|MadSci Network: Cell Biology|
A search of the PubMed and of Google web sites did not yield a scientific study that directly answers your question. I was not able to find any evidence that phenamil does cause red blood cell lysis, or hemolytic anemia. In addition, I was unable to find any evidence that the related compound, amiloride, causes red blood cell lysis. Therefore, unfortunately, I can't offer you any insight into explaining your results, other than to inquire whether you have controlled for the solvent that you have used to dissolve the phenamil, as it is insoluble in water. Now, for the sake of scientific inquiry, letís hypothesize that phenamil causes hemolysis as the result of altered levels of copper in the blood. Although I was unable to find any evidence that phenamil alters blood copper levels, here is the basis for the hypothesis. Phenamil inhibits sodium ion absorption, and thus is useful in the treatment of cystic fibrosis (Kunzelmann and Mall 2001). Copper uptake in some cells occurs, at least in part, via sodium channels and is blocked by phenamil (Grosell and Wood 2002). If phenamil were able to sufficiently increase blood copper levels, secondary to its effects on sodium and copper ion absorption, then this could cause hemolysis, as high blood levels of copper (e.g., occur in Wilsonís disease) can cause lysis of red blood cells (Lovstad 1982, Saenko et al. 1990). See also, the Merck Manual web site (http://www.merck.com/pubs/mmanual/section1/chapter4/4j.htm) It seems very unlikely to me that this mechanism could explain your data. Most importantly, I encourage you to keep thinking about this problem. You may have discovered an intersting property of the drug, which may be useful in the study of red blood cell ion transport mechanisms. Good luck. REFERENCES Kunzelmann, K. and Mall, M. (2001) Pharmacotherapy of the ion transport defect in cystic fibrosis. Clinical and Experimental Pharmacology and Physiology 28, 857-867. Lovstad, R.A. (1982) The protective action of ceruloplasmin on copper ion stimulated lysis of rat erythrocytes. International Journal of Biochemistry 14, 585-589.. Saenko, S.L., Skorobatíko, O.V. and Yaropolov, A.L. (1990) Interrelation between structure and protective action of normal and pathological ceruloplasmins during copper-induced lysis of red blood cells. Biochemistry international 22, 749-757. Grosell, M. and Wood, C.M. (2002) Copper uptake across rainbow trout gills: mechanism of apical entry. The Journal of Experimental Biology 205, 1179-1188.
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