http://repositorio-aberto.up.pt/bitstream/10216/9155/2/Ghrelin%20desacyl%20ghrelin%20and%20obestatin%20Three%20pieces%20of%20the%20same%20puzzle.pdf

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle.

The gastroduodenal mucosa withstands injury from acid, drugs, foodstuffs, and other factors. Defense mechanisms include pre-epithelial and epithelial barriers, submucosal acid sensors, prostaglandin generation, endogenous protective gases, and other chemical mediators. Recent studies have focused on proteinase-activated receptors and their linkage to prostaglandin formation, as well as on antioxidants targeted to reduce harmful reactive oxygen species. Investigation continues into the protective roles of calcitonin gene-related peptide, hydrogen sulfide, annexin-1, survivin, and methylnicotinamide. This article also summarizes some new findings on the genetics of ulcer formation and the effects of age and gender on mucosal defense and touches on current developments in drugs, including considerations for future therapeutic agents.

Gastroduodenal Mucosal Defense

https://www.aido.it/uploads/2/515_Moreno_et_al_Hepatology_Vol_51_No_3_2010.pdf

Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans

Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-κB pathways and mitochondrial protective mechanisms

Nitric oxide (NO) and hydrogen sulfide (H2S) are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes NO is produced from l-arginine by constitutive NO synthase (NOS) and inducible NOS enzymatic pathways This gaseous mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the vessel homeostasis NO is known as a vasodilatory molecule involved in control of the gastric blood flow (GBF) and the maintenance of gastric mucosal barrier integrity in either healthy gastric mucosa or that damaged by strong irritants Biosynthesis of H2S in mammals depends upon two enzymes cystathionine-β-synthase and cystathionine γ-lyase This gaseous mediator, similarly to NO and carbon monoxide, is involved in neuromodulation, vascular contractility and anti-inflammatory activities For decades, H2S has been known to inhibit cytochrome c oxidase and reduce cell energy production Nowadays it is generally considered to act through vascular smooth muscle ATP-dependent K+ channels, interacting with intracellular transcription factors and promote sulfhydration of protein cysteine moieties within the cell, but the mechanism of potential gastroprotective and ulcer healing properties of H2S has not been fully explained The aim of this review is to compare current results of the studies concerning the role of H2S and NO in gastric mucosa protection and outline areas that may pose new opportunities for further development of novel therapeutic targets

/pdf/gaseous-mediators-nitric-oxide-and-hydrogen-sulfide-in-the-404s5lr2yy.pdf

Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing.

Background and Aim: Gherlin, an endogenous ligand for the growth hormone secreta- gogue receptor (GHS-R), is produced by stomach cells. It regulates food intake, gastric secretion and motility. However, its role as a protective agent in gastric ischemia/ reperfusion (I/R) injury has not yet been investigated. Therefore, the objectives of the present study were to: (i) test the in vivo effect of peripherally administered ghrelin on gastric I/R-induced lesions in rats; and (ii) investigate in vitro the effect of ghrelin on reactive oxygen species (ROS) production by human polymorphoneuclear (PMN) cells. Methods: The present study was carried out on three groups of rats (six per group): control (sham-operated), I/R (clamping of celiac artery for 30 min and reperfusion for 1 h), and I/R + ghrelin (200 ng/kg i.v., 15 min before ischemia and before reperfusion, respectively). Histological assessment of hematoxylin and eosin stained sections was performed and immunostaining with inducible nitric oxide (iNOS) antibody were performed on a gastric paraffin embedded section. Oxidative stress markers thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) were measured in gastric tissue homogenates. Serum lactic acid dehydrogenase (LDH) was determined. Tumor necrosis factor-alpha (TNF-a) was assayed in gastric tissue homogenate. Gastric permeability was assessed calorimetri- cally using Evans blue dye. In vitro studies were carried out on isolated human PMN cells incubated with ghrelin and tested for ROS generation as measured by chemiluminecence (CL). Results: Peripheral administration of ghrelin attenuated gastric injury by reducing ulcer- ation, tissue congestion, cellular infiltration and vascular permeability. Serum level of LDH and tissue content of TNF-a were markedly reduced. A decrement in TBARS and an increment in GSH were observed. Ghrelin treatment attenuated iNOS protein expression which was upregulated by gastric ischemic injury. In vitro studies showed for the first time that ghrelin inhibited ROS generation by human PMN in a dose-dependent manner. Conclusions: These results provide evidence that peripherally administered ghrelin pro- tects against gastric I/R injury. We also demonstrated that this protection is possibly accomplished through the antioxidant activity of ghrelin observed in vivo and in vitro.

Ali Al Tuwaijiri

Papers

In vivo and in vitro antioxidant activity of ghrelin: Attenuation of gastric ischemic injury in the rat