Histamine protects against the acute phase of experimentally-induced hepatic ischemia/re-perfusion

Histamine H4 receptors in the gastrointestinal tract

“…Recently, the mechanism of action was further elucidated by El‐Mahdy et al . (). They found that liver damage was significantly reduced by pretreatment with histamine, remained unaffected by a selective H 1 or H 2 receptor antagonist, was abolished by the H 3 /H 4 receptor antagonist thioperamide and was reproduced by the H 3 /H 4 receptor agonist clozapine.…”

“…This protective effect was abolished by the H3/H4 receptor antagonist thioperamide but remained unaffected by the selective H2 receptor antagonist cimetidine, suggesting a beneficial influence of H4 receptor stimulation in the prevention of ischaemia/reperfusion liver damage. Recently, the mechanism of action was further elucidated by El-Mahdy et al (2013). They found that liver damage was significantly reduced by pretreatment with histamine, remained unaffected by a selective H1 or H2 receptor antagonist, was abolished by the H3/H4 receptor antagonist thioperamide and was reproduced by the H3/H4 receptor agonist clozapine.…”

“…They found that liver damage was significantly reduced by pretreatment with histamine, remained unaffected by a selective H1 or H2 receptor antagonist, was abolished by the H3/H4 receptor antagonist thioperamide and was reproduced by the H3/H4 receptor agonist clozapine. The protective effect of histamine and clozapine was mediated by attenuating TNF-α and IL-12 secretion and consequently reduced reactive oxygen species (El-Mahdy et al, 2013). As H3 receptors were absent from adult mouse liver tissue (Heron et al, 2001), it seems reasonable to assume that the protective effect of histamine and clozapine was indeed mediated by H4 receptors.…”

Histamine restores biliary mass following carbon tetrachloride-induced damage in a cholestatic rat model

“…During hepatic ischaemia/reperfusion, histamine (via H4HR) reduces the damaging effects ischaemia/reperfusion including lowering plasma ALT and AST levels and glutathione content. It was found that only the H4HR agonist mimicked the effects induced by histamine suggesting that this receptor is important in protecting the liver against ischaemic damage [32]. In LPS-induced liver injury that increases the number of necrotic and apoptotic hepatocytes, treatment with histamine mitigated the increase in apoptosis and decreased caspase-3 activity compared to control-treated mice [33].…”

Suppression of peritoneal thickening by histamine in a mouse model of peritoneal scraping

“…Histamine H 2 action reduced inflammatory cell recruitment during reperfusion phase and ameliorated brain damage caused by transient ischemia [14,15]. In the liver, histamine H 4 action reduced production of proinflammatory cytokines and suppressed ischemia-induced liver damage [16][17][18]. Considering that no treatment is currently available for progressive thickening of the peritoneum in patients undergoing peritoneal dialysis, histaminergic ligands may give rise to new ideas for therapeutic intervention.…”