Heme overload inhibits the growth of normal rats

We have developed a model with which to evaluate the direct metabolic effect of circulating heme in chronic hemolytic diseases. Normal rats were injected with heme intraperitoneally (IP) using different treatment schedules and then killed so their growth parameters could be measured; heme injections were well tolerated, but final body weight was decreased in the heme treated groups. In one experiment, we used heme 40 mg/kg IP 2x/d for 8 d and found that overall growth was significantly inhibited (weight increment in the heme-treated group +45 +/- 3g vs +65 +/- 3g in the controls, P less than .05); although serum somatomedin activity was significantly diminished, the liver extract somatomedin activity was not decreased. In another experiment, we compared the effect of heme 40 mg/kg versus heme 80 mg/kg IP 2x/d for 5 d: growth inhibition was dose-dependent (weight change +31 +/- 2g for vehicle-treated group versus +12 +/- 3 grams for heme 40 mg/kg group versus -6 +/- 5 grams for heme 80 mg/kg group) and related to serum heme levels (3.53 +/- 0.47 mcM for vehicle group versus 5.42 +/- 0.71 mcM for heme 40 mg/kg versus 10.91 +/- 0.84 mcM for heme 80 mg/kg group). Our data demonstrate that IP heme administration is feasible and provides a valid approach with which to identify the potential direct metabolic consequences of abnormally circulating heme and its contribution to the growth retardation associated with chronic hemolytic diseases.