The effects of acute melatonin and ethanol treatment on antioxidant enzyme activities in rat testes

The pineal hormone melatonin (N-acetyl, 5-methoxytryptamine) was recently accepted to act as an antioxidant under both in vivo and in vitro conditions. In this study, we examined the possible preventive effect of melatonin on ethanol-induced lipid peroxidation in rat testes. Thirty-seven male Wistar albino rats, 5.5-6 months old, were randomly divided into four groups (9-10 animals in each). The first group (control animals) received 4% ethanol at similar intervals to the experimental groups to equalize the stress effect. The second group received only melatonin i.p. 7 mg kg(-1) bw three times over 1.5 h intervals. The third group received only 30% alcohol 3 g kg(-1) bw twice daily. The fourth group were treated with melatonin and ethanol according to the above protocole, melatonin injections preceeding ethanol treatments. The product of lipid peroxidation, malondialdehyde (MDA) and antioxidant enzymes, superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured in the post-mitochondrial fraction of the testes. MDA levels were significantly increased due to acute ethanol intoxication. GPx activity was higher in the three experimental groups than the control levels. The activity of CAT was increased significantly in the melatonin plus ethanol-treated group but the other groups appeared not to be influenced by acute ethanol treatment. Cu-Zn SOD activity remained unaltered. These results suggest that antioxidants may be a protective agent for the testicular injury caused by ethanol consumption. (C) 2001 Academic Press

Coadministration of melatonin and estradiol in rats: Effects on oxidant status

This study was designed to investigate the effects of melatonin and estradiol (E2) on lipid peroxidation and antioxidant defense enzymes in blood and liver tissue when administered in vivo. Wistar albino rats were divided into three experimental groups and treated with either estradiol (25 mg/kg bw, s.c.), melatonin (i. p.), or melatonin plus E2, whereas control animals had diluent injections only. Melatonin was given 10 mg/kg bw x 2 intraperitoneally 30 min before and 60 min after E2 treatment to the melatonin plus E2 group. Animals were sacrificed three hours after the estradiol injection, and their blood and liver tissues were prepared for biochemical analyses. Tissue malondialdehyde (MDA) levels and antioxidant enzyme activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) - were determined in the postmitochondrial fraction, and the results were compared. Estradiol injection caused significant increases in both MDA levels and GPx activity in liver. When melatonin was administered in combination with E2, the effect of estradiol on MDA levels was abolished. A significant decrement in SOD activity occurred in melatonin-treated animals. GPx activity in the blood of E2 plus melatonin-injected animals was significantly higher than those in control animals. Melatonin-treated animals exhibited relatively lower levels of SOD activity than those from the control and E2 plus melatonin groups. This indicates that estradiol could exert oxidant action resulting in an increment in tissue malondialdehyde levels. Enhanced activity of GPx in both liver and blood following melatonin injection may indicate the contribution of this neurohormone on the antioxidant defense

The association between preeclampsia and angiotensin-converting enzyme insertion/deletion polymorphism

Background: Plasma and tissue angiotensin-converting enzyme (ACE) activities are believed to be under genetic control. Increased ACE activity due to the deletion polymorphism of the ACE gene is associated with a wide variety of diseases that exhibit endothelial disturbances. Available reports suggest that the incidence of ACE gene deletion polymorphism associated with preeclampsia varies depending on the study population and geographic location. In this study, we examined the insertion/ deletion genotype distribution and the activity of ACE in preeclamptic pregnants. Methods: Ninety-five preeclamptic and 50 normotensive pregnant patients, both in their third trimester, as well as 39 healthy nonpregnant individuals were included in the study. Gene polymorphism was studied by the polymerase chain reaction followed by the agarose electrophoresis. Pearson's chi(2) test was used for the statistical evaluation of the allele frequency, and Student's t-test for the ACE activity. Results: The presence of D allele was found to be associated with preeclampsia (p < 0.05, odds ratio = 1.53; df = 1; 95% Cl = 1.007-2.338). The linfluence of allelic distribution on the enzyme activity was observed in the preeclamptics bearing II genotype, who exhibited significantly lower activity of ACE than that of the patients with the other genotypes (p<0.05). Conclusion: We found an association between the genotype II and low ACE activity in preeclamptic women and an association between D allele frequency and preeclampsia. Pregnancy alone did not have an effect on the ACE activity. (C) 2004 Elsevier B.V. All rights reserved

Evaluation of the effect of low-dose oral theophylline therapy on some bone turnover markers and serum prolidase I activity in mild asthmatics

Hypercalcemia and hypercalciuria observed both in humans and in animals who were on long-term theophylline therapy, prompted us to investigate whether oral theophylline treatment at optimal doses causes any adverse side effects on bone metabolism in mild asthmatics. Therefore, serum osteocalcin (BGP) and total alkaline phosphatase (TALP, EC 3.1.3.1) as bone formation markers, serum prolidase I(EC 3.4.13.9) activity as a marker for collagen metabolism, urinary deoxypyridinoline (Dpd), hydroxyproline (Hyp) and fasting urinary calcium as bone resorption markers, were measured in 18 mild asthmatics who had been treated with theophylline over 1-10 years. Among measured bone turnover markers, BGP, TALP, and Hyp levels were found to be increased in mild asthmatics; and BGP showed the greatest percent mean increase (98%) over the healthy subjects. However, these increments did not exceed the upper reference limits. Serum prolidase I activity was also increased in mild asthmatics receiving theophylline. Our results indicate that theophylline therapy at optimal doses may not exert adverse side effects on bone homeostasis, but patients receiving supratherapeutic doses of theophylline should be under close examination in order to predict future bone mass status. (C) 1999 Academic Press

Platelet and Other Hemostatic Characteristics in Patients With Chronic Urticaria

Several publications have pointed out the importance of coagulation and fibrinolysis in the occurrence of chronic urticaria (CU), but only a few indicated the direct role of platelets. We assessed platelet aggregation and evaluated parameters of coagulation and fibrinolysis in patients with CU. Patients (n = 34) diagnosed as having CU and 36 healthy controls were enrolled. Platelet aggregation was assayed using an impedance aggregometer and adenosine diphosphate, arachidonic acid, thrombin receptor-activating peptide (TRAP), and ristocetin as agonists. In patients with CU, significantly decreased platelet aggregation to some agonists (ristocetin and TRAP) was observed. The D-dimer levels were elevated, mean platelet volume was decreased, but no alteration was observed in other coagulation assays. Elevated D-dimer levels indicated that coagulation and fibrinolysis are activated in the patients with CU. Evaluation of platelet function may contribute to identify the role of these cells in the pathogenesis of CU

Urine 8-isoprostane F-2 alpha concentrations in patients with neurogenic bladder due to spinal cord injury

Background: Isoprostanes are prostaglandin-like end products of arachidonic acid peroxidation that are produced by a free radical-catalyzed mechanism. Considering its free radical-dependent formation and potent contractor effect, it is postulated that isoprostane 8-iso PGF(2alpha) may play an important role in oxidative stress-related smooth muscle dysfunction. These substances may also influence bladder activity directly by effects on the smooth muscle. The present study was designed to measure traditional biochemical parameters (MDA, TAS, vitamin E) in plasma and 8-iso PGF(2alpha) concentrations in urine of patients with spinal cord injury and to evaluate the relation of urinary isoprostane concentrations to the bladder function. Methods: All spinal cord patients underwent urodynamic evaluations. The biochemical tests were performed in both hyperreflexic bladder group (n = 23) and areflexic bladder group (n = 10), and the findings were compared to those of the patients with normally functioning bladder (controls, n = 19). Results: Urine 8-iso PGF(2alpha) concentrations were significantly increased in hyperreflexic group (median value 0.89 pg/mg creatinine) compared to both control (0.52 pg/mg creatinine) and areflexic groups (p < 0.001). The lowest concentrations of urinary 8-iso PGF(2alpha) were observed in the areflexic group (0.22 pg/mg creatinine), and these were positively correlated to the plasma MDA concentrations in areflexic patients (p = 0.05; r = 0.684). Conclusion: Isoprostanes may be involved in the pathogenesis of neurogenic bladder dysfunction. It may be of value to determine the urinary concentrations of 8-iso PGF(2alpha) in order to distinguish areflexic bladders from the hyperreflectics. (C) 2003 Elsevier B.V. All rights reserved

Association of pre-eclampsia with hyperhomocysteinaemia and methylenetetrahydrofolate reductase gene C677T polymorphism in a Turkish population

Background: Hyperhomocysteinaemia is a common finding in a wide variety of pathological conditions that exhibit endothelial disturbances. In the pathogenesis of pre-eclampsia, endothelial cell activation or dysfunction has been proposed as a central feature, and the presence of hyperhomocysteinaemia in varying degrees has been detected. One of the known causes of hyperhomocysteinaemia is polymorphism in the methylenetetrahydrofolate reductase gene that lowers the activity of the enzyme

Indices of oxidative stress in eutopic and ectopic endometria of women with endometriosis

This study was designed to determine the activities of superoxide dismutase and glutathione peroxidase and some of the lipid peroxidation indices (malondialdehyde and total sulfhydryl groups) in eutopic and ectopic endometria of patients with endometriosis. Ectopic endometrial tissues (ovarian cysts; n=22) were obtained laparoscopically during the preovulatory period. Statistical analyses were made using the Wilcoxon signed-rank test. The levels of malondialdehyde and total sulfhydryl groups were similar in the eutopic and ectopic endometria, whereas the superoxide dismutase activity was found to be significantly higher in the latter (1,893+/-780 vs. 3,512+/-1,502 U/g protein; p=0.002). Although the glutathione peroxidase activity was slightly lower in the ectopic than in the eutopic tissues, the difference was not found to be statistically significant. The malondialdehyde levels were positively correlated with the plasma 17beta- estradiol concentrations in the ectopic endometria (r=0.683, p=0.001). No such correlation was seen in the eutopic tissue. It is suggested that various factors, such as cytokines released by activated macrophages in the peritoneal fluid and 17beta- estradiol itself synthesized by the ovaries, may locally affect the oxidant status of ectopic endometria. Copyright (C) 2004 S. Karger AG, Basel

The effect of COX-2 inhibitor, nimesulide, on angiogenetic factors in primary endometrial carcinoma cell culture

Angiogenesis, the development of new blood vessels from preexisting capillaries, is essential for the development, growth and advancement of solid tumours. Angiogenesis is enhanced by prostaglandins (PGs) that are synthesised by the catalysis of cyclooxygenases (COX-1 and COX-2) from arachidonic acid. COX-2 is upregulated in a variety of malignancies and favours the growth of malignant cells by stimulating proliferation and angiogenesis. The aim of this study is to investigate the angiogenetic process by determining the levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 in endometrial cancer cells and to study the effect of nimesulide, a selective COX-2 inhibitor, on these mediators using cell culture. Endometrial tissue specimens were obtained from subjects with endometrial cancer and intramural leiomyoma. Cells were incubated with either 10 or 50 mu M nimesulide for 24 h. VEGF, MCP-1 and IL-8 concentrations were determined by sandwich quantitative enzyme immunoassay (ELISA). VEGF concentration was significantly higher in cancer cells than normal endometrial cells. VEGF was decreased with 10 mu M nimesulide in cancer cells whereas it remained unaltered in normal cells. Both MCP-1 and IL-8 concentrations were lower in cancer cells than normal cells. MCP-1 levels were decreased with both doses of nimesulide in normal cells, whereas IL-8 levels were significantly affected only by 50 mu M of nimesulide. These results suggest that COX-2 inhibitors may be effective in the treatment of endometrial cancer via suppression of angiogenesis