INTRODUCTION: The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) oxidizes cortisol to inactive cortisone. Its congenital absence or inhibition by licorice increases cortisol levels at the mineralocorticoid receptor, causing mineralocorticoid effects. We tested the hypothesis that flavonoids found in grapefruit juice inhibit this enzyme in vitro and that grapefruit juice itself inhibits it in vivo. METHODS: Microsomes from guinea pig kidney cortex were incubated with cortisol and nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) and different flavonoids and the oxidation to cortisone measured with use of HPLC analysis. In addition, healthy human volunteers drank grapefruit juice, and the ratio of cortisone to cortisol in their urine was measured by HPLC and used as an index of endogenous enzyme activity. RESULTS: Both forms of 11 beta-OHSD requiring either NAD or NADP were inhibited in a concentration-dependent manner by the flavonoids in grapefruit juice. Normal men who drank grapefruit juice had a fall in their urinary cortisone/cortisol ratio, suggesting in vivo inhibition of the enzyme. CONCLUSION: Dietary flavonoids can inhibit this enzyme and, at high doses, may cause an apparent mineralocorticoid effect.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1996

Publication and proprietary information.

Explore the source record for details and available documents.

Periodicals as Topic↗

PubMed1995

Clinical pharmacology.

The issue of what drug effects to measure, surrogate end points, has been emphasized by two recent clinical trials. Several recent studies have given us new information about why different people react so differently to the same dose of the same medicine.

Humans↗

PubMed1995

Cortisol metabolism in hypertensive patients who do and do not develop hypokalemia from diuretics.

Deficiency of 11 beta-hydroxysteroid dehydrogenase causes hypertension and hypokalemia. To test whether hypertensive patients who develop hypokalemia when treated with diuretics have low levels of activity of this enzyme as a metabolic predisposition to the development of hypokalemia, we measured urinary cortisone, cortisol, tetrahydrocortisol, tetrahydrocortisone, and creatinine in 42 hypertensive patients who either did or did not become hypokalemic on hydrochlorothiazide. The mean ratios of cortisone to cortisol, tetrahydrocortisone to tetrahydrocortisol, tetrahydrocortisol to cortisol, and cortisol to creatinine did not differ between the two groups. We conclude that hypertensives who develop hypokalemia on diuretics do not have low activity of this enzyme. They also do not appear to have low ring A reduction or higher cortisol secretion rates compared with hypertensives who do not develop hypokalemia. We failed to find a metabolic predisposition to the development of hypokalemia by diuretic treatment.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1995

Slight renal effect of mercury from amalgam fillings.

The current study was to answer the question: Is enough mercury absorbed from dental amalgam fillings to produce renal damage? One hundred healthy adults (18-44 years old) filled out health questionnaires and voided urine samples. Urine mercury concentration and N-acetyl-beta-glucosaminidase (NAG) were measured. Subjects were grouped into those having amalgam fillings (N = 66) and those without (N = 34). Median (95% Confidence Interval) urine mercury was 1 (1-2) and 0 (0-0.6) ng/ml (P < 0.01) and median urine NAG was 23 (18-27) and 16 (11-18) units (P < 0.05) in the two groups respectively. People with mercury amalgam fillings excreted slightly more mercury than people without them, and have a very small increase in urinary NAG excretion that is probably of no clinical significance. This dose of mercury absorbed from amalgam appears to be too little to be a public health hazard for renal injury.

Acetylglucosaminidase↗

PubMed1994

Shingles, allergies, family medical history, oral contraceptives, and other potential risk factors for systemic lupus erythematosus.

The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.

Adult↗

PubMed1994

Breast silicone implants and risk of systemic lupus erythematosus.

The uncertain safety of breast implants has been a major controversy of late, both in the lay press and in the scientific literature. A case-control study had been performed in the Philadelphia metropolitan area during 1985-1987 to investigate potential risk factors for systemic lupus erythematosus (SLE). A total of 219 eligible cases who met the American Rheumatism Association criteria for SLE were identified from the medical practices of cooperating rheumatologists in the area; 195 (89%) of these were enrolled in the study. Friends of the cases, matched to the cases on sex and age (+/- 5 years) served as controls. For the current investigation, conducted during June 1992 through September 1992, we attempted to re-contact each of these individuals. Using a short telephone interview, we asked each subject to provide information on any surgery that they may have had prior to the index date, i.e. the year of diagnosis of SLE in the cases and the same year for the age-matched friend controls. Specific questions were asked about plastic surgery in general and breast implants in particular. 148 (75.9%) of the 195 SLE cases being sought and 111 (77.6%) of the 143 controls being sought agreed to be re-interviewed for this study. Only 1 (0.8%) out of 133 female SLE cases reported having had a breast implant, 8 years prior to the diagnosis of SLE. This compared to 0 out of the 100 female friend controls (Fisher exact one-tailed p-value = 0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Implants↗

PubMed1994

Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds.

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) can cause excess mineralocorticoid effects and hypokalemia. Several substances causing hypokalemia (glycyrrhizic acid in licorice and gossypol) inhibit this enzyme. We tested other compounds for activity to inhibit 11 beta-OHSD in guinea pig kidney cortex microsomes with NADP as cofactor and cortisol as substrate. Furosemide was an inhibitor while bumetanide was not, indicating a mechanism for the increase K+ excretion caused by furosemide compared with bumetanide. Naringenin (found in grapefruit juice), ethacrynic acid, and chenodeoxycholic acid had inhibitor IC50 values similar to glycyrrhizic acid. We conclude that various compounds can inhibit this enzyme and may play a role in K+ metabolism and adrenocorticosteroid action.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1994