Although epinephrine is known to induce HO activity, steroids are the only nonmetalloporphyrin compounds known to inhibit the induction of HO-1. The effect of different medications on HO activity has not been systematically investigated. Furthermore, the treatment of diabetes by modifying the levels of glucose and the production of AGEs may modulate the level of oxidative stress and indirectly change HO-1 activity and CO produc-tion. Therefore, the effect of treatment on CO levels should also be investigated in future studies.
Oxidative stress's tag archives
Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood: Conclusion
Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood: Discussion
Competitive inhibitors of HO such as Sn-meso-porphyrin and zinc protoporphyrin effectively reduce hyperbilirubinemia and CO production in newborns, but their effects have not been evaluated in adults. HO activators in asthmatic patients have been investigated in a previous study where the inhalation of hemin was shown to increase the levels of exhaled CO, whereas such levels were reduced in steroid-treated patients. Furthermore, in the same study we showed that the high levels of exhaled CO found in asthmatic patients were associated with an increased expression of HO-1. Taken together, these data indicate that the exhaled CO concentration may reflect HO activity. Source
Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood: Exhaled CO Concentration During OGTT
Exhaled CO Concentration During OGTT Maximal increase in glucose concentration (from 3.9 ± 0.2 to 5.5 ± 0.1 mmol/L, at 15 min; p < 0.05) was associated with a significant increase in the level of exhaled CO (from 3.0 ± 0.5 to 6.3 ± 1.0 ppm; p < 0.05). Both parameters returned to the baseline 40 min after glucose administration (Fig 2). Discussion Exhaled CO levels are elevated in patients with diabetes, correlate with blood glucose levels and duration of the disease, and may reflect the amount of HO-1 induction caused by increased oxidative stress.
Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood: OGTT
Blood Glucose Level Measurement Blood glucose levels were measured with a portable blood glucose meter (Reflolux S; Boehringer Mannheim; Mannheim, Germany), which was previously shown to provide glucose levels comparable to those of the hexokinase method and to have a low coefficient of variation. The device was calibrated before every series of measurements. OGTT An OGTT was performed in the morning in five fasting healthy volunteers, with the administration of75 g glucose. Monitoring of glucose levels was performed every 10 min for 2 h after glucose administration. The concentration of exhaled CO was monitored at the same time points. The OGTT response was normal (exhaled CO, < 200 mg [11.1 mmol] over 2 h) in all subjects evaluated.
Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood: Materials and Methods
Subjects We have compared exhaled CO levels in 8 patients with type 1 disease (4 men, 4 women; [mean ± SEM] age, 50 ± 8 years), in 16 patients with type 2 disease (5 men, 11 women; age, 63 ± 8 years), and in 37 healthy subjects (20 men, 17 women; age, 33 ± 3 years). All subjects were lifelong nonsmokers. The mean duration of disease for patients with type 1 diabetes was 20 ± 5 years and, for type 2 patients,11 ± 2 years.
Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood
A New Test for Monitoring the Disease? In diabetes, the interaction of glycated proteins with their cell-surface binding sites leads to oxidative stress, manifested by the appearance of mal-ondialdehyde determinants in the vessel wall, thio-barbituric acid-reactive substances in the tissues, and induction of the transcription factor nuclear fac-tor-KB and of heme oxygenase (HO)-1. This may explain the previously reported finding of elevated exhaled carbon monoxide (CO) levels. Oxidative stress also plays an important role in the development of diabetes-related complications; superoxide anions and elevated levels of plasma peroxide have been implicated in retinal damage, and lipid peroxides in the severity of coronary atherosclerosis in patients with type 1 and type 2 diabetes.
CFs are also observed in other chronic inflammatory diseases, in which an increased incidence of cancer is also documented . In agreement with the link to inflammation, CF values were positively correlated with necroinflammatory scores. ACS was reduced to near normal values not only in responders, but also in nonresponders and relapsed patients. In the 15 patients whose control biopsies were available, inflammatory grading was reduced from 4.0±1.5 to 2.8±1.9. Given that in general inflammation precedes fibrogenesis, IFN treatment should be the most efficient, if given early in the disease process. Reduction of chronic oxyradical-related DNA damage might also reduce the risk of hepatocarcinoma.
The third biomarker of oxidative stress, clastogenic activity in patient’s plasma, represents a global assay for increased superoxide production in the organism. A positive CF-test indicates an increase in circulating endogenous clastogens formed via superoxide-mediated pathways. Among the lipid peroxidation products, the aldehyde 4-hydroxynonenal is clastogenic at 0.1 pM concentration. MDA, on the other hand, is only a weak clastogen. This explains why no positive correlation was found between ACS and MDA.
However, the global decrease of oxyrad-ical formation and consequently of nonenzymatic oxidation of lipids can explain the observed reduction in MDA equivalents. It is interesting that MDA was positively correlated with fibrosis scores and the serological marker of fibrogenesis, PIIIP. Other authors have reported that MDA is associated with activation of stellate cells and with the stimulation of collagen alpha 1 gene expression. As previously reported, IFN prevents further development of fibrosis and improves the serological markers of fibrogenesis . In the NR and RR patients, fibrosis score and PIIIP values remained constant after treatment in the majority of the patients. However, in two of the three responders with control biopsies, the fibrosis score was reduced from two to one with concomitant normalization of PIIIP.
The results of the present study confirm that patients with chronic hepatitis C are in oxidative stress (ie, their prooxidant-antioxidant balance has shifted towards the prooxidant side). When the antioxidant defences are overwhelmed because of increased free radical production, oxidative damage occurs in lipids, proteins and nucleic acids. Among the three biomarkers of oxidative stress chosen for this study, the quantification of lipid peroxides by the measurement of thiobarbituric acid reactive materials is a convenient and frequently used assay.
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