Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro.
The preparation of suspensions of porcine adrenocortical cells is described. Within the conditions adopted, the cell suspension responded to various agents as expected. It was possible to screen drugs (standard range 0.3-100 microM, incubation period 1 h) for actions on the production/release of aldosterone by the cortical cells using 1 microM deoxycorticosterone as substrate. Progesterone, pregnenolone or corticosterone were also used as substrates. Feed additives of the quinoxaline type induced a slowly developing inhibition of aldosterone production/release by the cell suspension, which was virtually irreversible. During the standard 1 h incubation period inhibitions of up to 22 +/- 2% of control were observed, which increased upon prolongation of the incubation by 2 h. With 100 microM cyadox the inhibition increased from 19 +/- 2% to 35 +/- 2% with prolonged incubation. Ten nitrofuran compounds exerted a more rapidly developing inhibition (by up to 79 +/- 1% of control) of aldosterone production/release, which was reversible. A submaximal inhibition with 10 microM furazolidone of 21 +/- 5% increased to 40 +/- 1% with longer incubation. The concentrations at which these compounds exerted this effect in vitro were well below the peak blood plasma concentrations encountered after administration of the drugs in therapeutic doses. Polyether-antibacterials/ionophores rapidly inhibited aldosterone production/release (to 26 +/- 1% of control) and this effect was completely reversible. The nitroimidazole compounds tested did not affect aldosterone production/release when deoxycorticosterone or progesterone were used as substrates. With use of corticosterone and to a lesser extent with pregnenolone as substrates a clear inhibition (to 73 +/- 3% of control) of aldosterone production was obtained. Amprolium in concentrations up to 100 microM, with deoxycorticosterone as substrate, did not induce a significant change in aldosterone production/release by the suspension of adrenocortical cells. In the same dose range tylosin and roxarsone induced a small but significant inhibition (by up to 10 +/- 3% of control) of aldosterone production/release, which was not dose-dependent. It is concluded that a wide range of growth-promoting drugs may be able to change aldosterone production/release in the animal.
Jager
L P
LP
DLO-Central Veterinary Institute (CDI-DLO), Department of Biochemistry and Toxicology, Lelystad, The Netherlands.
De Graaf
G J
GJ
Widjaja-Greefkes
H C
HC
Accord-Burleson
C C
CC
Van den Dungen
H M
HM
Baars
A J
AJ
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005503:Food Additives / Q000494:pharmacology*; D066298:In Vitro Techniques; D009581:Nitrofurans / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011863:Radioimmunoassay / Q000662:veterinary; D013552:Swine
D000900:Anti-Bacterial Agents; D005503:Food Additives; D009581:Nitrofurans; D009593:Nitroimidazoles; D011810:Quinoxalines; D000450:Aldosterone