Carbadox-induced inhibition of aldosterone production in porcine adrenals in vitro

Spierenburg, Th. J.; Baars, A.J.; Graaf, G. J. de; Jager, L. P.

doi:10.1016/0887-2333(88)90026-4

Cited by 14 publications

(5 citation statements)

References 5 publications

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“…, 1990). Carbadox has led to inhibition of aldosterone production by pig adrenal preparations in in vitro studies (Spierenburg et al. , 1988).…”

Section: Introductionmentioning

confidence: 99%

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Woodward¹

2005

Vet Pharm & Therapeutics

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Toxicological studies are conducted on constituents of veterinary medicinal products for a number of reasons. Aside from being a requirement of legislation, they are carried out for predictive purposes in the assessment of user safety or for the determination of consumer safety, for example, in the elaboration of maximum residue limits or tolerances. Alternatively, the results of toxicology studies may be available as they have been generated for registration of the drug for human medicinal purposes. This paper examines if the results of such studies have any predictive value for adverse reactions, which might occur during clinical use in animals. A number of adverse reactions, notably the Type A (toxicology or pharmacology dependent) should be predictable from these laboratory studies. However, as with human pharmaceutical products, they have less utility in predicting Type-B reactions (idiosyncratic in nature).

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“…, 1990). Carbadox has led to inhibition of aldosterone production by pig adrenal preparations in in vitro studies (Spierenburg et al. , 1988).…”

Section: Introductionmentioning

confidence: 99%

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Woodward¹

2005

Vet Pharm & Therapeutics

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“…1984). To explain this potentiation, it was suggested that furazolidone enhances the uptake of carbadox from the intestines (Graaf et al. 1988).…”

Section: Discussionmentioning

confidence: 99%

Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro

Jager¹,

Graaf²,

Widjaja-Greefkes³

et al. 1994

Vet Pharm & Therapeutics

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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.

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“…Spierenburg et al investigated that the carbadox had the ability to inhibition of aldosterone production by pig adrenal slices. A dose dependent decrease in aldosterone production was reported at the 1~40 µg/ml [55]. In a study using a suspension of porcine adrenocortical cells, QdNOs were found to reduce the output of aldosterone.…”

Section: Evidences Of Quinoxaline 1 4-dioxides In Aldosterone Producmentioning

confidence: 94%

“…It's demonstrated that a complex crosstalk between ROS-generating system and aldosterone secretion. The induction of oxidative stress following exposure to mequindox (MEQ) could result in a membrane damage and dysfunction of adrenal mitochondrion, and then cause the contents loss of steroid hormone including CYP11A1, CYP11B1 and CYP11B2, finally leading to the deregulation of steroid hormone secretion and unbalance of ion concentration [55]. Moreover, Higher doses of MEQ showed similar depressive responsibility for most of renin-angiotensin-aldosterone system (RAAS) components in adrenal and kidney, indicating a down-regulation of both intra-and extra-RAAS, the upstream of aldosterone production [58].…”

Section: Evidences Of Quinoxaline 1 4-dioxides In Aldosterone Producmentioning

confidence: 99%

“…The endocrinological effects of these compounds have long been recognized. Besides their influence on metabolic hormones and epidermal growth factor in swine [17] QdNOs such as carbadox and its major metabolites induced a special decline of aldosterone production from the adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia [18][19][20][21] Aldosterone is a steroid hormone and the most important mineralocorticoid in the human body. Clinically, excess aldosterone is associated with increased stroke risk [22]; progressive renal disease [23], higher morbidity and mortality in cardiovascular diseases such as myocardial infarction (MI) and heart failure (HF) [24][25].…”

Section: Introductionmentioning

confidence: 99%

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Potential benefits of quinoxaline 1, 4-dioxides in aldosterone dysmetabolism disease—A medical hypothesis

Zou¹,

Zheng²,

Huang³

et al. 2011

OJAS

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Quinoxaline 1, 4-dioxides (QdNOs) are quinoxaline derivatives which have been used as antimicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, antitubercular and inhibiting parasite. QdNOs such as carbadox and their major metabolites induced a special decline of aldosterone production from the swine adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia. This can also be expected to be the case for human. As a mainly physiological hormone and a novel steroid with potent mineralocorticoid activity, aldosterone plays an important role in the pathophysiological process of brain, renal and heart disease progression and may be a renal and vascular risk factor. Here, we provide evidence to support the hypothesis that QdNOs may lead potential benefits in aldosterone dysmetabolism disease via the synthesis deficiency of aldosterone in adrenal and/or the cardiovascular tissues. If the hypothesis is true, it may provide a new option into the therapy for aldosterone dysmetabolism disease, especially in cardiovascular system, and thus assume a broader application of QdNOs.

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Carbadox-induced inhibition of aldosterone production in porcine adrenals in vitro

Cited by 14 publications

References 5 publications

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro

Potential benefits of quinoxaline 1, 4-dioxides in aldosterone dysmetabolism disease—A medical hypothesis

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