Seminal plasma does not aid in the transport of phenolsulfonphthalein across the uterotubal junction in mares.

This study tested the hypothesis that the presence of prostaglandin E2 in seminal plasma would aid in the transport of phenolsulfonphthalein (PSP) across the uterotubal junction. Five mares in estrus were inseminated during estrus with PSP dissolved in phosphate-buffered saline and during the subsequent estrus with PSP added to a standard insemination dose. Serum and urine samples were obtained at hours 0, 1, 2, and 3 following treatment and examined for the presence of PSP. Phenolsulfonphthalein could not be detected in any of the urine samples collected from mares following either treatment. None of the serum samples collected following intrauterine installation of PSP in PBS contained PSP. Phenolsulfonphthalein was detected in serum samples from 1 mare following insemination with semen containing PSP. Components in seminal plasma such as PGE2 did not facilitate the transport of PSP across the uterotubal junction as had been hypothesized.

Le plasma séminal ne facilite pas le transport de la phénolsulfonphtaléine au travers de la jonction utéro-tubaire des juments. Cette étude a testé l'hypothèse voulant que la présence de la prostaglandine E2 dans le plasma séminal facilite le transport de la phénolsulfonphtaléine (PSP) au travers de la jonction utéro-tubaire. Cinq juments en oestrus ont été inséminées avec de la PSP dissoute dans une solution saline tamponnée au phosphate et, durant l'oestrus subséquent, avec de la PSP ajoutée à une dose d'insémination standard. Des prélèvements de sérum et d'urine ont été obtenus aux heures 0, 1, 2 et 3 ainsi qu'après le traitement et examinés pour déceler la présence de la PSP. La phénolsulfonphtaléine n'a pas pu être détectée dans aucun des échantillons d'urine prélevés auprès des juments après l'un ou l'autre des traitements. Aucun des échantillons de sérum prélevés après l'installation intra-utérine de la PSP dans PBS ne contenait de PSP. La phénolsulfonphtaléine a été détectée dans des échantillons de sérum provenant d'une jument après l'insémination avec du sperme contenant de la PSP. Des composants dans le plasma séminal comme le PGE2 n'ont pas facilité le transport de la PSP au travers de la jonction utéro-tubaire conformément à l'hypothèse émise.(Traduit par Isabelle Vallières).

Phenolphthalein metabolite inhibits catechol-O-methyltransferase-mediated metabolism of catechol estrogens: a possible mechanism for carcinogenicity.

Phenolphthalein (PT), used in over-the-counter laxatives, has recently been identified as a multisite carcinogen in rodents, but the molecular species responsible for the carcinogenicity is not known. A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s. The above data, when taken together, suggest that chronic administration of PT may enhance metabolic redox cycling of both PT-CAT and the catechol estrogens and this, in turn, may contribute to PT-induced tumorigenesis.

Elevation of beta-glucuronidase activity in medicated patients with epilepsy.

Elevations of serum beta-glucuronidase (GRS) enzyme activity can occur under a variety of pathological conditions. Using phenolphthalein glucuronic acid as the substrate, 158 epileptic patients were randomly screened for GRS. GRS was distinctly elevated (65.9 +/- 30.0 micrograms phenolphthalein/ml serum) in patients, compared with the normal group (27.0 +/- 10.0). No difference in GRS levels were found when seizure-free (greater than 1 year) patients (n = 61; GRS, 62.6 +/- 32.7 micrograms) were compared with patients who had seizure episodes within 1 week (n = 26; GRS, 73.2 +/- 24.9 micrograms), and there were no differences when intermediate groups were examined. GRS elevations were found to be linearly and directly correlated with free phenytoin ultrafiltrate levels (n = 35, r = 0.7692, p less than 0.0001) when patients were co-medicated with valproic acid, with serum phenobarbital levels (n = 58, r = 0.5361, p less than 0.05), with serum valproic acid levels (n = 43, r = 0.3173, p less than 0.05), and with the sum of serum phenobarbital and valproic acid levels (n = 16, r = 0.8657, p less than 0.0001). The findings indicate that GRS elevations are probably due to anticonvulsant medications rather than to the frequency of seizures. There is no evidence that GRS determinations can be used for the diagnosis or prognosis of patients with epilepsy.

[Clinico-biochemical study of experimental renal injuries in rats. 3. Relations between serum half-life of phenolsulfonphthalein and renal injuries].

The serum half-life of PSP(PSP t/2) was determined in normal and nephropathy rats by repeated blood collection under an unanesthetized condition to estimate its usefulness as a renal functional parameter. In normal rats, the serum disappearance curve of PSP (5 mg/kg) could be resolved into two exponential components, and the mean PSP t/2 in the second component was 12 min (n=100). About 71% of the PSP loaded was excreted in urine and 19% in bile. A single subcutaneous injection of HgCl2 delayed the serum disappearance of PSP and simultaneously decreased its urinary excretion and increased its biliary excretion. The serum protein binding ratio of PSP became higher when the serum concentration of PSP was decreased, while it became lower when the serum albumin level was decreased. PSP t/2 in rats treated with gentamicin or puromycin amino-nucleoside as well as that in rats given HgCl2 was increased in correlation with changes in common renal functional parameters such as serum urea nitrogen, serum creatinine, urinary protein and morphologic changes of the kidney. Masugi-type nephritis rats showed no change in PSP t/2. Moreover, PSP t/2 was well correlated with the maximal tubular secretion rate of p-amino-hippuric acid. Since PSP t/2 can be determined periodically on the same animal, it is considered to have effective application as a renal functional test in rats, especially for examining tubular secretion.

Simultaneous assay of bromosulfophthalein and phenolsulfonphthalein in the blood as a test of hepatic and renal functional capacity.

A spectrophotometric procedure for the assay of bromosulfophthalein and phenolsulfonphthalein in the plasma of various animal species and the half-life of the two dyes in plasma representing respectively the rate of liver depuration and that of kidney depuration are described. The method is easy to execute and lends itself particularly well for the simultaneous assessment of hepatic and renal function in the same animal.

A pharmacokinetic model for enterohepatic recirculation in the rat: phenolphthalein, a model drug.

A classical compartmental pharmacokinetic model was developed to describe the systemic blood concentration-time profile of phenolphthalein and its glucuronide conjugate (total 3H) following a single intravenous bolus injection of [3H]phenolphthalein. The model incorporates a biliary transport system, including a finite lag time for the biliary phenophthalein glucuronide to be hydrolyzed in the intestine before absorption. Data obtained from bile duct-cannulated animals were fit to the same model excluding any component for intestinal absorption. Agreement between the rate constants obtained for both fits indicates that the model is internally consistent. The model was then used to simulate a 24-hour time-course of phenolphthalein-equivalent blood concentrations which indicates that the long apparent half-lives calculated during this period are artifacts of recirculation.

[Investigations of changes in the phenolsulphonphthalein plasma levels in pregnant women with EPH syndrome (author's transl)]. / Untersuchungen über Veränderungen des Phenolsulfonphthalein-Plasmaspiegels bei Graviden mit EPH-Syndrom

In 53 patients, 24 healthy pregnant women and 29 patients with EPH (edema, proteinuria, hypertension) syndrome, the intravenous phenolsulphonphthalein test was performed between the 32nd and 42 weeks of pregnancy. At the same time, the serum creatinine and estrogen excretion in the 24 hour urine were determined. According to this, normal pregnancy and also pregnancies with one or more symptoms of the EPH syndrome without raised blood pressure do not cause changes of the PSP plasma level. A statistically significant rise in the PSP plasma level is only found with a blood pressure of 140/90 mm Hg, and simultaneously a close correlation to the estrogen excretion in the urine (r = -0.4) and the blood pressure (r = 0.6). Estrogen excretion is reduced with increasing blood pressure (r = -0.75). No correlation could be established between the PSP serum level and the creatinine in the serum.