Histamine at low concentrations aggravates rat liver BRL-3A cell injury induced by hypoxia/reoxygenation through histamine H2 receptor in vitro

Aim Histamine released from mast cell degranulation participates in the pathogenesis of ischemia/reperfusion injury. The purpose of our study was to define the role of histamine in hypoxia/reoxygenation mediated liver cell injury and to elucidate the underlying mechanism in vitro. Methods Histamine alone or in combination with H1 receptor antagonist (pyrilamine), H2 receptor antagonist (cimetidine) or H3/4 receptor antagonist (thioperamide) at different concentrations before hypoxia was added to rat liver BRL-3A cell which was subjected to 24 h hypoxia followed by 4 h reoxygenation. Cell proliferation, apoptosis and the changes of ultrastructure were assessed, and MDA contents, SOD activities and ALT levels were quantified as well. Results Histamine (from 10−3 to 10−9 M) did not affect the growth of BRL-3A cells without hypoxia treatment. However, histamine 10−8 M significantly lowered the growth of BRL-3A cells challenged by hypoxia/reoxygenation, accompanied with concomitant elevations in MDA contents and decreases in SOD activities, all these changes were blocked by cimetidine, not by pyrilamine or thioperamide. However, histamine (above 10−6 M) did not show exacerbating effects in BRL-3A cell subjected to hypoxia/reoxygenation. Conclusion Histamine at low concentrations (10−7–10−9 M) aggravates hypoxia/reoxygenation mediated BRL-3A damage through histamine H2 receptor.