Antioxidant effect of the active metabolites of tibolone.

Certain steroidal compounds have an antioxidant effect in humans. Our aim was to test whether the synthetic steroid tibolone and its metabolites are also able to display such a property. For this, granulocytes from healthy men and women were incubated for two hours with different concentrations (10(-7), 10(-8), 10(-9 )M) of either estradiol, tibolone, 3α-hydroxytibolone, 3ß-hydroxytibolone, Δ(4)-tibolone, 3α-sulfated-tibolone, 3α-17ß-disulfated-tibolone, 3ß-sulfated-tibolone or 3ß-17ß-disulfated-tibolone. Superoxide anion generation of neutrophils was measured by photometry. Results of different steroids were given as percentages of their controls. A more simple superoxide generating system, the xanthine-xanthine oxidase reaction was also tested. We found that granulocyte superoxide production did not differ from the control using 10(-9 )M of steroids. Using 10(-8 )M concentration: estradiol (80.9 ± 2.5%); 3ß-sulfated-tibolone (83.3 ± 4.7%); 3ß-17ß-disulfated-tibolone (81.0 ± 4.2%) caused a significant decrease in superoxide production, compared to the control. In addition at 10(-7 )M, 3ß-hydroxytibolone and 3α-sulfated-tibolone also showed antioxidant effects. In the xanthine-xanthine oxidase system estradiol (67.4 ± 1.0%), 3α-sulfated-tibolone (85.8 ± 5.3%), 3α-17ß-disulfated-tibolone (71.9 ± 2.5%), 3ß-sulfated-tibolone (73.9 ± 5.0%), and 3ß-17ß-disulfated-tibolone (65.8 ± 3.4%) caused a significant decrease in superoxide production. Conclusively, although tibolone itself did not show significant antioxidant capacity, most of its active metabolites have antioxidant effects.

The effect of certain steroid hormones on the expression of genes involved in the metabolism of free radicals.

Steroid hormones influence the antioxidant processes of cells. However, the molecular mechanism of this effect is not fully clear. Our aim was to examine how steroid hormones affect the expression of certain genes that play a role in antioxidant processes. Blood was taken from ten healthy volunteers. Neutrophil granulocytes were separated and treated either with 17-ß-estradiol, progesterone, testosterone, or cortisol. Whole RNA was isolated and reverse transcription was carried out in treated and control groups. Relative quantification was performed with SYBR Green assay and gene-specific oligonucleotides. We found that the expression of Mn-superoxide dismutase was significantly increased by 17-ß-estradiol and testosterone, myeloperoxidase expression was significantly elevated by cortisol and progesterone, and the expression of NADPH oxidase was significantly decreased by progesterone. We conclude that the antioxidant effect of steroid hormones is in part carried out through transcriptional regulation of certain enzymes. Subsequent studies are required in order to examine the non-genomic, membrane receptor mediated effect of steroids on antioxidant processes.

The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model.

Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague-Dawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet + selegiline and (4) normal rat food + selegiline. Selegiline solution (2.5 µg/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20-30 ml/day), the daily dose was roughly equal with that used in the human therapy (5-10 mg/day). TSC was determined both at the beginning (0 day) and at the end of the study (28 days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers.

[Successful surgical removal of adrenocortical carcinoma growing into the inferior vena cava and the right atrium]. / A vena cava inferioron keresztül a jobb pitvarba terjedo mellékveserák sikeres mutéti eltávolítása.

The authors discuss a case of a 47-year old female, who underwent a left adrenalectomy for adrenocortical carcinoma. A few months later the tumour locally recurred and spread through the inferior vena cava into the right atrium. The tumour thrombus almost completely occluded the lumen of the inferior vena cava resulting in significant hepatic congestion, ascites and oedema of the lower extremities. The whole tumour thrombus was successfully removed through the right atrium under visual control using extracorporeal circulation in deep hypothermic (20 degrees C) circulatory arrest. The locally recurred tumour from the site of the left adrenal gland was also removed a month later. The histological examination revealed moderately differentiated adrenocortical carcinoma with a proliferation rate higher than 10%. Thereafter, patient underwent adjuvant oncological therapy and she has been disease free in the last one year. Clinical data suggest that tumour thrombus of various origin that grow into the inferior vena cava can be safely removed using extracorporeal circulation (with or without cardiac arrest), and in such cases, when the primary tumour is resectable, the prognosis is relatively good.

Rapid re-enlargement of a macroprolactinoma after initial shrinkage in a young woman treated with bromocriptine.

We report the case of a macroprolactinoma in a 32-year-old woman, who presented with secondary amenorrhea, galactorrhea, increased plasma prolactin level (3259 ng/ml), headache and bi-temporal visual field defect. Magnetic resonance imaging showed a large pituitary tumor. The patient responded well to bromocriptine (7.5 mg/day) with improvement of clinical symptoms and normalization of plasma prolactin within a few weeks. After 4 months of treatment, tumor size was also reduced markedly. During continued treatment at the same dose of bromocriptine the plasma prolactin level remained normal, but after 8 months of treatment the patient suddenly complained of worsening of her visual fields, and magnetic resonance imaging indicated re-enlargement of the tumor. Bromocriptine was discontinued and transsphenoidal pituitary surgery was performed. After surgery the visual field defect improved, but postoperative plasma prolactin level (1104 ng/ml) and magnetic resonance imaging indicated a residual tumor. Postoperative treatment with quinagolide (0.15 mg/day) resulted in disappearance of all clinical symptoms, normalization of prolactin level and a reduction in size of the residual tumor. This case demonstrates that a dissociation of the inhibitory effect of bromocriptine on tumor size and prolactin level may rarely develop during the course of drug treatment in a patient with macroprolactinoma.