Dietary zinc can generate Zn‐protoporphyrin, reduce endogenous formation of CO and stem bleeding in soft tissue injury

Zinc‐protoporphyrin (ZnPP) can reduce formation of heme oxygenase (HO) derived carbon monoxide (CO) to stem bleeding which arises in hepatic trauma. But, the cost and experience required for iv administration of ZnPP limits its prophylactic use in high trauma risk occupations. Since urinary ZnPP has been used as a clinical marker for Zn poisoning, the current study was conducted to determine if dietary Zn may be used to promote the formation ZnPP and reduce the formation of HO derived CO. For this purpose, male SD rats were provided diets with 0.01, 0.1 or 0.5% Zn (n=6 each) for five days. At the end of the dietary period increased levels of Zn intake were associated with increased levels of ZnPP in the urine (0.6±0.2, 2.9±2.0, 6.1±2.8 μM) and the plasma (0.1±0.1, 1.9±1.6, 2.5±1.0 μM), that were paralleled by decreased rates of whole animal CO excretion (915±18, 750±46 and 692±39 nmol/Kg per hr). Animals on the elevated Zn diets displayed only modest elevations in the MAP (109±1, 117±5 and 118±5 mmHg, low to high). Hct and Hb were unaffected by the diets. Finally, animals provided 0.1% Zn diets displayed stemmed bleeding from our previously established “corkscrew” injury. The findings show that prudent supplementation of dietary Zn can be used to promote endogenous generation of ZnPP, inhibit CO formation and may be used as a practical alternative to iv administration of metalloporphyrins as a prophylactic to stem soft tissue bleeding. NIH/NHLBI RO1 grant HL64577