Spyridon Karkabounas

Antioxidant protection during the menstrual cycle: the effects of estradiol on ascorbic–dehydroascorbic acid plasma levels and total antioxidant plasma status in eumenorrhoic women during the menstrual cycle

Background. Estrogens, apart from their classic role as steroid hormones, also possess significant antioxidant properties. The present study was undertaken to assess the antioxidant potential of the female during the various menstrual phases and to investigate the correlation between ascorbic acid, dehydroascorbic acid plasma levels, total antioxidant plasma status, and estradiol levels. Design and methods. Thirteen eumenorrhoic women were studied. Ascorbic acid and dehydroascorbic acid plasma levels, total antioxidant plasma status, estradiol, progesterone, luteinizing hormone, and follicle‐stimulating hormone during time of menstruation, midfollicular phase, time of ovulation, and midluteal phase were determined. Ascorbic–dehydroascorbic acid ratio was also calculated. Results. A progressive significant rise in ascorbic acid plasma levels (p<0.01), ascorbic–dehydroascorbic acid ratio (p<0.001), and total antioxidant plasma status (p<0.05) from menstruation to ovulation was observed. Moreover, a significant decrease in dehydroascorbic acid was found at the same phases (p<0.05). Changes of estradiol levels during the menstrual cycle correlated positively with the changes of ascorbic acid levels and total antioxidant plasma status (p<0.05). Furthermore, estradiol levels correlated positively with ascorbic acid levels (p<0.05, r<0.5), ascorbic–dehydroascorbic acid ratio (p<0.05, r<0.5), and total antioxidant plasma status (p<0.05, r<0.8) in all menstrual phases. Conclusions. An elevated antioxidant protection during ovulation and the midluteal phase appears to be present in eumenorrhoic women. Moreover we observed a cyclic variation in the antioxidant parameters we assayed in the females in the present study, which could be due to cyclic changes in estradiol levels.

Anticancer and cytotoxic effects of a triorganotin compound with 2-mercapto-nicotinic acid in malignant cell lines and tumor bearing Wistar rats.

Nowadays, investigation for possible therapeutic applications of various metal-based drugs attracts the scientific interest worldwide. The triorganotin compound bis[triphenyltin(IV)](3-carboxy-pyridine-2-thionato) (SnMNA), was tested for its anti-proliferative and antitumor activities. Cytotoxic activity was assessed by Trypan blue and 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide assay (MTT). SnMNA exhibited potent cytotoxic effects against leiomyosarcoma cells (LMS) and human breast adenocarcinoma cells (MCF-7), which is 200 times stronger than that of cisplatin. Moreover, SnMNA induced significant apoptosis in LMS and MCF-7 cells characterized by flow cytometry analysis and DNA fragmentation. Acute and chronic toxicity studies on Wistar rats caused kidney and lung toxicity at a single dose of 80mg/kgBody Weight (BW) or four repeated doses of 8mg/kgBW once per week. Furthermore, antitumor activity studies on sarcoma bearing Wistar rats revealed that SnMNA complex at four repeated doses of 5.4mg/kgBW every three days prolonged mean survival time of the animal at 200% and decreased mean tumor growth rate (MTGR) compared to the control group (p<0.05). It is noteworthy to mention that the 30% (3 out of 10) of the bearing animals were totally cured. These findings indicate that SnMNA might be a promising new antitumor agent.

Oxidative stress in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and the significant role of vitamin C and E supplementation

PurposeChronic renal failure patients undergoing peritoneal dialysis (PD) are characterized by increased oxidative stress (OS), which is associated with enhanced cardiovascular risk. Moreover, oxidative stress also contributes to peritoneal membrane changes and ultrafiltration failure. The aim of this study was to evaluate OS in PD patients and the effect of treatment with ascorbic acid and α-tocopherol.MethodsPlasma, erythrocyte, urine, and peritoneal effluent samples from 20 patients on PD were evaluated for glutathione peroxidase and superoxide dismutase activity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as protein carbonyl formation, before and after administration of vitamin C, alone or in combination with vitamin E, in comparison with 10 apparently healthy control individuals.ResultsAll studied markers showed enhanced OS in the PD group, compared to controls. The supplementation of vitamin C and E resulted in improvements of all the OS markers, as indicated by increased erythrocyte antioxidant enzymes activity and TAC levels, as well as decreased MDA concentration and carbonyl compound formation.ConclusionsThe oral supplementation of antioxidant vitamins C and E, in combination, can lead to decreased OS, thus providing a useful and cost-effective therapeutic option in PD patients.

Changes in copper and zinc plasma concentrations during the normal menstrual cycle in women

Objective. To investigate whether there is a fluctuation of the copper and zinc plasma levels during the menstrual cycle and if this correlates to the physiological fluctuations of estradiol and progesterone plasma concentrations in eumenorrhoic women. Methods. We studied 14 eumenorrhoic women. Copper (Cu), zinc (Zn), estradiol (E2) and progesterone (Prg) plasma concentrations, during time of menstruation (time 1), midfollicular phase (time 2), time of ovulation (time 3) and midluteal phase (time 4) were determined. Results. We observed significant changes in both copper plasma concentrations and zinc plasma concentrations during the four times studied (p < 0.05). The changes of Cu during the various phases correlated negatively with the changes in E2 (r > 0.5, p < 0.05), whereas the changes of Zn correlated positively with those of E2 (r > 0.8, p < 0.05). We were unable to demonstrate any statistically significant correlation between Cu and Prg or Zn and Prg. Conclusions. This study indicates that there is a cyclic fluctuation of Cu and Zn concentrations in plasma during the menstrual cycle, in healthy eumenorrhoic women. This cyclic fluctuation might be due to the cyclic fluctuation of plasma levels of E2.

Milk of Greek sheep and goat breeds; characterization by means of proteomics.

UNLABELLED Over the past 30years there has been a growing interest to unravel the dynamic framework of the milk proteome, and now that available technology is mature enough to enable techniques of protein fractionation and identification, this process is on-going. Due to its rarity and unique biological traits, as well as its growing financial value, milk of dairy Greek animals is continuously attracting interest from both the scientific community and industry. In the present study we employed cutting-edge proteomics methodologies to investigate and characterize, in depth, the proteome of whey from all pure-breed Greek sheep and goats. A mean of >500 protein groups were identified in whey from each breed of each animal species, reporting for the first time the proteome dataset of this precious biological material. Given its high nutritional value, the protein properties exposed herein will govern future steps in optimizing characteristics and features of sheep and goat milk products. SIGNIFICANCE In the present study we employed cutting-edge proteomics methodologies to investigate and characterize, in depth, the proteome of milk from all pure-breed Greek sheep and goats. A mean of >500 protein groups were identified in milk whey from each breed of each animal species, reporting for the first time the proteome dataset of this precious biological material. Given its high nutritional value, the protein properties exposed herein will govern future steps in optimizing characteristics and features of sheep and goat milk products.

Effects of catechin and epicatechin on superoxide dismutase and glutathione peroxidase activity, in vivo

Abstract Objectives The objective of this study was to investigate the effects of catechin and epicatechin on the activity of the endogenous antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) (as well as the total antioxidant capacity (TAC)) of rats after intra-peritoneal (i.p.) administration. Methods Twenty-four Wistar rats were randomly divided into two groups: the experimental group which was administered daily with a 1:1 mixture of epicatechin and catechin at a concentration of 23 mg/kg body weight for 10 days and the control group which was injected daily with an equal amount of saline. Blood and urine samples were collected before and after the administration period, as well as 10 days after (follow-up). Results Intra-peritoneal administration of catechins led to a potent decrease in GPx levels and a significant increase in SOD levels. TAC was significantly increased in plasma and urine. Malonaldehyde levels in urine remained stable. In the animals treated with catechins, SOD activity showed a moderate negative correlation with GPx activity. Discussion Boosting the activity of the antioxidant enzymes could be a potential adjuvant approach for the treatment of the oxidative stress-related diseases.

Low selenium levels in serum and increased concentration in neoplastic tissues in patients with colorectal cancer: Correlation with serum carcinoembryonic antigen

There is growing evidence to show that administration of selenium (Se) is associated with a substantial reduction in the incidence and mortality of various cancer types such as skin, prostate, lung, and colorectal cancer (CRC) as well as in sarcomas in both animals and humans [1,2]. Epidemiological studies have shown a reduced risk for the same neoplasms for people living in geographic areas with comparatively high soil Se levels. Similarly, epidemiological and experimental studies suggest an inverse relationship between intake of dietary Se and/or a low-fat intake and CRC risk [3]. CRC is one of the leading causes of cancer-related deaths. Approximately 95% of cases are sporadic. Early detection and prevention are the two most important considerations facing CRC. Low Se intake and plasma levels have been implicated in the multistep process of colorectal carcinogenesis. However, their relationship remains elusive and intriguing [3 /5]. There are studies suggesting that selenium supplementation decreases the cyclooxygenase-2 (COX-2) protein and PGE-2 levels in cancer cells and increases the efficacy of cetuximab in patients with advanced CRC [6 /8]. Material and methods

Inhibition of benzo(a)pyrene-induced carcinogenesis by vitamin C alone and by vitamin C/vitamin E and selenium/glutathione

The reduction on peroxidation caused by benzopyrenes by some naturally occurring antineoplastic agents was studied in this experimental work. Inhibition/reduction of experimental carcinogenesis induced by benzo(a)pyrene by vitamin C alone and by vitamin C/vitamin E and selenium/glutathione was attempted in 224 female Wistar rats divided in four groups. Injected with 10.08 mL benzo(a)pyrene, the animals were treated with some naturally occurring substances like vitamin C alone and a combination of anticarcinogens. By calculating the carcinogenic potency of benzo(a)pyrene and the anticarcinogenic potency of substances used as well as histological examination of developed tumors and survival time of treated animals, it was found that vitamin C exerts a significant anticarcinogenic effect of 8.3 units and that the combination of the two anticarcinogens used produced a significant prolongation of the animals survival time with anticarcinogenic potency of 22.1 and 22.2 units, respectively. This is considered a potent anticarcinogenic effect. The question of an additional supportive administration of such agents complementary to the conventional cancer chemotherapy in humans is raised. Of course, further studies are needed.

Cytotoxic and anticancer effects of the triorganotin compound [(C6H5)3Sn(cmbzt)]: An in vitro, ex vivo and in vivo study

Since the initial success of cisplatin, metal complexes and organometallic compounds have been gaining growing interest in cancer therapy. It is well known that organotin(IV) compounds display strong biological activity. The triorganotin compound [(C(6)H(5))(3)Sn(cmbzt)] (cmbzt=5-chloro-2-mercaptobenzothiazole) (SnCMB), was tested for its antiproliferative and antitumour activities. Two sets of experimental procedures were followed: (1) In vitro and ex vivo procedures included the study of the cytotoxic activity of the complex against leiomyosarcoma cells (LMS) and on a normal human fibroblast line (MRC5) by the MTT assay (cell proliferation), colony formation efficiency and flow cytometric analysis with Annexin V-FITC. The anticoagulation properties of the complex were also studied. (2) In vivo procedures included acute toxicity studies and finally administration of the complex to tumour bearing Wistar rats. The results showed that the complex exhibited potent cytotoxic activity (LMS IC(50)=155 nM) and induced significant apoptosis against LMS cells. Acute toxicity studies on Wistar rats presented kidney and liver toxicity at a single dose of 40 mg/kg body wt. Furthermore, antitumour activity studies on sarcoma bearing Wistar rats revealed that SnCMB complex, administrated in two different therapeutic schemes (treated with 4 × 2 mg/kg body wt every 5 days and 3 × 2.67 mg/kg body wt every 10 days of SnCMB complex), prolonged mean survival time (by 50% and 70% respectively), but failed to decrease the mean tumour growth rate (MTGR) compared to the control group (p<0.01). In conclusion, the organic complex SnCMB possess potent cytotoxic and antimetastatic effects, and low toxicity introducing it as possible successor of organometallic compounds used nowadays in chemotherapy.

Correlation of bioelectrical impedance analysis phase angle with changes in oxidative stress on end-stage renal disease patients, before, during, and after dialysis

Abstract Chronic kidney disease is a condition that promotes oxidative stress. There are conflicting evidence about the role of hemodialysis on oxidative stress, that are mostly related with the various types of membrane materials used, the quality and type of dialysate, the method used, etc. The phase angle (PhA), which is determined with bioelectrical impedance analysis (BIA), measures the functionality of cell membranes. In this study, the correlation of the PhA with parameters of oxidative stress is attempted for the first time. We evaluated parameters of oxidative status as total antioxidant capacity (TAC) in erythrocytes (RBCs) and plasma of patients with ESRD undergoing hemodialysis with low flux synthetic polysulfone membranes. Measurements were recorded from 30 patients (16 men and 14 women) aged 64 ± 14 years before, during, and after dialysis, and in 15 healthy volunteers aged 56 ± 12 years The PhA was obtained by BIA. The plasma TAC increased significantly (41%, p < 0.05). Intracellular TAC noted a non-significant increase. Total antioxidant capacity of the patients before and after hemodialysis was significantly lower from the healthy volunteers (p < 0.05) showing that ESRD patients are at the state of increased oxidative stress. The PhA increased in significantly positive correlation with plasma TAC at the end of hemodialysis. The process of hemodialysis with biocompatible synthetic membranes and bicarbonate dialysate improved plasma TAC. The positive correlation of PhA with extracellular TAC could evolve to a method of oxidative stress estimation by BIA but further research is needed.