Splanchnic-aortic inflammatory axis in experimental portal hypertension

Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension.This experimental model causes minimal alternations in the liver,thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension.Low-grade splanchnic inflammation after longterm triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy.In fact,we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans.Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension.Among the systemic impairments,aortopathy characterized by oxidative stress,increased levels of proinflammatory cytokines and profibrogenic mediators stand out.In this experimental model of long-term triple portal vein ligated-rats,the abdominal aortic proinflammatory response could be attributed to oxidative stress.Thus,the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate[NAD(P)H]oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation.Also,oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis.The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension.

Allicin neuroprotective effect during oxidative/inflammatory injury involves AT1-Hsp70-iNOS counterbalance axis

The ancestral cultures have described many therapeutic properties of garlic,therefore,it is of central interest to elucidate the molecular basis explaining this millenary empirical knowledge.Indeed,it has been demonstrated a neuroprotective effect of allicin–a phytochemical present in garlic-linked to oxidative-inflammatory modulation.Allicin improved neuronal injury by heat shock protein 70(Hsp70)and inducible nitric oxide synthase(iNOS)regulation.Also,allicin exerts renal protection involving a possible angiotensin type 1 receptor(AT1)interaction.In connection,AT1 overexpression has been recognized as a central deleterious factor in many brain diseases.However,there are no studies that evaluate AT1-Hsp70-iNOS interaction as a mechanism linked to neuroinflammation.Thus,our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-iNOS counterbalance axis.For this study,a murine microglial cell line(BV-2)was injured with lipopolysaccharides and treated or not with allicin.Then,it was evaluated cell viability,proinflammatory cytokine levels,cellular oxidative stress,iNOS,Hsp70,and AT1 protein expression(cellular and mitochondrial fractions),nitrite levels,and protein-protein interactions.The results demonstrated that allicin could prevent neuronal injury due to a reduction in oxidative stress and inflammatory status mediated by an AT1-Hsp70-iNOS counterbalance axis linked to direct protein-protein interaction.