Ultramicroscopic organization of the exterior olfactory organ in Anguilla vulgaris in relation to its spawning migration.

Background: Catadromous fishes have well-developed elongated olfactory organs with numerous lamellae and different types of receptor neurons related to their breeding migration. Aim: The current study showed how the olfactory system adapted to the catadromous life. Our work declared the need of the migratory fishes for the sense of smell that is exhibited by a higher number of the olfactory lamellae and the receptor neuron verification in the olfactory epithelium. Methods: Ten specimens of fully grown, but pre-matured, silver eels of Anguilla vulgaris were captured at the outlet of Edco Lake, overlooking the Mediterranean Sea, east of Alexandria. Olfactory rosettes were dissected and fixed for scanning electron microscope (SEM) and transmission electron microscope (TEM). Results: Our study gave a morphological description of the olfactory system of A. vulgaris. At the ultrastructural level using SEM and TEM, one olfactory rosette was provided with 90-100 flat radial olfactory lamellae. The nasal configuration allowed water to enter and exit, transferring odorant molecules to olfactory receptor cells which comprise long cylindrical ciliated and microvillous receptors as well as rod-tipped cells. These cells are bipolar neurons with upward dendritic knobs. The olfactory epithelia also include crypt receptor cells. Interestingly, the olfactory neurons are delimited by nonsensory supporting cells, including long motile kinocilia and sustentacular supporting cells beside mucus secretory goblet cells and ionocytes or labyrinth cells that contribute to the olfaction process. Conclusion: Olfaction is crucial in all vertebrates, including fishes as it involves reproduction, parental, feeding, defensive, schooling, and migration behaviors. Here, A. vulgaris is an excellent model for catadromous fishes. It has a well-developed olfactory organ to cope with the dramatic climate change, habitat loss, water pollution, and altered ocean currents effect during their catadromous life for reproduction.

Zinc Oxide Nanoparticles (ZnO-NPs) Induce Cytotoxicity in the Zebrafish Olfactory Organs via Activating Oxidative Stress and Apoptosis at the Ultrastructure and Genetic Levels.

Nanotechnology has gained tremendous attention because of its crucial characteristics and wide biomedical applications. Although zinc oxide nanoparticles (ZnO-NPs) are involved in many industrial applications, researchers pay more attention to their toxic effects on living organisms. Since the olfactory epithelium is exposed to the external environment, it is considered the first organ affected by ZnO-NPs. Herein, we demonstrated the cytotoxic effect of ZnO-NPs on the olfactory organ of adult zebrafish after 60 days post-treatment. We opted for this period when fishes stop eating their diet from the aquarium, appear feeble, and cannot swim freely. Our study demonstrated that ZnO-NPs induced significant malformations of the olfactory rosettes at histological, ultrastructural, and genetic levels. At the ultrastructure level, the olfactory lamellae appeared collapsed, malformed, and twisted with signs of degeneration and loss of intercellular connections. In addition, ZnO-NPs harmed sensory receptor and ciliated cells, microvilli, rodlet, crypt, and Kappe cells, with hyper-activity of mucous secretion from goblet cells. At the genetic level, ZnO-NPs could activate the reactive oxygen species (ROS) synthesis expected by the down-regulation of mRNA expression for the antioxidant-related genes and up-regulation of DNA damage, cell growth arrest, and apoptosis. Interestingly, ZnO-NPs affected the odor sensation at 60 days post-treatment (60-dpt) more than at 30-dpt, severely damaging the olfactory epithelium and irreparably affecting the cellular repairing mechanisms. This induced a dramatically adverse effect on the cellular endoplasmic reticulum (ER), revealed by higher CHOP protein expression, that suppresses the antioxidant effect of Nrf2 and is followed by the induction of apoptosis via the up-regulation of Bax expression and down-regulation of Bcl-2 protein.

Dunaliella salina Microalga Restores the Metabolic Equilibrium and Ameliorates the Hepatic Inflammatory Response Induced by Zinc Oxide Nanoparticles (ZnO-NPs) in Male Zebrafish.

Microalgae are rich in bioactive compounds including pigments, proteins, lipids, polyunsaturated fatty acids, carbohydrates, and vitamins. Due to their non-toxic and nutritious characteristics, these are suggested as important food for many aquatic animals. Dunaliella salina is a well-known microalga that accumulates valuable amounts of carotenoids. We investigated whether it could restore the metabolic equilibrium and mitigate the hepatic inflammation induced by zinc oxide nanoparticles (ZnO-NPs) using male zebrafish which were exposed to 1/5th 96 h-LC50 for 4 weeks, followed by dietary supplementation with D. salina at two concentrations (15% and 30%) for 2 weeks. Collectively, ZnO-NPs affected fish appetite, whole body composition, hepatic glycogen and lipid contents, intestinal bacterial and Aeromonas counts, as well as hepatic tumor necrosis factor- α (TNF-α). In addition, the mRNA expression of genes related to gluconeogenesis (pck1, gys2, and g6pc3), lipogenesis (srepf1, acaca, fasn, and cd36), and inflammatory response (tnf-α, tnf-ß, nf-kb2) were modulated. D. salina reduced the body burden of zinc residues, restored the fish appetite and normal liver architecture, and mitigated the toxic impacts of ZnO-NPs on whole-body composition, intestinal bacteria, energy metabolism, and hepatic inflammatory markers. Our results revealed that the administration of D. salina might be effective in neutralizing the hepatotoxic effects of ZnO-NPs in the zebrafish model.

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.