Zinc protoporphyrin

Clinical utility

Measurement of zinc protoporphyrin in red cells has been used for screening for lead poisoning and for iron deficiency.

Zinc protoporphyrin levels can be elevated as the result of a number of conditions, for instance:

• lead poisoning
• iron deficiency
• sickle cell anemia
• sideroblastic anemia
• anemia of chronic disease
• vanadium exposure
• erythropoietic protoporphyria

The fluorescent properties of ZPP in intact red cells allows the ZPP/heme molar ratio to be measured quickly, at low cost, and in a small sample volume.

History

Porphyrin complexes of zinc have been known since the 1930s. In 1974 ZPP was identified as a major non-heme porphyrin formed in red cells as the result of lead poisoning or iron deficiency., It was already known at this time that non-heme protoporphyrin IX levels were elevated in these conditions, but prior investigators had used acidic extraction methods in their assays that converted ZPP to unbound Protoporphyrin IX. The early literature on quantifying zinc-PP levels may be unreliable.

Early-stage cancer research

ZnPP is under in vitro research for its potential effects on cancer cells. ZnPP is a competitive inhibitor of heme oxygenase, which is a cytoprotective enzyme with higher expression in cancerous tissues. In vitro, ZnPP suppression of heme oxygenase reduces cell viability of cancer cells and increases cytotoxicity in cancer cells.

In preliminary human studies conducted in 2014, ZnPP in combination with anticancer drugs increased cytotoxicity of cancer cells. Tumors from several types of cancer showed a susceptibility to ZnPP due to increased expression of heme oxygenase.

ZnPP has been encapsulated in nanoparticles with a specialized coating for drug delivery inside the body. ZnPP did not show any reduced inhibitory potential on heme oxygenase when loaded into nanoparticles.

References

References

1. (December 1999). "Zinc protoporphyrin: A metabolite with a mission". Clinical Chemistry.
2. (December 2004). "The interpretation of zinc protoporphyrin changes in lead intoxication: a case report and review of the literature". Occupational Medicine.
3. (1987). "Zinc protoporphyrin as an indicator of lead exposure: precision of zinc protoporphyrin measurements". International Archives of Occupational and Environmental Health.
4. (July 2006). "Comparative effectiveness of zinc protoporphyrin and hemoglobin concentrations in identifying iron deficiency in a group of low-income, preschool-aged children: practical implications of recent illness". Pediatrics.
5. (September 2010). "Liver disease and erythropoietic protoporphyria: a concise review". World Journal of Gastroenterology.
6. (February 1977). "The hematofluorometer". Clinical Chemistry.
7. (December 1974). "Zinc protoporphyrin in the erythrocytes of patients with lead intoxication and iron deficiency anemia". Science.
8. (June 1973). "A micromethod for free erythrocyte porphyrins: the FEP test". The Journal of Laboratory and Clinical Medicine.
9. (2012-04-13). "Crucial role of heme oxygenase-1 on the sensitivity of cholangiocarcinoma cells to chemotherapeutic agents". PLOS ONE.
10. (August 2014). "Zinc protoporphyrin polymeric nanoparticles: potent heme oxygenase inhibitor for cancer therapy". Pharmaceutical Research.
11. (August 2012). "Involvement of heme oxygenase-1 in Korean colon cancer". Tumour Biology.
12. (June 2014). "Upregulation of heme oxygenase-1 in colorectal cancer patients with increased circulation carbon monoxide levels, potentially affects chemotherapeutic sensitivity". BMC Cancer.