Improved quality of life and pain relief in mature horses with osteoarthritis after oral transmucosal cannabidiol oil administration as part of an analgesic regimen.

The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain and quality of life were also assessed using the Horse Chronic Pain Scale (HCPS). The CBD group showed a significant reduction in heart rate, respiratory rate, white blood cell count and oxidative stress (malondialdehyde lipid peroxidation). A significant reduction in HCPS scores was seen in both groups. Lower scores were recorded in the CBD group (3 med; range: 2/4) than in the C group (7 med; range: 4/10). The addition of a cannabidiol-based product to an analgesic protocol was well tolerated and showed positive effects on the treated subjects, improving their quality of life and pain relief.

To Go Where Nature Leads: Focus on Palmitoylethanolamide and Related ALIAmides as Innovative Approach to Neuroinflammatory and Pain-Related Disease States in Honor of Doctor Francesco Della Valle.

Dr [...].

Horse Whole Blood Trace Elements from Different Sicily Areas: Biomonitoring of Environmental Risk.

Horses are excellent bioindicators for the assessment of environmental pollution. The aim of this study was to evaluate the levels and potential bioaccumulation of 28 mineral elements in 75 horse whole blood samples collected from five pollution-prone areas of Sicily, Italy. A direct mercury analyzer (DMA-80) was used for Hg determination, and an inductively coupled plasma mass spectrometer (ICP-MS) for all other elements. A one-way ANOVA test, followed by Bonferroni's multiple comparison for post hoc comparison, was applied to assess statistically significant differences between mineral elements and the five experimental groups. The levels of mineral elements in hay and concentrate were below the limits set by Regulation No. 744/2012. The mineral content of whole blood samples was slightly influenced by the region of origin of the horse. p values < 0.05 were statistically meaningful. However, the concentrations of mineral elements in horses' whole blood remained within reference ranges. In conclusion, the present study shows that the mineral content does not represent a toxicological risk for the analyzed horses. In addition, the study areas did not appear to show a high mineral element contamination.

Mediterranean Plants with Antimicrobial Activity against Staphylococcus aureus, a Meta-Analysis for Green Veterinary Pharmacology Applications.

Antimicrobial resistance (AMR) has emerged as a global health crisis, necessitating the search for innovative strategies to combat infectious diseases. The unique biodiversity of Italian flora offers a treasure trove of plant species and their associated phytochemicals, which hold immense potential as a solution to address AMR. By investigating the antimicrobial properties of Italian flora and their phytochemical constituents, this study aims to shed light on the potential of phyto-complexes as a valuable resource for developing novel or supportive antimicrobial agents useful for animal production.

Modulation of TLR4/NFκB Pathways in Autoimmune Myocarditis.

Myocarditis is an inflammatory and oxidative disorder characterized by immune cell recruitment in the damaged tissue and organ dysfunction. In this paper, we evaluated the molecular pathways involved in myocarditis using a natural compound, Coriolus versicolor, in an experimental model of autoimmune myocarditis (EAM). Animals were immunized with an emulsion of pig cardiac myosin and complete Freund's adjuvant supplemented with mycobacterium tuberculosis; thereafter, Coriolus versicolor (200 mg/Kg) was orally administered for 21 days. At the end of the experiment, blood pressure and heart rate measurements were recorded and the body and heart weights as well. From the molecular point of view, the Coriolus versicolor administration reduced the activation of the TLR4/NF-κB pathway and the levels of pro-inflammatory cytokines (INF-γ, TNF-α, IL-6, IL-17, and IL-2) and restored the levels of anti-inflammatory cytokines (IL-10). These anti-inflammatory effects were accompanied with a reduced lipid peroxidation and nitrite levels and restored the antioxidant enzyme activities (SOD and CAT) and GSH levels. Additionally, it reduced the histological injury and the immune cell recruitment (CD4+ and CD68+ cells). Moreover, we observed an antiapoptotic activity in both intrinsic (Fas/FasL/caspase-3) and extrinsic (Bax/Bcl-2) pathways. Overall, our data showed that Coriolus versicolor administration modulates the TLR4/NF-κB signaling in EAM.

Molecular targets for anti-oxidative protection of açaí berry against diabetes myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion injury (MIRI) is the principal cause of death and occurs after prolonged blockage of the coronary arteries. Diabetes represents one of the main factors aggravating myocardial injury. Restoring blood flow is the first intervention against a heart attack, although reperfusion process could cause additional damage, such as the overproduction of reacting oxygen species (ROS). In recent years, açaí berry has gained international attention as a functional food due to its antioxidant and anti-inflammatory properties; not only that but this fruit has shown glucose-lowering effects. Therefore, this study was designed to evaluate the cardioprotective effects of açaí berry on the inflammatory and oxidative responses associated with diabetic MIRI. Diabetes was induced in rats by a single intravenous inoculation of streptozotocin (60 mg/kg) and allowed to develop for 60 days. MIRI was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. Açaí (200 mg/kg) was administered 5 min before the end of ischemia and 1 h after reperfusion. In this study, we clearly demonstrated that açaí treatment was able to reduce biomarkers of myocardial damage, infarct size, and apoptotic process. Moreover, açaí administrations reduced inflammatory and oxidative response, modulating Nf-kB and Nrf2 pathways. These results suggest that açai berry supplementation could represent a useful strategy for pathological events associated to MIRI.

Current Review of Increasing Animal Health Threat of Per- and Polyfluoroalkyl Substances (PFAS): Harms, Limitations, and Alternatives to Manage Their Toxicity.

Perfluorinated and polyfluorinated alkyl substances (PFAS), more than 4700 in number, are a group of widely used man-made chemicals that accumulate in living things and the environment over time. They are known as "forever chemicals" because they are extremely persistent in our environment and body. Because PFAS have been widely used for many decades, their presence is evident globally, and their persistence and potential toxicity create concern for animals, humans and environmental health. They can have multiple adverse health effects, such as liver damage, thyroid disease, obesity, fertility problems, and cancer. The most significant source of living exposure to PFAS is dietary intake (food and water), but given massive industrial and domestic use, these substances are now punctually present not only domestically but also in the outdoor environment. For example, livestock and wildlife can be exposed to PFAS through contaminated water, soil, substrate, air, or food. In this review, we have analyzed and exposed the characteristics of PFAS and their various uses and reported data on their presence in the environment, from industrialized to less populated areas. In several areas of the planet, even in areas far from large population centers, the presence of PFAS was confirmed, both in marine and terrestrial animals (organisms). Among the most common PFAS identified are undoubtedly perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), two of the most widely used and, to date, among the most studied in terms of toxicokinetics and toxicodynamics. The objective of this review is to provide insights into the toxic potential of PFAS, their exposure, and related mechanisms.

Effect of Pesticide Vinclozolin Toxicity Exposure on Cardiac Oxidative Stress and Myocardial Damage.

(1) Background: Vinclozolin is a popular fungicide used in fruit, ornamental plants, and vegetable crops. It has recently been seen that prolonged exposure to VZN can cause human or animal health damage to various organs, but little is known to date about its cardiovascular effects. In this study, we addressed the chronic effects of VZN on the myocardium and the enzymes involved in the cardiovascular function. (2) Methods: The animals were divided into four groups: group 1 served as the control, group 2 received 1 mg/kg of VZN by gavage, group 3 received 30 mg/kg of VZN by gavage, and group 4 received 100 mg/kg of VZN by gavage, for 30 days. (3) Results: Results showed that 100 mg/kg VZN markedly increased the plasma concentration of cardiac markers (CK-MB, cTnT, ANP, BNP). Moreover, compared to the control group, VZN treatment decreased the activity of SOD, CAT, and GPx, and downregulated the mRNA expression levels of Nrf2. Furthermore, collagen deposition was amplified owing to 100 mg/kg VZN cardiotoxicity. This harmful effect was confirmed by a histological study using hematoxylin and eosin (H&E) and Masson's trichrome staining. (4) Conclusion: Overall, our results proved the cardiotoxicity caused by chronic exposure to VZN.

Inhibiting IL-6 in medicine: a new twist to sustain inhibition of his cytokine tin the therapy of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease characterized by an increase in blood pressure in the lungs' arteries. It can occur in a variety of species, including humans, dogs, cats, and horses. To date, PAH has a high mortality rate in both veterinary and human medicine, often due to complications such as heart failure. The complex pathological mechanisms of PAH involve multiple cellular signalling pathways at various levels. IL-6 is a powerful pleiotropic cytokine that regulates several phases of immune response, inflammation, and tissue remodelling. The hypothesis of this study was that the use of an IL-6 antagonist in PAH could interrupt or mitigate the cascade of events that leads to the progression of the disease and the worsening of clinical outcome, as well as tissue remodelling. In this study, we used two pharmacological protocols with an IL-6 receptor antagonist in a monocrotaline-induced PAH model in rats. Our results showed that the use of an IL-6 receptor antagonist had a significant protective effect, ameliorating both haemodynamic parameters, lung and cardiac function, tissue remodelling, and the inflammation associated with PAH. The results of this study suggest that the inhibition IL-6 could be a useful pharmacological strategy in PAH, in both human and veterinary medicine.

Cytoprotective and Antioxidant Effects of Hydrolysates from Black Soldier Fly (Hermetia illucens).

The black soldier fly (BSF), Hermetia illucens, has been recognized as one of the most promising insect species for its ability to valorize organic waste while producing a valuable larval biomass with a great potential as a sustainable source of nutrients, including proteins and bioactive molecules. In the present study, BSF larvae were used to produce and characterize the protein hydrolysates (BPHs) that were then evaluated for their potential biological activity in vitro. The BPHs obtained from the BSF larvae proteins by enzymatic digestion were characterized by Nuclear Magnetic Resonance (NMR) and polyacrylamide gel electrophoresis and assessed for their antioxidant activity (BPHs in the range of 0.1 to 1.5 mg/mL) in L-929 cells. Our findings show that BPHs can exert a dose-dependent cytoprotective role against H2O2-iduced oxidative stress in cells. This antioxidant activity relies on the reduction of ROS levels in challenged cells as measured by flow cytometry and fluorescence microscopy, together with the induction and nuclear translocation of Nrf2, as evaluated by qPCR and indirect immunofluorescence analysis, respectively. Overall, our findings on the remarkable biological activity of the BPHs obtained in a large-scale process strongly suggest the application of BPHs as ingredients promoting animal health in feed formulations.

Uroprotective and pain-relieving effect of dietary supplementation with micronized palmitoyl-glucosamine and hesperidin in a chronic model of cyclophosphamide-induced cystitis.

Introduction: Feline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations. Methods: The current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug. Results: Higher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson's trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine. Discussion: PGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis.

Correction: D'Amico et al. Consumption of Cashew (Anacardium occidentale L.) Nuts Counteracts Oxidative Stress and Tissue Inflammation in Mild Hyperhomocysteinemia in Rats. Nutrients 2022, 14, 1474.

In the original publication [...].

Intratesticular Versus Intrafunicular Lidocaine to Reduce Perioperative Nociception and Immunological Response in Ponies Undergoing Field Castration.

The aim of this study was to evaluate the impact of intratesticular or intrafunicular lidocaine to reduce perioperative nociception and cytokine release in ponies undergoing field castration under total intravenous anaesthesia. Before castration, one group was injected with intrafunicular (FL) lidocaine and the other received intratesticular (TL) lidocaine. All ponies were premedicated with acepromazine (0.05 mg/kg) intramuscularly. Twenty minutes after the administration of acepromazine, xylazine (1 mg/kg) and butorphanol (0.02 mg/kg) were administered intravenously. Lidocaine 2% was given 1 mL/100 kg intrafunicularly in the FL groups or 2 mL/100 kg intratesticularly on each testicular side for TL. Surgery was performed by the same team of two experienced surgeons using Serra's emasculator and an open technique was used for all ponies in order to promote postoperative drainage. In this study, we focused on the plasmatic levels of TNF-α and IL-6. The results from this study showed a significant difference in plasmatic concentrations of TNF-α and IL-6 between the two different locoregional anaesthetic protocols. Taken together, the results suggest that the intrafunicular lidocaine locoregional anaesthesia could be a useful technique in the anaesthesia protocol for field pony castration.

Early Exposure to Environmental Pollutants: Imidacloprid Potentiates Cadmium Toxicity on Zebrafish Retinal Cells Death.

In the present study, we analyzed the combination of non-toxic concentrations per se, of Cd and a pesticide the imidacloprid (IMI) (10 and 50 µM for Cd and 195 µM for IMI), to highlight early developmental toxicity and possible damage to retinal cells. Co-exposure to Cd and IMI showed a toxic effect in zebrafish larval development, with lowered degrees of survival and hatching, and in some cases the induction of structural alterations and edema. In addition, co-exposure to 50 and 195 µM, respectively, for Cd and IMI, also showed increased apoptosis in eye cells, accompanied by up regulation of genes associated with antioxidant markers (cat, sod1, nrf2 and ho-1). Thus, the present study aims to highlight how the presence of multiple contaminants, even at low concentrations, can be a risk factor in a model of zebrafish (Danio rerio). The presence of other contaminants, such as IMI, can cause an enhancement of the toxic action of Cd on morphological changes in the early life stage of zebrafish, but more importantly disrupt the normal development of the retina, eventually triggering apoptosis.

Açai Berry Attenuates Cyclophosphamide-Induced Damage in Genitourinary Axis-Modulating Nrf-2/HO-1 Pathways.

Cyclophosphamide (CYP) is used to treat different malignancies and autoimmune disorders in men. This chemotherapy frequently reduces tumors, which is beneficial, but also causes infertility because of severe oxidative stress, inflammation, and apoptosis in the bladder and testes brought on by its metabolite, acrolein. The goal of this study was to assess the efficacy of a novel food, açai berry, in preventing CYP-induced damage in the bladder and testes. METHODS: CYP was administered intraperitoneally once during the experiment at a dose of 200 mg/kg body weight diluted in 10 mL/kg b.w. of water. Açai berry was administered orally at a dose of 500 mg/kg. RESULTS: The administration of açai berry was able to reduce inflammation, oxidative stress, lipid peroxidation, apoptosis, and histological changes in the bladder and testes after CYP injection. CONCLUSIONS: Our findings show for the first time that açai berry modulates physiological antioxidant defenses to protect the bladder and testes against CYP-induced changes.

Complex Interplay between Autophagy and Oxidative Stress in the Development of Endometriosis.

Endometriosis (Endo) is a chronic gynecological disease. This paper aimed to evaluate the modulation of autophagy, oxidative stress and apoptosis with Açai Berries in a rat model of endometriosis. Endometriosis was induced with an intraperitoneal injection of minced uterus tissue from a donor rat into a recipient one. The abdominal high-frequency ultrasound (hfUS) analysis was performed at 7 and 14 days from the endometriosis induction to evaluate the growth of the lesion during the experiment. Seven days from the induction, once the lesions were implanted, an Açai Berry was administered daily by gavage for the next seven days. At the end of the experiment, the hfUS analysis showed a reduced lesion diameter in animals given the Açai Berry. A macroscopical and histological analysis confirmed this result. From the molecular point of view, Western blot analyses were conducted to evaluate the autophagy induction. Samples collected from the Endo group showed impaired autophagy, while the Açai Berry administration inhibited PI3K and AKT and ERK1/2 phosphorylation and promoted autophagy by inactivating mTOR. Additionally, Açai Berry administration dephosphorylated ATG1, promoting the activity of the ATG1/ULK1 complex that recruited Ambra1/Beclin1 and Atg9 to promote autophagosome nucleation and LC3II expression. Açai Berry administration also restored mitophagy, which increased Parkin cytosolic expression. The Açai Berry increased the expression of NRF2 in the nucleus and the expression of its downstream antioxidant proteins as NQO-1 and HO-1, thereby restoring the oxidative imbalance. It also restored the impaired apoptotic pathway by reducing BCL-2 and increasing BAX expression. This result was also confirmed by the TUNEL assay. Overall, our results displayed that Açai Berry administration was able to modulate autophagy, oxidative stress and apoptosis during endometriosis.

Regulation of Apoptosis and Oxidative Stress by Oral Boswellia Serrata Gum Resin Extract in a Rat Model of Endometriosis.

Endometriosis (EMS) is a gynecological disease characterized by inflammation, oxidative stress, and apoptosis dysregulation. This study aims to evaluate the effect of Boswellia serrata gum resin extract (BS) on the endometriotic lesions in a rat model of endometriosis. We divided female rats into three groups, including Sham, EMS, EMS + BS. In the EMS and EMS + BS groups, pathology was induced and after 7 days by the abdominal high-frequency ultrasound (hfUS) analysis the presence of the endometriotic lesions was confirmed. Subsequently, the EMS + BS group was administered with BS (100 mg/Kg) daily for another 7 days. At the end of the experiment, the hfUS analysis was repeated and the animals were sacrificed to evaluate the size and histoarchitecture of the endometriotic implants. Pelvic ultrasound showed increased size of the endometriotic lesions in the Endo group, while BS administration reduced the lesion size. The macroscopic analysis confirmed the reduced area and volume of the endometriotic lesions of the EMS + BS group. The histological analysis showed reduced characteristic of ectopic stroma and glands in the animals treated with BS. Western blot analyses were conducted to evaluate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. BS increases the expression of Nfr2 in the nucleus and the expression of its downstream antioxidant proteins NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. BS administration also restored the impaired apoptotic pathway in the lesions by reducing Bcl-2 expression and increasing Bax and cleaved caspase 9 levels. The BS apoptotic effect was also confirmed by the cleavage of PARP, another specific marker of apoptosis, and by the TUNEL assay. Our results show that BS administration resulted in an effective and coordinated suppression of Endo owing to its antioxidant and antiapoptotic activities.

Modulation of NRF-2 Pathway Contributes to the Therapeutic Effects of Boswellia serrata Gum Resin Extract in a Model of Experimental Autoimmune Myocarditis.

Myocarditis is a clinically dangerous disease that can result in death. Oxidative stress as well as inflammatory and immune responses play important roles in the development of myocarditis. Presently, more research has been carried out on anti-inflammatory treatment using natural compounds. The aim was to evaluate the anti-inflammatory and antioxidant effect of Boswellia gum resin extract in an experimental autoimmune myocarditis (EAM) and the involvement of molecular pathways. Rats were immunized with porcine cardiac myosin to ascertain EAM. The EAM rats were treated orally with Boswellia extract or vehicle for 21 days. EAM caused macroscopic and microscopic alterations with necrosis, inflammatory cell infiltration, fibrosis of the heart tissues, as well as clinical biochemical changes, cytokines release, altered immune response, and oxidative stress. Oral treatment with Boswellia markedly reduced myocardial damage, decreased inflammatory infiltrate, fibrosis, biochemical markers, such as lactate dehydrogenase and the creatine kinase, and heart weight/body weight ratio. In addition, low nitric oxide and malondialdehyde levels together with the upregulation of antioxidant nuclear factor erythroid 2-related factor 2 NRF-2 pathway were observed in EAM rats treated with Boswellia. Thus, Boswellia could be considered as a new natural extract to combat heart pathologies, such as autoimmune myocarditis.

Natural Compounds Such as Hericium erinaceus and Coriolus versicolor Modulate Neuroinflammation, Oxidative Stress and Lipoxin A4 Expression in Rotenone-Induced Parkinson's Disease in Mice.

BACKGROUND: A growing body of research suggests that oxidative stress and neuroinflammation are early pathogenic features of neurodegenerative disorders. In recent years, the vitagene system has emerged as a potential target, as it has been shown to have a high neuroprotective power. Therefore, the discovery of molecules capable of activating this system may represent a new therapeutic target to limit the deleterious consequences induced by oxidative stress and neuroinflammation, such as neurodegeneration. Lipoxins are derived from arachidonic acid, and their role in the resolution of systemic inflammation is well established; however, they have become increasingly involved in the regulation of neuroinflammatory and neurodegenerative processes. Our study aimed at activating the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) redox system and increasing lipoxin A4 for the modulation of antioxidant stress and neuroinflammation through the action of two fungi in a rotenone-induced Parkinson's model. METHODS: During the experiment, mice received Hericium erinaceus, Coriolus versicolor or a combination of the two (200 mg/kg, orally) concomitantly with rotenone (5 mg/kg, orally) for 28 days. RESULTS: The results obtained highlighted the ability of these two fungi and, in particular, their ability through their association to act on neuroinflammation through the nuclear factor-kB pathway and on oxidative stress through the Nrf2 pathway. This prevented dopaminergic neurons from undergoing apoptosis and prevented the alteration of typical Parkinson's disease (PD) markers and α-synuclein accumulation. The action of Hericium erinaceus and Coriolus versicolor was also able to limit the motor and non-motor alterations characteristic of PD. CONCLUSIONS: Since these two mushrooms are subject to fewer regulations than traditional drugs, they could represent a promising nutraceutical choice for preventing PD.