Figure 1

Histamine decreases doxorubicin-induced cardiotoxicity and hepatotoxicity in rats and mice. (A) (a, d) Normal histological appearance of untreated heart. (b, e) Heart of Dox-treated animals displaying focal necrotic cell death (black arrow), congestion-hemorrhage (red arrow), myocytolysis (yellow arrow) and myofribrillolysis (blue arrow) with fibrils de-arrangement. (c, f) Heart of Dox+HA-treated animals showing evident preservation of heart structure with reduced myofibrillolysis (blue arrow) and muscle bands with normal appearance. (a–c) Representative H&E stained specimens and (d–f) immunohistochemical images of γH2AX sections are shown. (B) (a, d, g, j) Normal histological appearance of liver from untreated animals. (b, e, h, k) Liver of Dox-treated rats displaying de-arrangement of hepatic trabecula (red arrow), cellular edema and focal necrosis (black arrow). (c, f, i, l) Liver of Dox+HA-treated animals showing preservation of tissue structure with mild cellular edema. (a–c) Representative H&E-stained sections are shown. (d–f) Representative immunohistochemical images of TUNEL, (g–i) caspase 3 and (j–l) γH2AX in paraffin-embedded liver specimens. Arrows indicate TUNEL-positive cells. (Six to eight rats per group). (C) (a) Normal histological appearance of WT mice untreated heart. (b) Heart of Dox-treated animals displaying vascular damage with perivascular edema, myofribrillolysis (blue arrow), cell recruitment (yellow arrows) and focal necrosis (black arrows). (c) Heart of Dox+HA-treated animals showing minimal focal damage with muscle bands with normal appearance. (d) Normal histological appearance of untreated heart of H4R^−/− mice. (e) Heart of Dox-treated H4R^−/− mice displaying myofibrillolysis (blue arrow), cell mobilization (yellow arrows) and focal necrosis (black arrow). (f) Heart of Dox+HA-treated H4R^−/− mice showing minimal focal damage (non-diffused), including rippled and non-extended myofibrillolysis, with vasculature with normal appearance. (D) (a) Normal histological appearance of untreated liver of WT mice. (b) Liver of Dox-treated animals displaying two different areas, an extended necrotic region and a normal area, between them cellular mobilization as a band (arrow) (c) Liver of Dox+HA-treated WT mice showing almost normal characteristics. (d) Normal histological appearance of liver of untreated H4R^−/− mice. (e) Liver of Dox-treated H4R^−/− displaying reduced histological damage with focal and non-diffuse necrotic areas without cell mobilization. (f) Liver of Dox+HA-treated H4R^−/− showing preservation of hepatic structure. Representative H&E stained sections are shown. x630 Original magnification. Scale bar, 20 μm. Inset: image at x100-fold magnification. (8–12 Mice per group).