The effects of drugs and chemicals upon the structure of the adrenal gland

RIBELIN, W

doi:10.1016/0272-0590(84)90224-0

Cited by 109 publications

(34 citation statements)

References 49 publications

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“…Proliferative changes of the rat adrenal medulla have been reported to be produced by numerous chemicals that are devoid of similar actions in humans (nicotine, reserpine, lactose, sorbitol, xylitol, and lactilol) (Ribelin, 1984;Roe and Bar, 1985;Boelsterli and Zbinden, 1985). The preponderance of evidence indicates that most, if not all, of these agents cause medullary hyperplasia in the rat adrenal through indirect and physiologically explainable mechanisms such as the production of hormonal imbalances, chemically induced changes in general nutritional status, and changes in calcium homeostasis (Gopinath et al, 1987;Roe and Bar, 1985;Tischler and DeLellis, 1988).…”

Section: Discussionmentioning

confidence: 99%

Toxicology and carcinogenesis studies of dietary titanium dioxide‐coated mica in male and female Fischer 344 rats

Bernard¹,

Osheroff²,

Hofmann

et al. 1990

Journal of Toxicology and Environmental Health

114

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Male and female Fischer 344 rats were fed diets containing 0, 1.0, 2.0, or 5.0% titanium dioxide (TiO2) coated mica for up to 130 wk. This dosage regimen produced no consistent or biologically important changes in survival, body weight gains, hematologic or clinical chemistry parameters or histopathology. Under the conditions of this 130 wk feeding study there was no evidence that TiO2-coated mica produced either toxicologic or carcinogenic effects at dietary concentrations as high as 5.0%. The results suggest that dietary exposure to TiO2-coated mica does not pose a significant human health hazard.

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Section: Discussionmentioning

confidence: 99%

Toxicology and carcinogenesis studies of dietary titanium dioxide‐coated mica in male and female Fischer 344 rats

Bernard¹,

Osheroff²,

Hofmann

et al. 1990

Journal of Toxicology and Environmental Health

114

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“…Owing to its high blood ½ow per unit mass, high lipophilicity and presence of enzymes with metabolizing potential, the adrenal is the endocrine organ that is the most vulnerable to toxic insult (Hinson and Raven, 2006;Ribelin, 1984). Suppression of adrenocortical function and steroidogenesis may have fatal consequences, as demonstrated by etomidate.…”

Section: Introductionmentioning

confidence: 99%

Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption — screening of 30 selected chemicals in the human H295R cell model

Ullerås

Ohlsson

Oskarsson

2008

J of Applied Toxicology

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The adrenal gland is a vulnerable target for toxic insult. Disruption of adrenal steroidogenesis and hormone secretion may cause serious effects on human health. A human in vitro model is needed to predict effects, and elucidate mechanisms of endocrine disruption and adrenal toxicity. The human adrenocortical cell line H295R has been used to screen for effects on sex hormones. Here, we have analyzed the effect of 30 potential endocrine disrupting chemicals on the secretion of cortisol and aldosterone from the H295R cells, using specific ELISA assays. The effect of chemicals was analyzed for basal and forskolin- or angiotensin II-stimulated hormone secretion. The chemicals were tested at the highest concentration where they displayed no evident unspecific cytotoxicity. Quantitative and qualitative differences in effects on hormone secretion were demonstrated for the various chemicals. A subset of the chemicals displayed different effects on cortisol and aldosterone secretion, and in some cases the effects were different between basal and stimulated hormone secretion. Aminoglutethimide, prochloraz, ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the most marked inhibitory effects on cortisol (with or without forskolin) and ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the most marked effects on aldosterone (with or without angiotensin II). The results are discussed in terms of known effects, structural similarity and possible mechanisms. We have shown that adrenal steroidogenesis is a vulnerable target for toxic insult and that the H295R assay is a useful in vitro model for screening purposes.

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“…The physiological role of the adrenal cortex can also hide expression of toxicity which may only become apparent when significant activation of the stress response is required to tolerate trauma and crises and assist survival. The lack of standardised adrenocortical functional testing is considered a major deficiency in regulatory endocrine disrupter strategies (see [2,3,59]) and more surprising given that the adrenal is the most common toxicological target in the endocrine system [4] its role as a vital organ and in developmental processes. Further, the tendency to "write-off" adrenal findings as stress in mammalian regulatory toxicology studies, in the absence of corroboratory evidence of adrenocortical functionality, is common and potentially dangerous which requires recognition in regulatory toxicology.…”

Section: Resultsmentioning

confidence: 99%

“…The adrenal gland is the most commonly affected endocrine organ in toxicology studies [4]. Part of the reason for this is the central physiological role of the adrenal in the stress response, where toxic insult from the administration of drugs and chemicals administered at the maximum tolerated dose is often stressful and activates the hypothalamo-pituitary-adrenocortical (HPA) axis to increase ACTH secretion.…”

Section: Characteristics Of the Adrenal Gland Conveying Vulnerabilitymentioning

confidence: 99%

“…mammary, uterus, prostate, etc.). The problem arises in how to interpret toxicopathological changes in these non reproductive endocrine organs, particularly the adrenal as the most common toxicological target in the endocrine system [4], without additional supportive mechanistic studies. A particular weakness has centred on the interpretation of the most commonly observed change in the adrenal namely adrenal (adrenocortical) hypertrophy.…”

Section: Introductionmentioning

confidence: 99%

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