Differential effects of nitrofurans on the production/release of steroid hormones by porcine adrenocortical cells in vitro.
Changes in the biogenesis of corticosteroids caused by nitrofurans were studied. The three nitrofurans used: furazolidone, furaltadone and nitrofurantoin, altered the steroid production/release by porcine adrenocortical cells in vitro during 1 h incubations. With pregnenolone as a substrate the nitrofurans inhibited aldosterone production/release. Although the nitrofurans differed in potency (nitrofurantoin > furazolidone > furaltadone) maximum inhibition occurred at 100 microM. In this concentration the nitrofurans changed also the release/production of other corticosteroids. The output of corticosterone and cortisol decreased by 50%. The production/release of deoxycortisol stayed the same. In contrast the output of progesterone and 17alpha-hydroxyprogesterone increased to more than 200% of control. The nitrofurans slightly reduced the output of androstenedione. No significant increases of the production/release of other steroids (testosterone, dehydroepiandrosterone, estradiol-17beta and estrone) by the cell suspension could be observed. The profile of the nitrofuran-induced changes lead to the conclusion that nitrofurans interfere with mitochondrial enzymes. These enzymes, presumably cytochrome P450(11,18) mediate the hydroxylation and the oxidation at C11 and C18, the final steps in the biogenesis of aldosterone, corticosterone and cortisol. The rapid and reversible fall in the output of these steroids occurs in vitro at concentrations which are below therapeutic blood concentrations seen in vivo. At higher concentrations the nitrofurans hinder the biogenesis of androgens. Thus nitrofurans can also affect steps in the steroid biogenesis located in the endoplasmatic reticulum.
Jager
L P
LP
D.L.O.-Central Veterinary Institute (CDI-DLO), Department of Biochemistry and Toxicology, Lelystad, The Netherlands. in%l.p.jager@id.dlo.nl
de Graaf
G J
GJ
Widjaja-Greefkes
H C
HC
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005664:Furazolidone / Q000494:pharmacology; D009581:Nitrofurans / Q000494:pharmacology*; D009582:Nitrofurantoin / Q000494:pharmacology; D023303:Oxazolidinones; D011810:Quinoxalines / Q000494:pharmacology; D013256:Steroids / Q000096:biosynthesis* / Q000378:metabolism; D013552:Swine
D000892:Anti-Infective Agents, Urinary; D009581:Nitrofurans; D023303:Oxazolidinones; D011810:Quinoxalines; D013256:Steroids; D005664:Furazolidone; C007795:furaltadon; D009582:Nitrofurantoin