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Fig. 6 The role of the histamine pathway in porphyrin-stressed PMHs. Primary mouse hepatocytes (PMHs) were challenged with ALA + DFO that results in porphyrin accumulation, then treated with histamine (HT), CCZ, or other histamine blockers for 12 hours. (A) PMHs were treated with HT, the H1-blocker fexofenadine (FXF), and the H2-blockers cimetidine (CMT) and ranitidine (RNT) at the indicated doses. Intracellular and culture medium PP-IX levels following the treatments are shown. (B) CCZ and CMT were tested individually at 10 μM. Intracellular and medium PP-IX levels were measured in the absence of histamine. (C) CCZ and CMT were tested individually at 10 μM by treating primary mouse hepatocyte cultures. Intracellular and culture medium PP-IX levels in the presence or absence of histamine with levels relative to the condition without histamine. Data are shown as mean ± SD (n ≥3 experiments). Statistical analysis was performed by 1-way ANOVA test, ∗∗∗P < .001; ∗∗P < .01; ∗P < .05.