Antecedent Ethanol Ingestion Prevents Postischemic P‐Selectin Expression in Murine Small Intestine

Abstract

The data indicate that antecedent ethanol exposure prevents postischemic P-selectin expression on day 2 by a mechanism that is triggered by adenosine A2 receptor activation and the formation of nitric oxide (NO) and reactive oxygen species (ROS) during the period of ethanol exposure on day 1.

5′-AMP-activated protein kinase activation prevents postischemic leukocyte-endothelial cell adhesive interactions

“…Indeed, it is well established that in addition to activating AMPK, AICAR administration also increases tissue levels of the potent antiadhesive purine nucleoside adenosine, which has been implicated as a trigger for the development of other forms of PC (15). However, this hypothesis seems unlikely in view of the fact that late-phase PC with adenosine or adenosine receptor agonists prevents both leukocyte rolling and stationary leukocyte adhesion (14,47). Clearly, much additional work will be required to elucidate the mechanisms underlying the differential role of AICAR-induced eNOS activation to prevent leukocyte rolling without influencing postischemic leukocyte adhesion.…”

“…As a result of this work, several pharmacological agents are now known to induce a protective phenotype similar to that seen with IPC, such as PC with ethanol, adenosine receptor agonists, bradykinin, nitric oxide (NO) donors, and exogenous calcitonin gene-related peptide (4,9,26,41,43). Indeed, our own work (13,14,23,24,36,37,47) has established that these agents induced the development of a protective anti-inflammatory phenotype in postcapillary venules, such that these vessels fail to support adhesion molecule expression, leukocyte rolling and adhesion, and increased vascular permeability when the small bowel is subsequently exposed to prolonged ischemia-reperfusion (I/R).…”

Ethanol preconditioning protects against ischemia/reperfusion-induced brain damage: Role of NADPH oxidase-derived ROS

“…More recent work has demonstrated that these protective effects are triggered by oxidants generated during ischemic preconditioning (66). In addition, we have previously demonstrated that ethanol preconditioning induces the development of an anti-inflammatory phenotype in postcapillary venules by a mechanism involved oxidants generated during the first hour after ethanol ingestion [13,19]. Taken together, our studies indicate that NADPH-oxidase derived oxidants can play dual and opposing roles in I/R, serving to produce neuronal injury in brains exposed to I/R alone and by acting as important initiators in the signaling cascade that is activated by antecedent ethanol ingestion to produce a neuroprotective phenotype.…”

“…However, it is becoming increasingly apparent that these reactive molecules can also participate in a number of normal physiologic phenomena (16,17). Indeed, we have demonstrated a role for ethanol-induced NADPH oxidase-derived oxidants in the appearance of anti-adhesive and anti-inflammatory phenotype in postcapillary venules that becomes apparent on subsequent exposure to I/R (13,18,19). However, whether ethanol also exerts neuroprotective effects in stroke is unknown.…”

Ethanol Preconditioning Reduces Hepatic I/R Injury by Inhibiting the Complement System Activation

“…Ethanol preconditioning (EtOH-PC) refers to a phenomenon in which tissues are protected from the deleterious effects of ischemia/reperfusion (I/R) by prior ingestion of ethanol at low to moderate levels. There is evidence that moderate consumption of ethanol alone also exerts protective effects against injury due to cerebral, intestine, and myocardial ischemia [10][11][12][13][14]. It is suggested that low-dose ethanol attenuates the gut I/Rinduced hepatic microvascular dysfunction and sequential liver injury [15].…”