Multidisciplinary, General Pharmacology, Toxicology and Pharmaceutics, Veterinary, Pharmacology, Toxicology and Pharmaceutics
183
Scopus Publications
Scopus Publications
One Health perspectives on veterinary residues and bioaccumulation in marine mussels Gianluca Antonio Franco, Roberta Fusco, Enrico Gugliandolo, Marika Cordaro, Davide Di Paola Marine Environmental Research, 2026 The increase in pharmaceutical residues and environmental contaminants, including heavy metals and biotoxins, in coastal ecosystems represents a critical threat to global health. Mussels (Mytilus spp.), as sessile filter feeders, serve as primary bioaccumulators and biological indicators of this chemical pressure, yet their toxicological role in human health is often underestimated. This review explores the physiological and toxicological effects of the accumulation of complex contaminants and pharmaceutical residues, specifically including veterinary drugs that reach the marine environment through livestock runoff and aquaculture practices. Mussels' reduced metabolic capacity, combined with the interference of multixenobiotic resistance (MXR) efflux systems, leads to the prolonged accumulation of these substances within their tissues. Particular attention is given to mixture toxicity and the role of microplastics as vectors that amplify the bioavailability of contaminants, triggering significant oxidative stress and epigenetic alterations that compromise the reproduction and resilience of the mollusk. The implications for public health involve the potential facilitation of antimicrobial resistance (AMR), driven by the bioaccumulation of both human and veterinary antibiotics. dietary exposure to chemical residues; however, the actual risk of poisoning depends on whether tissue concentrations exceed established regulatory safety thresholds. Due to their high filtration capacity, mussels act as ecological hotspots, facilitating the transfer of pharmaceuticals and their metabolites into the food chain. We conclude that effective risk management requires a proactive approach at the source. The urgent integration of surveillance protocols with molecular ecotoxicology, alongside the adoption of advanced technological solutions, such as tertiary wastewater treatment and the monitoring of watersheds adjacent to livestock farming areas, are essential to harmonize residue limits and ensure food security and the sustainability of marine resources for future generations.
Protective effect of snail secretion filtrate in an in vitro model of mastitis Gianluca Antonio Franco, Ylenia Marino, Rosalia Crupi, Davide di Paola, Salvatore Cuzzocrea, Enrico Gugliandolo Veterinary Record Open, 2026 Background Bovine mastitis is inflammation of the mammary gland mainly caused by bacterial infections, with relevant economic costs and implications related to antibiotic resistance. In light of the increasing demand for sustainable therapies, this study evaluated the anti‐inflammatory and antioxidant effects of snail secretion filtrate (SSF) from the species Helix Aspersa Muller in an in vitro model of bovine mastitis. Methods Bovine mammary cells (MAC‐T) stimulated with lipopolysaccharide (LPS) were used to induce the inflammatory process. The cells were then treated with SSF to analyse its effects on oxidative stress, production of inflammatory cytokines (tumour necrosis factor‐α, interleukin‐6 and interleukin‐1β), expression of enzymes associated with inflammation such as inducible nitric oxide (iNOS) and cyclo‐oxygenase‐2 (COX‐2) and cytoprotection as heme‐oxygenase 1 (HO‐1). Results Snail secretion filtrate significantly reduced the levels of reactive oxygen species and the production of pro‐inflammatory cytokines induced by LPS. Furthermore, it positively modulated the expression of iNOS and COX‐2, reducing their levels and increasing the expression of HO‐1, suggesting a cytoprotective action. Conclusions Snail secretion filtrate was effective in reducing inflammation and oxidative stress in an in vitro model of bovine mastitis. The results suggest the potential use of SSF as a natural and sustainable remedy, in line with the One Health approach.
Modulation of the endocannabinoid system reduces inflammatory signalling in canine mammary carcinoma cells Gianluca Antonio Franco, Ylenia Marino, Claudia Rifici, Roberta Fusco, Davide di Paola, Salvatore Cuzzocrea, Giuseppe Catone, Cecilia Vullo, Enrico Gugliandolo Veterinary Record Open, 2026 Background Canine mammary carcinoma (CMC) is characterised by a chronic inflammatory microenvironment resembling human breast cancer; however, the upstream regulatory mechanisms driving this phenotype remain unclear. The endocannabinoid system (ECS) has emerged as a potential modulator of inflammation and tumour biology. This study investigated the role of the ECS in CMC and evaluated the anti‐inflammatory effects of cannabidiol (CBD). Methods Primary cell cultures were established from surgically excised CMC tissues, with matched normal mammary epithelium used as controls. Basal mRNA expression of ECS‐related receptors (CB1, CB2, transient receptor potential vanilloid 1 [TRPV1], G‐protein‐coupled receptor 55 [GPR55] and peroxisome proliferator‐activated receptor alpha [PPAR‐α]) and inflammatory mediators (COX‐1, COX‐2, interleukin [IL]‐4, IL‐6, IL‐33, IL‐17A, tumour necrosis factor‐alpha [TNF‐α] and LCN2) was assessed by reverse transcription quantitative polymerase chain reaction. Cytokine secretion (IL‐6, IL‐8, TNF‐α and IL‐17A) was quantified by enzyme‐linked immunosorbent assay. Cell viability assays were performed to determine the 24‐h IC 50 of CBD (32 µM), and sub‐cytotoxic concentrations (3, 10 and 20 µM) were subsequently applied for 24 h. Results Canine mammary carcinoma‐derived cells exhibited significant overexpression of ECS receptors (CB1, CB2, TRPV1, GPR55 and PPAR‐α) compared to normal controls. These cells also showed increased secretion of pro‐inflammatory cytokines, including IL‐6, IL‐8, TNF‐α and IL‐17A. Treatment with CBD at 10–20 µM significantly downregulated key inflammatory genes, particularly COX‐2, IL‐6 and TNF‐α, and reduced corresponding cytokine release without compromising cell viability. Conclusion The ECS is upregulated in CMC and appears to contribute to the inflammatory tumour microenvironment. Cannabidiol effectively attenuates this inflammatory phenotype at sub‐cytotoxic concentrations, supporting its potential as a therapeutic agent in CMC.
Mussels as integrative sentinels of emerging contaminants in aquatic ecosystems Nicla Tranchida, Roberta Fusco, Enrico Gugliandolo, Marika Cordaro, Davide Di Paola Pesticide Biochemistry and Physiology, 2026 Emerging pollutants (EPs), including emerging contaminants (ECs) such as pharmaceuticals andpersonal care products, alongside with microplastics are increasingly causing world water quality concerns. Their typically low concentrations and irregular discharge patterns complicate monitoring efforts, and traditional chemical analyses are often insufficient to fully assess their biological relevance. In this context, biomonitoring-using living organisms to detect and quantify environmental contaminants-provides an essential complementary approach. Mussels represent one of the most effective bioindicator species in aquatic environments. Their sessile lifestyle, filter-feeding activity, and widespread distribution enable them to efficiently accumulate contaminants directly from the water column, thereby providing an integrated record of pollutant exposure over time. As a result, mussel-based biomonitoring offers ecologically meaningful insights into the presence and biological effects of emerging contaminants, contributing to more sustainable water-quality management strategies. The aim of this review is to summarize recent advances and future perspectives on the use of mussels as monitors of emerging contaminants. We address the physiological foundations supporting their reliability-including filtration processes, bioaccumulation mechanisms, and their role as "sentinel species." Furthermore, we examine the major classes of contaminants detected in mussel tissues, ranging from pharmaceuticals to plastic polymers. Finally, the review evaluates the latest findings in the field, while also critically discussing the limitations and challenges associated with mussel-based biomonitoring.
Environmental Mycotoxins and Brain Health: Protective Role of Bromelain Against Fumonisin B1 in SH-SY5Y Cells Gianluca Antonio Franco, Francesca Inferrera, Nicla Tranchida, Davide Di Paola, Roberta Fusco, Salvatore Cuzzocrea, Enrico Gugliandolo Environmental Toxicology, 2026 Fumonisin B1 (FB1), a mycotoxin commonly found in contaminated food and feed, has been increasingly implicated in neurotoxicity, although its mechanisms remain poorly understood. This study investigates the neurotoxic potential of FB1 in human SH‐SY5Y neuroblastoma cells, both undifferentiated and RA‐differentiated, and evaluates the protective effect of bromelain, a natural proteolytic enzyme with antioxidant and anti‐inflammatory properties. Cells were exposed to 50 μM FB1 for 24 h, with or without co‐treatment with bromelain (10 or 50 μg/mL). FB1 significantly reduced cell viability and triggered reactive oxygen species (ROS) production, mitochondrial membrane depolarization, lipid peroxidation, inflammatory cytokine release (IL‐6 and TNF‐α), and apoptosis, particularly in differentiated cells. Bromelain co‐treatment attenuated these effects in a dose‐dependent manner, preserving mitochondrial function, reducing oxidative and inflammatory markers, and lowering apoptotic cell death. These findings emphasize the neurotoxic risk posed by FB1 and highlight bromelain as a promising multi‐target protective agent. Identifying effective countermeasures against environmental neurotoxins is crucial for public health and disease prevention.
Ecotoxicological Insights From Ex Vivo Exposure of Whole Blood to PFOS and Glyphosate: Oxidative Stress and Immune Disruption Francesco Molinari, Gianluca Antonio Franco, Francesca Inferrera, Nicla Tranchida, Antonella Iaconis, Maria Rizzo, Giuseppe Piccione, Enrico Gugliandolo, Davide Di Paola Environmental Toxicology, 2026 This study investigated the immunomodulatory effects of PFOS and glyphosate (GLY), both individually and in combination, on the whole blood of three ruminant species (cow, goats, and sheep) exposed ex vivo to environmentally relevant concentrations. The research focused on key biomarkers of oxidative stress (MDA), inflammation (myeloperoxidase activity, nitrite production), and immune function (TNFα and IL‐6 cytokine production, both at baseline and following LPS stimulation). Results indicated species‐specific differences in oxidative stress response, with sheep and goats showing higher MDA levels under combined PFOS and GLY exposure. Furthermore, co‐exposure exacerbated inflammatory responses (MDA activity and NO2‐ production) in LPS‐stimulated sheep and goats. Critically, a synergistic effect of PFOS and GLY co‐exposure significantly increased both TNFα and IL‐6 production across all species, even without LPS stimulation, suggesting a heightened pro‐inflammatory state. These findings raise concerns about the potential of these contaminants to disrupt immune homeostasis in grazing animals, impacting their health, productivity, and disease resistance, and potentially posing risks to human health through food chain contamination. The study highlights the need for further research to elucidate the underlying molecular mechanisms and assess the long‐term effects of chronic exposure to these contaminants on animal health and potential human health risks.
Composition of allogeneic equine orthobiologics and their repeated intra-articular administrations Yanne Van Reusel, Sarah Y. Broeckx, Anna Carolo, Marco Patruno, Jonas Steenbrugge, Jimmy Saunders, Enrico Gugliandolo, Jan H. Spaas Equine Veterinary Journal, 2026 Background Orthobiologics such as platelet‐rich plasma (PRP) and alpha‐2‐macroglobulin (A2MG) are increasingly used for equine musculoskeletal injuries. However, their composition and safety with repeated allogeneic intra‐articular administration remain poorly investigated. Objectives To characterise orthobiological preparations with or without 1 h incubation at 37°C (PRP, PRP + Inc, A2MG, A2MG + Inc) and evaluate immunological safety following repeated intra‐articular administration (autologous and allogeneic) of PRP combined with A2MG + Inc in healthy horses. Study Design In vivo experiments. Methods This was a two‐phase study with biochemical characterisation followed by repeated intra‐articular injections in four healthy horses. Blood was processed to produce PRP or A2MG, with or without incubation, and characterised using haematology, biochemistry and enzyme‐linked immunosorbent assay. For immunogenic assessment, healthy horses received three intra‐articular injections of combined PRP and A2MG + Inc at 2‐week intervals (Days 0, 14 and 28) (allogeneic n = 3, autologous n = 1). Blood and synovial fluid were collected on Days 0, 14, 28 and 42. Blood was analysed for haematology, biochemistry, CD4/CD8 ratio and SAA, while synovial fluid was analysed for leukocyte counts and immunoglobulins. Results Biochemical characterisation demonstrated effective removal of blood cells from all orthobiologics. PRP‐based formulations were enriched in platelets and growth factors, whereas A2MG preparations had higher alpha‐2‐macroglobulin and lower growth factor levels. Repeated intra‐articular administration of PRP and A2MG + Inc caused no clinically relevant changes in systemic or synovial immune cells, lymphocyte subsets, or acute‐phase markers, indicating no immunological activation. Main Limitations Small sample sizes, the limited scope of characterised compositions and the use of combined PRP and A2MG + Inc for which only individual components were characterised. Conclusions PRP may promote repair via growth factors, and A2MG is proposed to modulate immunity and catabolism. Repeated intra‐articular injections of PRP with A2MG + Inc caused no systemic or synovial immune response, with no differences between autologous and allogeneic use.
Antibiotic and Heavy Metal Resistance in Marine Bacteria from Terra Nova Bay (Ross Sea): Insights from Wild Fish and Environmental Samples Enrico Gugliandolo, Bilal Mghili, Francesca Fabrizi, Kannan Gunasekaran, Francesco Smedile, Francesca Inferrera, Sabrina Natale, Teresa Romeo, Erika Arcadi, Syed Sikandar Habib, Maurizio Azzaro, Teresa Bottari, Monique Mancuso Animals, 2026 This study examines the occurrence of bacteria resistant to antibiotics and heavy metals in Terra Nova Bay, a coastal area of the Ross Sea in Antarctica that is increasingly recognised as vulnerable to human influence. During the 37th Italian Antarctic Expedition (2021–2022), researchers collected seawater, sediment, and fish samples from the notothenioid species Trematomus bernacchii to evaluate microbial resistance in an environment once considered largely pristine. Fifty heterotrophic bacterial isolates were obtained and tested against twenty-eight antibiotics, revealing a notable presence of multidrug resistance. These multidrug-resistant isolates were then assessed for their tolerance to eight heavy metal salts to understand whether resistance traits extended beyond antimicrobials. Twelve isolates showing resistance to both antibiotics and metals were selected for further genetic screening, targeting key resistance genes linked to tetracycline, vancomycin, sulphonamides, and other antimicrobial classes. The detection of multiple resistance genes in genera such as Pseudomonas, Pseudoalteromonas, and Psychrobacter indicates that both natural selective pressures and local, human-related contamination may be shaping resistance patterns in this region. Overall, the study demonstrates that even remote Antarctic marine ecosystems can host bacteria with complex resistance profiles. While these ecosystems are largely isolated, human activities such as scientific research, tourism, and the introduction of pollutants may contribute to the dissemination of antibiotic resistance genes, raising important ecological and potential public health considerations regarding the spread of resistance in polar environments.
Management of acute lung injury: Palmitoylethanolamide as a new approach Alessio Filippo Peritore, Ramona D’Amico, Rosalba Siracusa, Marika Cordaro, Roberta Fusco, Enrico Gugliandolo, Tiziana Genovese, Rosalia Crupi, Rosanna Di Paola, Salvatore Cuzzocrea, Daniela Impellizzeri International Journal of Molecular Sciences, 2021
Autophagy and mitophagy promotion in a rat model of endometriosis Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Marika Cordaro, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Angela Trovato Salinaro, Emanuela Raffone, Tiziana Genovese, Salvatore Cuzzocrea, Roberta Fusco, Rosanna Di Paola International Journal of Molecular Sciences, 2021
