Oxidative stress and mitochondrial dysfunction in brain of vinclozolin exposed animals.

Vinclozolin (VCZ) is a widely used fungicide in agriculture, especially in fruits and wine. Various studies have detailed the effects of VCZ exposure on different organs, but no information is available on its effects on brain tissues. This paper investigated the effects of VCZ exposure on the oxidative stress and mitochondrial dysfunction in brain tissue. C57BL/6 mice were exposed to VCZ (100 mg/kg) by oral gavage for 28 days. Mitochondrial homeostasis, often known as mitochondrial quality control, involves a range of processes, including mitochondrial biogenesis, mitochondrial fusion and fission, mitophagy and autophagy. VCZ administration modified the mRNA expression levels of Sirt1, Sirt3, PGC-1α, TFAM, Nrf1, VDAC-1 and Cyt c in brain tissue, as compared to control animals (CTR). The analyses also showed increased oxidative stress, in particular VCZ administration reduced SOD and CAT activities and GSH levels while increased T-AOC levels and lipid peroxidation. Additionally, brain tissues from VCZ group showed DNA oxidation (increased PARP-1 immunostaining) and apoptosis (increased TUNEL+ cells, increased expression of Bax mRNA level and reduced Bcl-2 levels). Western blot and immunohistochemical analyses showed increased mitophagic pathway with the accumulation of PINK1 and Parkin in mitochondria. Additionally, autophagic pathway was also increased with the increased expression and colocalization of LC3 with Neun and GFAP. Overall, this study showed that chronic VCZ exposure impaired mitochondrial homeostasis and increased oxidative stress in brain tissues.

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.

Bioactive Compounds of the Mediterranean Diet as Nutritional Support to Fight Neurodegenerative Disease.

Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress, and neuronal depletion. They include selective malfunction and progressive loss of neurons, glial cells, and neural networks in the brain and spinal cord. There is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases because, today, there is no treatment that can cure degenerative diseases; however, we have many symptomatic treatments. Current nutritional approaches are beginning to reflect a fundamental change in our understanding of health. The Mediterranean diet may have a protective effect on the neurodegenerative process because it is rich in antioxidants, fiber, and omega-3 polyunsaturated fatty acids. Increasing knowledge regarding the impact of diet on regulation at the genetic and molecular levels is changing the way we consider the role of nutrition, resulting in new dietary strategies. Natural products, thanks to their bioactive compounds, have recently undergone extensive exploration and study for their therapeutic potential for a variety of diseases. Targeting simultaneous multiple mechanisms of action and a neuroprotection approach with the diet could prevent cell death and restore function to damaged neurons. For these reasons, this review will be focused on the therapeutic potential of natural products and the associations between the Mediterranean-style diet (MD), neurodegenerative diseases, and markers and mechanisms of neurodegeneration.

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.

Açai Berry Administration Promotes Wound Healing through Wnt/ß-Catenin Pathway.

Recently, wound healing has received increased attention from both a scientific and clinical point of view. It is characterized by an organized series of processes: angiogenesis, cell migration and proliferation, extracellular matrix production, and remodeling. Many of these processes are controlled by the Wnt pathway, which activates them. The aim of the study was to evaluate the molecular mechanism of açai berry administration in a mouse model of wound healing. CD1 male mice were used in this research. Two full-thickness excisional wounds (5 mm) were performed with a sterile biopsy punch on the dorsum to create two circular, full-thickness skin wounds on either side of the median line on the dorsum. Açai berry was administered by oral administration (500 mg/kg dissolved in saline) for 6 days after induction of the wound. Our study demonstrated that açai berry can modulate the Wnt pathway, reducing the expression of Wnt3a, the cysteine-rich domain of frizzled (FZ)8, and the accumulation of cytosolic and nuclear ß-catenin. Moreover, açai berry reduced the levels of TNF-α and IL-18, which are target genes strictly downstream of the Wnt/ß-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NF-κB pathway. Furthermore, Wnt can modulate the activity of growth factors, such as TGF-ß, and VEGF, which are the basis of the wound-healing process. In conclusion, we can confirm that açai berry can modulate the activity of the Wnt/ß-catenin pathway, as it is involved in the inflammatory process and in the activity of the growth factor implicated in wound healing.

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.

Environmental Toxicity Assessment of Sodium Fluoride and Platinum-Derived Drugs Co-Exposure on Aquatic Organisms.

Pharmaceuticals are widely acknowledged to be a threat to aquatic life. Over the last two decades, the steady use of biologically active chemicals for human health has been mirrored by a rise in the leaking of these chemicals into natural environments. The aim of this work was to detect the toxicity of sodium fluoride (NaF) exposure and platinum-derived drugs in an ecological setting on aquatic organism development. From 24 to 96 h post-fertilization, zebrafish embryos were treated to dosages of NaF 10 mg/L-1 + cisplatin (CDDP) 100 µM, one with NaF 10 mg/L-1 + carboplatin (CARP) 25 µM, one with NaF 10 mg/L-1 + CDDP 100 µM + CARP 25 µM. Fluoride exposure in combination with Cisplatin and Carboplatin (non-toxic concentration) had an effect on survival and hatching rate according to this study. Additionally, it significantly disturbed the antioxidant defense system and increased ROS in zebrafish larvae. NaF 10 mg/L-1 associated with CDDP 100 µM and CARP 25 µM, increased the production of apoptosis-related proteins (caspase 3, bax, and bcl-2) and the downregulation of acetylcholinesterase (AChE) activity, while no effect was seen for the single exposure.