Long Term Oral Contraceptive Administration is Associated with Low Serum Levels of Nitric Oxide, Vitamin C and Vitamin E

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Vincenzo Sepe ◽  
Marilena Gregorini ◽  
Teresa Rampino ◽  
Pasquale Esposito ◽  
Rosanna Coppo ◽  
...  

Abstract Background Inflammaging is a persistent, low−grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation. Methods We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low−flux bicarbonate hemodialysis, 2) Low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period. Results Hemodialysis kynurenine and kynurenine/L − tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers period, L − tryptophan serum levels remained unchanged vs both low−flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L − tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low−flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line. Conclusions The treatment with more biocompatible hemodialysis procedure as low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low−flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level. Trial registration NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Mehdi Nematbakhsh ◽  
Zahra Pezeshki ◽  
Fatemeh Eshraghi-Jazi ◽  
Farzaneh Ashrafi ◽  
Hamid Nasri ◽  
...  

Background. The nephroprotective effect of vitamins E and C or losartan against cisplatin (CP)- induced nephrotoxicity when they are accompanied by estrogen was investigated.Methods. The ovariectomized rats received estradiol valerate for two weeks. At the end of the first week, a single dose of CP (7 mg/kg, IP) was also administered, and they received placebo (group 1), vitamin E (group 2), vitamin C (group 3), or losartan (group 4) every day during the second week, and they were compared with another three control groups.Results. CP alone increased the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and kidney tissue damage score (KTDS), significantly (P<0.05), however at the presence of estradiol and CP, vitamin C, vitamin E, or losartan not only did not decrease these parameters, but also increased them significantly (P<0.05). The serum level of superoxidase dismutase (SOD) was reduced by CP (P<0.05), but it was increased when estradiol or estradiol plus vitamin C or losartan were added (P<0.05).Conclusion. The particular pharmacological dose of estrogen used in this study abolish the nephroprotective effects vitamins C and E or losartan against CP-induced nephrotoxicity.


2004 ◽  
Vol 23 (8) ◽  
pp. 391-398 ◽  
Author(s):  
M Koyuturk ◽  
S Bolkent ◽  
S Ozdil ◽  
S Arbak ◽  
R Yanardag

In this study, the effect of a combination of vitamin C, vitamin E and selenium on ethanol-induced duodenal mucosal damage in rats was investigated morphologi-cally and biochemically. The duodenal mucosal injury was produced by oral administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg) and selenium (0.5 mg/kg) for 3 days and absolute ethanol 1 hour after last antioxidant administration and were sacrificed 1 hour after absolute ethanol. Extreme degeneration in intestinal mucosa of rats given ethanol was observed morphologically. In addition, an increase in neuronal nitric oxide synthase immunoreactive areas was observed in the rats of the group given ethanol. On the other hand, a normal morphological appearance and a decrease in neuronal nitric oxide synthase immunoreactive areas were detected in the rats given ethanol+vitamin C+vitamin E+selenium. In the group to which ethanol was administered, an increase in serum cholesterol and a decrease in serum albumin levels were determined. On the other hand, in the group to which ethanol+vitamin C+vitamin E+selenium were administered, serum cholesterol value decreased, and the serum albumin level increased. As a result, we can say that the combination of vitamin C, vitamin E and selenium has a protective effect on ethanolinduced duodenal mucosal injury.


VASA ◽  
2004 ◽  
Vol 33 (1) ◽  
pp. 3-11 ◽  
Author(s):  
van der Loo ◽  
Koppensteiner ◽  
Lüscher

Altern ist ein wichtiger kardialer und vaskulärer Risikofaktor. Für das Gefäßaltern sind genetische, mechanische und hämodynamische Faktoren ausschlaggebend. So sind altersabhängige Veränderungen in Gefäßen, welche weniger Pulsatilität und Blutdruck ausgesetzt sind, wie Kapillaren und Venen, geringer oder abwesend. Vor allem in den großen Widerstandsgefäßen kommt es im Laufe des Alterns morphologisch zu einer Intima- und Mediaverdickung, verknüpft mit einer vermehrten Einlagerung von Matrixsubstanzen, und letztlich resultierend in verminderter Compliance der Gefäße. Es lassen sich Funktionsstörungen des Endothels nachweisen. Hier kommt es zu einer deutlichen Heraufregulierung der endothelialen Nitric Oxide Synthase (eNOS), welche für die Produktion des endogenen Vasodilatators Nitric Oxide (NO) verantwortlich ist. Paradoxerweise sind trotzdem die Vasorelaxationen im Alter vermindert, da es gleichzeitig zu einer erhöhten Produktion freier Radikale, im Besonderen Superoxid (O2-) kommt. O2- und NO bilden in einer schnell ablaufenden chemischen Reaktion Peroxinitrit (ONOO-), welches Proteine nitriert. Durch diese Nitrierung kommt es zur funktionellen Beeinträchtigung dieser Proteine, so dass verschiedene Signalübertragungswege, z.B. Tyrosilierung von Enzymen, blockiert werden. Primärer Ort der Bildung freier Sauerstoffradikale sind die endothelialen Mitochondrien. Bislang ungeklärt ist, ob der oxidative Stress als ein zentrales Ereignis des Gefäßalterns pharmakologisch beeinflussbar ist. Hier standen vor allem antioxidativ wirkende Vitamine im Mittelpunkt des Interesses. Überraschenderweise wird jedoch Vitamin E im Tiermodell vermehrt mit steigendem Alter in der aortalen Wand eingelagert, was im Rahmen eines altersassoziierten gegenregulatorischen Mechanismus zur Abwendung des vermehrten oxidativen Stresses erfolgt. Umgekehrt ist Vitamin C signifikant vermindert. Es bleibt abzuwarten, ob das Gefäßaltern durch Vitamin C oder andere Antioxidantien günstig beeinflusst werden kann. Für Statine und ACE-Hemmer wurden schon Wirkungen beschrieben, die mit Schlüsselmechanismen des Gefäßalterungsprozesses interferieren. Die Entwicklung therapeutischer Interventionen zur Verlangsamung des Gefäßalterns wird für das Auftreten von Herz- und Gefäßerkrankungen im Alter in Zukunft große Bedeutung haben.


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