ABSTRACT
BACKGROUND: The three chemical ultraviolet absorbers benzophenone-3 (BP-3), octyl-methoxycinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC) are commercially used in sunscreens worldwide. Apart from sun protection, they may possess endocrine-disrupting effects in animals and in vitro. For all three compounds, only sporadic measurements of percutaneous absorption and excretion after topical application in humans have been described. METHODS: In this study, 32 healthy volunteers, 15 young males and 17 postmenopausal females, were exposed to daily whole-body topical application of 2 mg/cm(2) of sunscreen formulation at 10% (w/w) of each for 4 days. Blood concentrations were measured at 0, 1, 2, 3, 4, 24 and 96 h and urine concentrations at 0, 24, 48, 72 and 96 h. RESULTS: Almost all three sunscreens were undetectable in plasma and urine before the first application. One to 2 h after the first application, all three sunscreens were detectable in plasma. The maximum median plasma concentrations were 187 ng/mL BP-3, 16 ng/mL 4-MBC and 7 ng/mL OMC for females and 238 ng/mL BP-3, 18 ng/mL 4-MBC and 16 ng/mL OMC for men. In the females, urine levels of 44 ng/mL BP-3 and 4 ng/mL of 4-MBC and 6 ng/mL OMC were found, and in the males, urine levels of 81 ng/mL BP-3, 4 ng/mL of 4-MBC and OMC were found. In plasma, the 96-h median concentrations were higher compared with the 24-h concentrations for 4-MBC and OMC in men and for BP-3 and 4-MBC in females.
Subject(s)
Sunscreening Agents/pharmacokinetics , Administration, Topical , Adult , Aged , Aged, 80 and over , Benzophenones/blood , Benzophenones/urine , Camphor/analogs & derivatives , Camphor/blood , Camphor/urine , Chromatography, High Pressure Liquid , Cinnamates/blood , Cinnamates/urine , Female , Humans , Male , Middle Aged , Postmenopause , Skin Absorption , Statistics, NonparametricSubject(s)
Sunscreening Agents/pharmacokinetics , Thyroid Hormones/blood , Thyrotropin/blood , Administration, Topical , Adult , Aged , Aged, 80 and over , Animals , Benzophenones/administration & dosage , Benzophenones/pharmacokinetics , Camphor/administration & dosage , Camphor/analogs & derivatives , Camphor/pharmacokinetics , Cinnamates/administration & dosage , Cinnamates/pharmacokinetics , Female , Humans , Male , Middle Aged , Rats , Single-Blind Method , Sunscreening Agents/administration & dosageABSTRACT
Liver cirrhosis is a chronic disease associated with sodium retention due to increased tubular sodium reabsorption. However, the exact tubular site of increased sodium reabsorption in uncertain. We have recently demonstrated selective hypertrophy of the inner stripe of the outer medulla (ISOM) in rats with liver cirrhosis induced by common bile duct ligation (CBL). The present study was designed in order to measure Na-K-ATPase activity in the two major tubular segments located in the ISOM: the thick ascending limb of henles (MTAL) and the collecting ducts (OMCD) in CBL rats. Sham-operated rats were used as controls. In addition, the natriuretic response to amiloride (0.2 mg kg(-1) h(-1) i.v) was examined in conscious, chronically instrumented rats during conditions where amiloride-induced volume losses were replaced continuously using a servo-controlled i.v. volume replacement system. For 4-5 weeks after CBL, cirrhotic rats showed sodium retention relative to control rats without any sign of ascites. Plasma levels of sodium and aldosterone were normal, but plasma vasopressin was increased. Effective renal plasma flow was significantly increased, whereas glomerular filtration rate (GFR) and renal lithium handling were normal. The CBL rats showed a blunted natriuretic response to amiloride (DeltaFE(Na): 1.17 +/- 0.15% vs. 1.65 +/- 0.13%; P < 0.05). In rats with CBL, Na-K-ATPase activity per mm tubular length was decreased in the OMCD and unchanged in the TAL segment. These results suggest that increased tubular sodium reabsorption in liver cirrhotic rats with early sodium retention is localized in segments proximal to the collecting ducts.
Subject(s)
Kidney Tubules, Collecting/metabolism , Liver Cirrhosis, Experimental/physiopathology , Loop of Henle/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Sodium/metabolism , Amiloride/pharmacology , Animals , Female , Kidney Tubules, Collecting/drug effects , Liver Cirrhosis, Experimental/metabolism , Loop of Henle/drug effects , Models, Biological , Models, Chemical , Natriuresis/drug effects , Rats , Reference Values , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The mechanisms underlying the acute antidiuretic response to bendroflumethiazide (BFTZ; 0.25 mg/h for 3 h) in rats with nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumented female Wistar rats either by chronic lithium administration (40-60 mmol Li/kg of diet for 4 weeks) or by acute infusion of V2 antagonist OPC-31260 (0.2 mg/h). Renal clearance experiments were performed in conscious rats instrumented with permanent catheters. During experiments total body water content was held constant by i.v. replacement of urine production (V) with 150 mM glucose. One group in addition received i.v. replacement of urinary sodium losses. In both models of NDI, BFTZ-induced antidiuresis was associated with a decrease in the delivery of tubular fluid to the distal nephron, as measured by lithium clearance (C(Li)). Both the antidiuresis and the decrease in C(Li) could be prevented by sodium replacement. BFTZ did not affect distal water handling as measured by V/C(Li). BFTZ did not induce antidiuresis in normal rats with water diuresis. It is concluded that in rats with NDI, thiazide-induced antidiuresis can be entirely explained by a fall in distal delivery of tubular fluid related to sodium depletion. This contrasts the response in rats with central diabetes insipidus, where thiazides in addition increase distal water reabsorption.