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Horm Metab Res 2004; 36(3): 155-163
DOI: 10.1055/s-2004-814339
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Systematic Investigation of Different Steroid Precursors with Respect to their Effect on Superoxide Anion Production by Human Neutrophil Granulocytes

G.  Békési1 , K.  Rácz1 , A.  Hrabák6 , R.  Kakucs1 , S.  Várbíró3 , Z.  Magyar2 , J.  Fehér1 , E.  Dinya4 , T.  Pázmány5 , S.  Paku7 , B.  Székács1
  • 12nd Department of Medicine, Semmelweis University, Budapest, Hungary
  • 21st Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
  • 32nd Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary
  • 4Egis Pharmaceutical Ltd, Budapest, Hungary
  • 5Richter Gedeon Ltd, Budapest, Hungary
  • 6Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
  • 7 Department of Molecular Pathology Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
Further Information

Publication History

Received 9 April 2003

Accepted after second revision 6 October 2003

Publication Date:
01 April 2004 (online)

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Abstract

Free radicals are involved in several pathological processes in living organisms, for example in athero- and oncogenesis. Some steroids are known to be effective antioxidants, while others do not play any such role. The aim of our study was to examine the antioxidant capability of different metabolites in the synthesis of steroid hormones. As a model, we chose human neutrophils producing superoxide anion, which is the source of many other radicals. Neutrophils were separated from healthy volunteers. Isolated cells were incubated with varying concentrations of steroid compounds and stimulated with N-formyl-Met-Leu-Phe. Superoxide anion production was determined by photometry. Neutrophils incubated with corticosterone and 18-hydroxy-deoxycorticosterone showed a significant reduction in superoxide production, whereas we found a significant enhancement in the presence of 11β-hydroxyprogesterone. Furthermore, we observed a non-significant decreasing trend after incubation with cholesterol 3-sulphate and an increasing tendency using 11-hydroxyandrostenedione. We were also able to produce newer morphological and functional evidence of the role of myeloperoxidase enzyme in the steroidal antioxidant effect by electronic microscopy and use of sodium hypochlorite in our incubation model. Based on these results, we conclude that not only steroid end products but also their intermediate metabolites, most of which are also present in human plasma, partly influence free radical metabolism. Thus, this study provides further argument for the search for the molecular basis responsible for the antioxidant effect of steroid structures. This may lead to new opportunities for finding really efficient antioxidants, which might perhaps be used in a combined manner with other agents in the fight against certain life-threatening diseases.

Key words

Free radicals - Steroid metabolites - Antioxidants

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G. Békési, M. D.

2nd Dept. of Medicine, Semmelweis University

Szentkirályi u. 46 · 1088 Budapest · Hungary

Phone: +36(30)9324008

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Email: dani86@vnet.hu