Chronic heart failure (CHF) due to coronary artery disease (CAD) has been shown to be associated with increased plasma thiobarbituric reactive substances (TBARS) and reduced plasma thiol (PSH) concentrations, suggesting oxidative stress (OS). The aims of the present studies were (a) to determine whether OS is due to CAD or CHF per se and (b) to determine if a wider range of more specific markers of OS are abnormal in CHF. In the first study, two groups of patients (n = 15 each) were compared. Group 1 (11 male, mean age 56 years) had CHF due to CAD and group 2 (12 male, mean age 53 years) had non-CAD CHF. Median plasma TBARS in controls was 7.6 nmol.ml-1, 10.0 nmol.ml-1 in group 1 and 9.3 nmol.ml-1 in group 2 (P < 0.01 both groups vs control). Median PSH was 505 384 and 364 nmol.ml-1 (P < 0.05 and P < 0.01 vs control) respectively. Fifty-three patients with CHF were recruited in the second study. Malondialdehyde and PSH were 10.3 and 409 nmol.ml-1 respectively, compared to control values of 7.9 and 560 nmol.ml-1 (both P < 0.001). The median values for the following additional measures of OS in controls and patients were: erythrocyte superoxide dismutase 131 vs 114 U.l-1 (P = 0.005); caeruloplasmin oxidase 97 vs 197 U.l-1 (P < 0.01); erythrocyte glutathione 1.56 nmol.ml-1 vs 1.77 nmol.ml-1 (P < 0.02); plasma conjugated dienes 0.28 vs 0.33 optical density units (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)
N-nitrosamines are widely spread environmental pollutants of well-known toxicity and carcinogenicity in various animal species. These compounds are metabolically activated by cytochrome P450 system predominantly in the liver and in other tissues into more active metabolites leading to generation of both alkylating agents that alkylate DNA and reactive oxygen species. In the current study, we investigated the influence of four types of N-nitrosamines that are commonly present in the environment [methyethylnitrosamine, (MEN), diethylnitrosamine (DEN), diphenylnitroasamine (DPN) and dimethylnitrosamine (DMN)] on both livers and testes of male rabbits through assessment of 17 β-hydroxysteroid dehydrogenase (17 β-HSD) activity. The protein expression of the three cytochrome P450s (CYP11A1, CYP19A1, and CYP21A2) is involved in the steroidogenesis. The levels of testosterone (T) and estradiol (E2) were also determined in the plasma of N-nitrosamines-treated rabbits after one, four-, eight- and twelve weeks of treatment of male New Zealand rabbits with an oral dose of 0.5 mg/kg B.W/day of each compound. In addition, activities of glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and levels of free radicals measured as thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) level were quantified in both livers and testes. The present study showed that levels of free radicals (TBARS) were markedly increased, whereas GSH levels were depleted in the tissues of both livers and testes after treatment of rabbits with any of N-nitrosamines. In addition, all tested N-nitrosamines inhibited the activities of antioxidant enzyme activities (GR, GST, SOD, and CAT) in hepatic and testicular tissues of rabbits after 12 weeks of treatment. Histopathological examination showed that N-nitrosamines caused lymphocytic infiltration with vascular degeneration and necrosis, congestion of central vein with RBCs hemolysis, dilated sinusoids, as well as fibrosis around portal areas were seen in hepatic tissues. In the testes, histopathological examination displayed disorganized seminiferous tubules with degeneration of germinal epithelium and Sertoli cells. Also, spermatogenic cells had pyknotic nuclei and others were detached from basement membranes of seminiferous tubules, edema was seen between seminiferous tubules. Moreover, the present data showed that MEN and DEN down-regulated the protein expression of both CYP19A1 and 21A2 in both livers and testes of male rabbits. In addition, both MEN and DEN decreased levels of testosterone and estradiol in plasma of treated rabbits. On the one hand, DMN and DPN markedly up-regulated the protein expression of CYP19A1 in both hepatic and testicular tissues of treated rabbits. These compounds potentially increased estradiol and decreased testosterone levels. On the other hand, no correlation was found between the expression of CYP11A1 and levels of both testosterone and estradiol. It is concluded that most of tested N-nitrosamines induce different changes, whic...
Objective-To determine whether unstable angina, which is characterised by recurring episodes of myocardial ischaemia and reperfusion, is associated with oxidative stress (that is, where there is an imbalance between oxidants, such as free radicals, which are in excess and antioxidants).Design-Between group comparison of patients with unstable angina, stable angina, and healthy controls.Setting-The coronary care unit and cardiac investigation ward of a regional cardiology centre.Patients-Twenty five consecutive patients admitted to the coronary care unit with unstable angina. Twenty five consecutive patients admitted to the cardiac investigation ward (patients with stable angina undergoing coronary angiography) were used as controls for the presence of atherosclerosis, drug treatment, and smoking habit. Thirty eight healthy controls (hospital staff and patients admitted for minor surgical procedures who were otherwise healthy) were also studied.Main outcome measures-Thiobarbituric acid related substances (TBARS) (Br Heart J 1992;68:454-7)
1. Neutrophil NADPH oxidase produces the superoxide anion (O2‐) anion radical from oxygen. The thiol containing ACE inhibitor, captopril has been reported to inhibit isolated NADPH oxidase. The above effect of captopril, if present in intact cells, could contribute to the ability of this drug to alleviate neutrophil‐mediated tissue damage. We have, therefore, investigated the effect of captopril on the oxidative activity of intact human isolated neutrophils. 2. The effects of captopril on neutrophil oxidative activity were compared with those of enalaprilat (a non‐thiol ACE inhibitor) and N‐mercaptopropionyl glycine (MPG) (a simple thiol). 3. The oxidative response of PMA‐stimulated neutrophils measured by lucigenin chemiluminescence was not affected by any of these test agents. The thiol captopril and MPG (but not enalaprilat) caused an initial delay in luminol chemiluminescence production by PMA‐stimulated neutrophils. 4. Captopril and MPG (but not enalaprilat) increased, rather than decreased oxygen uptake, when added to PMA‐stimulated neutrophils. Thiol oxidation was determined to be, at least partly, responsible for the excess oxygen uptake observed. 5. NADPH oxidase activity in intact neutrophils was not affected by captopril, MPG or enalaprilat. The inhibition of NADPH oxidase activity is unlikely to contribute to the therapeutic effects of captopril and other thiols.
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