Systematic investigation of different steroid precursors with respect to their effect on superoxide anion production by human neutrophil granulocytes.
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 11beta-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.
Békési
G
G
2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
Rácz
K
K
Hrabák
A
A
Kakucs
R
R
Várbíró
S
S
Magyar
Z
Z
Fehér
J
J
Dinya
E
E
Pázmány
T
T
Paku
S
S
Székács
B
B
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology; D002788:Cholesterol Esters / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009195:Peroxidase / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000975:Antioxidants; D002788:Cholesterol Esters; D011355:Prodrugs; D013256:Steroids; D013481:Superoxides; C042509:18-hydroxydeoxycorticosterone; D003900:Desoxycorticosterone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; C007045:cholesteryl sulfate; D003345:Corticosterone