Vasilios Ragos

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.

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.

Cytotoxic effect, antitumour activity and toxicity of organotin derivatives with ortho- or para-hydroxy-benzoic acids

The cytotoxic and antitumour activities of five organotin complexes (1–5) with o-hydroxy-benzoic or p-hydroxy-benzoic acids were evaluated in a series of in vitro and in vivo experiments. All complexes exhibited strong cytotoxic activity against all cancer cells lines, whereas complexes 1, 2 and 4 induced apoptosis at significantly lower doses than complexes 3 and 5. Human cancer cells treated with increasing concentrations of complexes 1, 2 and 4 gradually lost their ability to form colonies. Only complexes 1 and 2 inhibited colony formation efficiency in rat leiomyosarcoma cells. Histopathology of liver and kidney showed mild damage and lung oedema after a single injection of 10 mg/kg body wt of complex 1 to Wistar rats. At higher doses (100 mg/kg body wt) brain stem oedema was observed. Daily administration of tumour-bearing Wistar rats (leiomyosarcoma) with 1 mg/kg body wt of complex 1 until death reduced the mean tumour growth rate by more than 3× fold and prolonged mean survival time by 120%. These findings indicate that the organotin complexes with ortho- or para-hydroxy-benzoic acids possess potent cytotoxic and antitumour activity and they could be used as potential chemotherapeutic agents.

OXIDATIVE STRESS INCIDENCE ON THE SEVERITY OF KNEE OSTEOARTHRITIS

The aim of the study was to examine the incidence of oxidative stress on the severity of knee osteoarthritis (OA). Data were obtained from a previous pilot controlled trial among patients, diagnosed with OA in one or both knees, that were randomly assigned into two different treatment groups and were either supplemented with ascorbic acid and Vitamin E daily per os or treated with meloxicam. The following markers were estimated: A. Clinical markers: functionality of the knee (WOMAC index), pain (using a pain visual analogue scale) and severity of OA (Kellgren–Lawrence grading scale) B. Laboratory markers: total antioxidant capacity (TAC) and malonyldialdehyde (MDA) levels in the synovial fluid. The TAC of the knees was moderately correlated with the severity of OA and the level of pain whilst MDA concentration was weekly correlated. An average change of 5mM of a-tocopherol in TAC (4.6–5.5mM of a-tocopherol) defines the shift among stages of OA and the level of pain experienced by the patients. Neither TAC...

Modulation of cisplatin cytotoxic activity against leiomyosarcoma cells by epigallocatechin-3-gallate

Abstract The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC50 of cisplatin (8.6 μΜ) as a reference value and a concentration of EGCG (30 μΜ) that caused a non-significant reduction in cell proliferation. Pre-treatment of cells with EGCG for 24 h before the addition of cisplatin increased cytotoxicity up to 8.5% (p < 0.05) and the number of apoptotic cells by 40%. Epigallocatechin-3-gallate failed to alter S-phase cell cycle arrest induced by cisplatin and to modulate cisplatin effects on mitochondrial function. These results indicate that pre-treatment with EGCG could be used as an adjunctive therapy to maximise effectiveness of chemotherapy.

Functional responses of human and rabbit platelets induced by milk from indigenous Greek dairy goats (Capra Prisca)

The aim of this study was to investigate the biological properties of goat milk from the indigenous Greek breed (Capra Prisca). The activity of the milk on platelet aggregation and thromboxane B2 production was evaluated on platelets isolated from blood obtained from both humans and rabbits. To further understand the biological properties of the milk ascorbic acid, linoleic and linolenic acid, were also tested. Ex vivo trials showed that milk from indigenous. Greek dairy goats (Capra Prisca) inhibited platelet aggregation at a dose dependent manner, both in humans and rabbits and decreased production of TXB2. The milk’s ability to inhibit platelet aggregation and reduce TXB2 production could be attributed to its high content in antioxidant substances and poly-unsaturated fatty acids (such as ascorbic acid and linolenic acid), when originating from grazing goats in semi-mountainous shrublands. The paper provides information for nutritionists and health professionals, about the biological properties of specific types of milk and their potential use as functional foods.