Agata Torre

Effects of palmitoylethanolamide on intestinal injury and inflammation caused by ischemia‐reperfusion in mice

Our primary aim in this study was to test the hypothesis that PEA, a member of the fatty acid ethanolamide family and an endogenous PPAR‐α ligand, exerts anti‐inflammatory effects on SAO shock, causing a severe form of circulatory shock and enhanced formation of ROS. SAO shock was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. In this study, we demonstrated that the administration of PEA, 5 min before reperfusion, significantly reduced all of the parameters involved during inflammation, such as proinflammatory cytokine production (TNF‐α, IL‐1β), adhesion molecules (ICAM‐1, P‐selectin) expression, NF‐κB expression, and apoptosis (Bax, Bcl‐2, TUNEL assay) activation. In addition, to study whether the protective action of PEA on SAO shock is also related to the activation of PPAR‐α, we have investigated the effect of PEA in PPAR‐α KO mice subjected to SAO shock. Our study clearly demonstrates that PEA significantly attenuated the degree of intestinal injury and inflammation caused by I/R injury. Moreover, the positive effects of PEA were at least in part dependent on the PPAR‐α pathway. The results clearly indicate that PEA exerts an anti‐inflammatory effect, also in a SAO shock model, which could imply a future use of PEA in the treatment of I/R shock.

Effect of CdCl2 on Regulatory Volume Decrease (RVD) in Mytilus galloprovincialis digestive cells.

This study investigated the role of cadmium, a widespread heavy metal in the aquatic environment, on cell volume regulation of digestive cells isolated from the digestive gland of Mytilus galloprovincialis. These cells when exposed to a rapid change (from 1100 to 800 mOsm/kg) of the bathing solution osmolality swelled but thereafter underwent a Regulatory Volume Decrease (RVD), tending to recover the original size. This homeostatic response is altered by cadmium, as suggested by experiments performed both on isolated cells pre-incubated with cadmium (10(-5)M) and on cells isolated from animals exposed to sub-lethal concentrations of the metal (40 μg/l for 21 days). It is suggested that cytoskeleton and Na(+)/K(+)ATPase are the possible targets of cadmium which impairment is responsible of the altered homeostatic response.

Digestive cells from Mytilus galloprovincialis show a partial regulatory volume decrease following acute hypotonic stress through mechanisms involving inorganic ions.

The response of isolated digestive cells of the digestive gland of Mytilus galloprovincialis to hypotonic shock was studied using videometric methods. The isolated cells exposed to a rapid change (from 1100 to 800 mosmol kg−1) of the bathing solution osmolality swelled but thereafter underwent a regulatory volume decrease (RVD), tending to recover the original size. When the hypotonic stress was applied in the presence of quinine and glibenclamide, known inhibitors of swelling activated ion channels, the cells did not exhibit an RVD response; in addition, they showed a larger increase in size in respect to control cells. These observations suggest that the digestive cells of the digestive gland have the machinery to cope with the hyposmotic shock allowing them to exhibit a small but significant RVD preventing an excessive increase in cell size. The pharmacological treatment of digestive cells during the RVD experiments suggests that cell volume is regulated by K+ and Cl− efflux followed by an obliged water efflux from the cell. The involvement of organic osmolytes such as taurine and betaine seems to be excluded by NMR measurement on digestive cells. Copyright

Cell volume regulation following hypotonic shock in hepatocytes isolated from Sparus aurata

The response of isolated hepatocytes of Sparus aurata to hypotonic shock was studied by the aid of videometric and light scattering methods. The isolated cells exposed to a rapid change (from 370 to 260 mOsm/kg) of the osmolarity of the bathing solution swelled but thereafter underwent a decrease of cell volume tending to recovery the original size. This homeostatic response RVD (regulatory volume decrease) was inhibited in the absence of extracellular Ca²+ and in the presence of TMB8, an inhibitor of Ca²+ release from intracellular stores. It is likely that Ca²+ entry through verapamil sensitive Ca²+-channels, probably leading to a release of Ca²+ from intracellular stores, is responsible for RVD since the blocker impaired the ability of the cell to recover its volume after the hypotonic shock. RVD tests performed in the presence of various inhibitors of different transport mechanisms, such as BaCl₂, quinine, glybenclamide and bumetanide as well as in the presence of a KCl activator, NEM, led us to suggest that the recovery of cell volume in hypotonic solution is accomplished by an efflux of K+ and Cl⁻ through conductive pathways paralleled by the operation of the KCl cotransport, followed by an obliged water efflux from the cells.

Sulfenic acid – derived glycoconjugated disulfides and sulfoxides: a biological evaluation on human red blood cells

This article examines the effects of some glycoconjugated disulfides and sulfoxides on red blood cells (RBCs). Compounds under study show sugar units connected directly or through a benzene platform, and have been obtained following synthetic pathways based on the sulfenic acid chemistry. In order to evaluate the relationship between the structural features of the thioglycoconjugates under investigation and their potential biological activity, we were interested in assessing both the cytotoxicity and hemolytic activity produced on human RBCs by overnight exposition to the thioglycoconjugates. The absence of both cytotoxic effect and hemolysis produced by the tested compounds on erythrocytes supports the rational design of hemocompatible molecules for biomedical applications. GRAPHICAL ABSTRACT

Purinergic receptors and regulatory volume decrease in seabream (Sparus aurata) hepatocytes: a videometric study

The response of isolated hepatocytes of Sparus aurata to hypotonic stress was studied by the aid of videometric methods with the aim to investigate the possible involvement of ATP in the regulatory volume decrease (RVD). This study confirms our previous observations showing the ability of these cells to undergo RVD. In addition, it shows that the homeostatic response was inhibited by apyrase, an ATP scavenger, thus suggesting the involvement of extracellular ATP in the RVD response. Experiments performed in the presence of ATPγS or adenosine, agonists of P2 and P1 receptors respectively, and in the presence of suramin or 8-PT, antagonists of P2 and P1 receptors respectively, suggest that ATP exerts its stimulatory effect on the homeostatic response by interacting with P2 receptors. On the other hand, the activation of P1 receptors by ATP metabolites produces opposite effects. In an attempt to clarify the mechanisms involved in ATP release from the cell, we performed some experiments with known inhibitors of the possible mechanisms of regulated ATP release. The results we obtained let us to suppose that the mechanism allowing the exit of ATP from the cell is verapamil sensitive suggesting the involvement of the P-glycoprotein.