportation are responsible for the emerging nature of some intoxications in which zootoxins are involved. Although new venomous or poisonous animal species have emerged in regions where they were previously unreported, zootoxins produced by native species remain the main concern in Europe. The diversity of poisonous and venomous animal species and the emerging nature of certain poisonings warrant the continuous update to such knowledge by veterinary professionals and animal owners. This review offers an overview about zootoxin-related poisonings in domestic animals in Europe and also provides important information from a health perspective.

The Nephroprotective Effect of Cornelian Cherry (Cornus mas L.) and Rowanberry (Sorbus aucuparia L.) in Gentamicin-Induced Nephrotoxicity on Wistar Rats with Emphasis on the Evaluation of Novel Renal Biomarkers and the Antioxidant Capacity in Correlation with Nitro-Oxidative Stress.

In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries.

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.

Emerging Plant Intoxications in Domestic Animals: A European Perspective.

Exposure to phytotoxins that are present in imported ornamental or native plants is an important cause of animal disease. Factors such as animal behaviors (especially indoor pets), climate change, and an increase in the global market for household and ornamental plants led to the appearance of new, previously unreported plant poisonings in Europe. This has resulted in an increase in the incidence of rarely reported intoxications. This review presents some of the emerging and well-established plant species that are responsible for poisoning episodes in companion animals and livestock in Europe. The main plant species are described, and the mechanism of action of the primary active agents and their clinical effects are presented. Data reflecting the real incidence of emerging poisoning cases from plant toxins are scarce to nonexistent in most European countries due to a lack of a centralized reporting/poison control system. The diversity of plant species and phytotoxins, as well as the emerging nature of certain plant poisonings, warrant a continuous update of knowledge by veterinarians and animal owners. The taxonomy and active agents present in these plants should be communicated to ensure awareness of the risks these toxins pose for domestic animals.

Inhibition of Tumor Growth and Modulation of Antioxidant Activity of Rhodoxanthin Isolated from Taxus baccata Aril against B16F10 Murine Malignant Melanoma.

Malignant melanoma is the most aggressive type of skin cancer, and due to the numerous limitations of current treatment methods, there is an urgent need to develop novel approaches for both the prevention and treatment of malignant melanoma, with research-oriented bioactive substances representing a notable first step. The current study decided to expand on previous rhodoxanthin research by investigating the possible anti-tumor effect as well as the effect on the antioxidant status in the case of murine melanoma in an experimental model. The 21-day study was carried out on female C57BL/6J mice. On the first day of the experiment, they were subcutaneously inoculated with 106 B16F10 cells and were given rhodoxanthin orally until the end of the study. Rhodoxanthin supplementation significantly reduced tumor growth (42.18%) and weight (15.74%). Furthermore, the epidermal growth factor (EGF) activity was reduced and the concentration of 8-OHdG dropped in the treated melanoma-bearing mice compared to the untreated ones, demonstrating the role of rhodoxanthin in slowing tumor growth, one of the mechanisms being the reduction of EGF level and the decrease of DNA oxidation. The administration of rhodoxanthin determined variations in antioxidant enzymes, both at the plasma level and at the tissue level.

Photodynamic Therapy with Natural Photosensitizers in the Management of Periodontal Disease Induced in Rats.

This study aims to investigate the effect of new natural photosensitizers (PS) (based on oregano essential oil, curcuma extract, and arnica oil) through in vitro cytotoxicity and biological tests in rat-induced periodontal disease, treated with photodynamic therapy (aPDT). The cytotoxicity of PS was performed on human dental pulp mesenchymal stem cells (dMSCs) and human keratinocyte (HaCaT) cell lines. Periodontal disease was induced by ligation of the first mandibular molar of 25 rats, which were divided into 5 groups: control group, periodontitis group, Curcuma and aPDT-treated group, oregano and aPDT-treated group, and aPDT group. The animals were euthanized after 4 weeks of study. Computed tomography imaging has been used to evaluate alveolar bone loss. Hematological and histological evaluation showed a greater magnitude of the inflammatory response and severe destruction of the periodontal ligaments in the untreated group.. For the group with the induced periodontitis and treated with natural photosensitizers, the aPDT improved the results; this therapy could be an important adjuvant treatment. The obtained results of these preliminary studies encourage us to continue the research of periodontitis treated with natural photosensitizers activated by photodynamic therapy.

A novel therapeutic phosphate-based glass improves full-thickness wound healing in a rat model.

Wound healing is a highly dynamic process and innovative therapeutic approaches are currently developed to address challenges of providing optimal wound care. In this study, phosphate-based glasses in the (CuO)x ·(KPO3 )79.5-x ·(ZnO)20 ·(Ag2 O)0.5 system (CuKPO3 ZnAg), with different CuO/ KPO3 ratios were prepared by melt-quenching technique. Constant Cu concentrations were released from the samples during immersion in Simulated Body Fluid (SBF), while Zn concentrations were slightly decreased over time. Glass surface phosphatation leading to formation of Zn crystalline salts was revealed through spectroscopic techniques. This finding was supported by SEM images that illustrated new compound formation. Subsequent cytotoxicity evaluation on HaCaT Keratinocytes using the indirect MTT cell viability assay revealed a CuO concentration-dependent cytotoxicity profile and excellent biocompatibility at low CuO concentrations, in all CuKPO3 ZnAg glasses. Furthermore, the (CuO)5 ·(KPO3 )74.5 ·(ZnO)20 ·(Ag2 O)0.5 sample (5CuKPO3 ZnAg), demonstrated superior antibacterial potency against S. aureus (ATCC 25923) strain compared to amoxicillin and ciprofloxacin. In vivo full-thickness wound healing evaluation showed a significantly higher regenerative effect of the 5CuKPO3 ZnAg sample, in terms of angiogenesis, collagen synthesis and re-epithelialization compared to non-treated wounds. These findings advance our understanding of the therapeutic perspectives of phosphate-based glasses, showing promising potential for wound-healing applications.

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.

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.

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.

New alginate-pullulan-bioactive glass composites with copper oxide for bone tissue regeneration trials.

Composites based on sodium alginate, pullulan, and bioactive SiO2 -CaO-P2 O5 glass-ceramics with copper oxide were prepared as capsules. The obtained samples were structurally characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM), and their bioactivity and biocompatibility properties were also tested both in vitro and in vivo by XRD, FT-IR, SEM, and high-resolution transmission electron microscopy. The fibroblast and osteoblast cell viability assays have shown good proliferation rates for all investigated samples, whereas all composites exhibited a good in vivo tolerance. The recovered composites after 5 weeks' in vivo and in vitro trials evidenced clear macroscopic alterations; particularly, after soaking in simulated body fluid, they have a corn flake aspect, and after their in vivo inoculation, a globular shape is retained. Different crystalline shapes of hydroxyapatite were formed after in vitro and in vivo trials for the glass-ceramic-polymer composites, the in vitro precipitated apatite was found to be nodular, and the in vivo experiment led to needlelike crystallites formation. Histopathological results showed a good biocompatibility with no significant signs of rejection by the host tissue. These assessments performed on the composites indicate that the studied materials can be considered without any doubt suitable candidates for future bone regeneration applications.