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Indian Journal of Dermatology, Venereology and Leprology
Medknow Publications on behalf of The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL)
ISSN: 0378-6323 EISSN: 0973-3922
Vol. 74, Num. 2, 2008, pp. 158-159

Indian Journal of Dermatology, Venereology and Leprology, Vol. 74, No. 2, March-April, 2008, pp. 158-159

Letter To Editor

Hypothesis: The potential utility of topical eflornithine against cutaneous leishmaniasis

Namazi MR

Department of Dermatology, Shiraz University of Medical sciences, Shiraz
Correspondence Address:Department of Dermatology, Faghihi Hospital, Zand Street, Shiraz, namazi_mr@yahoo.com

Code Number: dv08060

Sir,

The trypanothione biosynthetic pathway is common to the trypanosomatid family of protozoa, which includes Leishmania and Trypanosoma, and is absent in the host systems. This pathway constitutes an important target for chemotherapy against leishmaniasis. The trypanothione pathway combines two metabolic pathways: the glutathione and the polyamine biosynthetic pathways, to produce trypanothione, a glutathione-spermidine conjugate. [1]

The levels of trypanothione are increased in the Leishmania parasite selected for resistance to the heavy metal, arsenic. The levels of putrescine and spermidine were increased in resistant mutants. This increase is mediated by overexpression of ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. [2] Fluorinated analogues of L-ornithine are powerful inhibitors of ornithine decarboxylase and inhibit the cell growth of L. infantum promastigotes. [3]

Eflornithine was originally used orally in the treatment of childhood hyperactivity. [4] It was used as an anti-cancer drug in 1970 [5] and was later used intravenously in the treatment of African sleeping sickness. [5],[6] Interestingly, hair loss was observed as an adverse effect of this treatment. [5],[7] Eflornithine hydrochloride cream (13.9%) is the first topical preparation approved by the FDA in August 2000 for the reduction of facial hirsutism in women. [5] It is a potent inhibitor of ornithine decarboxylase. A topical formulation of this agent has been used for treatment of hirsute women as inhibition of ornithine decarboxylase delays the initiation of anagen and keeps hair in telogen. Therefore, eflornithine does not remove the excess hair but it causes slowing of excessive hair growth.

Given the important role of ornithine decarboxylase in the trypanothione biosynthetic pathway, eflornithine could prove to be effective against leishmaniasis. Combining this agent with glucantime could potentiate the therapeutic response of the latter and break the resistance of the resistant strains against it. Clinical studies on this subject are warranted.

References

1.Kapoor P, Sachdev M, Madhubala R. Inhibition of glutathione synthesis as a chemotherapeutic strategy for leishmaniasis. Trop Med Int Health 2000;5:438-42.  Back to cited text no. 1    
2.Haimeur A, Guimond C, Pilote S, Mukhopadhyay R, Rosen BP, Poulin R, et al. Elevated levels of polyamines and trypanothione resulting from overexpression of the ornithine decarboxylase gene in arsenite-resistant Leishmania. Mol Microbiol 1999;34:726-35.  Back to cited text no. 2    
3.Reguera RM, Fouce RB, Cubria JC, Bujidos ML, Ordonez D. Fluorinated analogues of L-ornithine are powerful inhibitors of ornithine decarboxylase and cell growth of Leishmania infantum promastigotes. Life Sci 1995;56:223-30.  Back to cited text no. 3    
4.De Berker DA, Messenger AG, Sinclair RD. Disorders of hair. In : Rook's Textbook of Dermatology, Burns T, Breathnach S, Cox N, Griffiths C, editors. 7 th ed, Vol.4, London: Blackwell Science; Chapter 63, 2004. p. 63.106  Back to cited text no. 4    
5.Jobanputra KS, Rajpal AV, Nagpur NG. Eflornithine. Indian J Dermatol Venereol Leprol 2007;73:365-6.  Back to cited text no. 5    
6.Powell P, Lucas K. Vaniqa (eflornithine hydrochloride). New Drug Update 2002;8:3.  Back to cited text no. 6    
7.Coyne P. The eflornithine story. J Am Acad Dermatol 2001;45:784-6.  Back to cited text no. 7    

Copyright 2008 - Indian Journal of Dermatology, Venereology and Leprology

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