Lysate Thiol Research Articles

Effects of Atenolol, Labetalol and Methyldopa on Endogenous Antioxidants In-vitro

Abstract The aim of this study was to investigate whether atenolol, labetalol and methyldopa, which are commonly used for the treatment of hypertension in pregnancy, can induce antioxidant activity. Reactive oxygen species scavengers (plasma thiol, red cell lysate thiol, red cell superoxide dismutase, red cell membrane thiol and plasma glutathione) were measured after incubation of peripheral blood with atenolol and methyldopa, respectively. The results showed that atenolol and labetalol could significantly raise the levels of plasma thiol and membrane thiol but had no effects on lysate thiol, superoxide dismutase and glutathione. The effects on membrane thiol occurred after 60 min incubation and on plasma thiol after 120 min incubation. The data also suggest that atenolol and labetalol at lower concentrations tend to have additive effects on reactive oxygen species scavengers but at higher concentrations do not. Methyldopa had no significant effect on any of the parameters measured. These findings suggest that atenolol and labetalol are able to induce higher levels of antioxidant activity.

Antioxidants: their role in pregnancy and miscarriage.

The aim of this study was to examine the role of antioxidants within the normal menstrual cycle, in healthy pregnancy, and in women suffering first-trimester miscarriage. The antioxidants chosen comprised of two from peripheral blood-plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels varied little throughout the menstrual cycle. Pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first trimester. These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in their first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage. Miscarriage and pregnancy appear to be associated with increased oxidative stress. In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attack.

Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves’ disease during therapy

Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. We investigated the prooxidant–antioxidant status in order to evaluate the possible deleterious role of oxidative phenomena in patients with Graves’ disease. Thirty patients with hyperthyroidism due to Graves’ disease were investigated. Thirty age-matched healthy subjects were studied as a control group. Free radical activity indices, antioxidant defense systems, and thyroid and pituitary hormone levels were measured in fasting blood samples. Blood samples were taken before initiation of therapy and after attainment of euthyroid state. A significant increase in lipid peroxidation activity indices, i.e., conjugated dienes and thiobarbituric acid-reacting substances, was found in blood serum of the patients with untreated Graves’ disease. These changes were accompanied by a decrease in plasma thiol and erythrocyte lysate thiol groups concentrations. Hyperthyroidism resulted in a marked increase in intracellular antioxidant enzymes, i.e., superoxide dismutase, catalase and glutathione peroxidase activities as compared to the controls. Extracellular anti-free radical scavenging systems potential, measured by glutathione reductase activity and total antioxidant status level, was found to be significantly decreased in untreated Graves’ patients. Treatment with thiamazole resulted in normalization of the free radical and antioxidant activity indices. The obtained results indicate an enhanced generation of reactive oxygen species and impairment of cellular and extracellular antioxidant systems potential in patients with Graves’ disease. The attainment of euthyroid state led to an improvement in oxidative stress indices and antioxidant potential parameters.

Altered Thiol Status in Preeclampsia

Thirty preeclamptic, 30 normotensive pregnant and 25 healthy nonpregnant women were analyzed with regard to the antioxidant system (thiols and superoxide dismutase, SOD). In preeclampsia both plasma and lysate thiol levels were significantly lower compared to controls (p < 0.001). SOD levels were higher in normotensive pregnant women, but were lower in preeclamptic compared to nonpregnant women. This finding of antioxidant changes in the red blood cell suggests that red cell dysfunction is fundamental in the development of preeclampsia, and similar alterations in the balance of the thiol could be present across the endothelial cell membrane.

Evidence for Carbimazole as an Antioxidant?

There is evidence in the literature to support the view that antioxidants are involved in the pathogenesis of Graves disease and that antioxidants may act as free radical scavengers. This study has compared the effects of a 12 month course of conventional Carbimazole therapy on peripheral blood antioxidant levels with those of a 12 month course of a higher dose treatment regime. Fifty seven patients were enrolled into the study. Those in Group 1 (n = 23) received a 12 month course of 60 mg/day Carbimazole. Those in Group 2 (n = 34) received 45 mg/day for the first month, 30 mg/day for the second and 20 mg/day for the remaining 10 months of treatment. T3 was added in both groups after 2-4 months to maintain patients euthyroid. Baseline samples were also obtained from 30 control subjects. Blood samples were taken for the measurement of plasma thiol (PSH), lysate thiol (LSH), superoxide dismutase (SOD) and caeruloplasmin (CP) and for routine thyroid function tests (TT4, TT3 and TSH).In untreated Graves' patients, serum levels of PSH and SOD were reduced and levels of LSH increased compared to controls. Following 2 months high dose Carbimazole therapy there was a significant increase in PSH levels and a significant reduction in CP levels compared to presentation levels. In the more conventional dose Group 2 patients PSH levels also rose significantly during the first 2 months of treatment. Levels for both groups were still significantly lower than the control group. After 12 months high dose Carbimazole therapy PSH levels had decreased so that they no longer differed from untreated levels. LSH and SOD levels still remained abnormal. CP levels continued to fall. Similar findings were obtained in those patients receiving the more conventional course of treatment. At no point was their any significant difference in antioxidant levels between the two treatment groups.The abnormal levels of antioxidants in the serum of untreated Graves' patients confirm their involvement in the pathogenesis of Graves' disease. Carbimazole therapy appeared to have only short term effects on the peripheral blood levels of the antioxidants measured.Carbimazole appeared to act only on the extra cellular markers of antioxidant activity (PSH, CP) although the disease itself had marked intracellular effects (LSH, SOD). These findings suggest that Carbimazole does not act as a free radical scavenger.

Antioxidants and Immunological Markers in Pregnancy-Induced Hypertension and Essential Hypertension in Pregnancy

The aim of this study was to investigate whether there was any difference in the levels of antioxidant agents in the immune system between essential hypertension in pregnancy and pregnancy-induced hypertension (PIH). The functions of T and B lymphocytes were analysed by lymphocyte response to mitogens and the ability to secrete immunoglobulins, respectively. Interleukin-2 (IL-2) production from lymphocytes was also determined by bioassay. Five antioxidant agents–superoxide dismutase (SOD), plasma thiol (PSH), red cell lysate thiol (LSH), plasma glutathione (GSHp) and red cell membrane thiol (MSH)–were measured enzymatically and spectrophotometrically. The results showed that there was no significant difference in mitogenic activity between normal pregnancy and essential hypertension. However, phytohaemagglutinin-induced mitogenic activity was increased in patients with PIH compared to patients with essential hypertension and normal pregnancy. IL-2 production in patients with PIH was also significantly hig...

Calcium channel blockers and antioxidant levels

SUMMARY The aim of this study was to determine in vitro whether calcium channel blockers (nifedipine and nimodipine) exert their antiperoxidative effect by changing the antioxidant levels. Four antioxidant markers in red blood cells were investigated: membrane thiol, lysate thiol, lysate total glutathione and lysate superoxide dismutase. These antioxidant markers were measured after cells were incubated with varying concentrations of nifedipine and nimodipine (1–1000 ng/ml) for different time periods (0–120 min). The results showed that neither nifedipine nor nimodipine significantly increased antioxidant levels. In conclusion, it appears that calcium channel blockers are unable to elevate the levels of the physiological antioxidant agents detected in this in vitro experiment.

Prostacyclin, thromboxane and antioxidant levels in pregnancy-induced hypertension

1. Plasma 6-keto-prostaglandin F 1α (6-keto-PGF 1α, a major metabolite of prostacyclin), plasma thromboxane B 2 (TXB 2, a major metabolite of thromboxan A 2) and five antioxidants (indirect markers of reactive oxygen species) namely, plasma thiol, erythrocyte lysate thiol, erythrocyte superoxide dismutase, plasma total gluthathione and erythrocyte membrane thiol, were measured in 25 healthy non-pregnant women, 36 normotensive pregnant women and 35 women with pregnancy-induced hypertension (PIH). 2. The levels of TXB 2 were significantly increased in normal pregnant women and PIH women with or without proteinuria compared with non-pregnant women. The concentrations of TXB 2 in PIH women with proteinuria were higher than those without proteinuria ( P < 0.05). 3. The levels of 6-keto-PGF 1α in healthy non-pregnant women and PIH women with or without proteinuria were significantly lower than that in normotensive pregnant women (all of three P < 0.01). There were no significant differences between healthy non-pregnant women and PIH women with and without proteinuria. 4. The ratio of TXB 2 to 6-keto-PGF 1α was markedly elevated in PIH women with or without proteinuria compared with normotensive pregnant women and healthy non-pregnant women. The difference between PIH women with proteinuria and those without proteinuria was not significant ( P > 0.05). 5. The levels of plasma thiol, superoxide dismutase and glutathione were significantly decreased in PIH women compared with normotensive pregnant women. 6. There were significant positive correlations between the levels of prostaglandins and antioxidant activity. 7. These results demonstrate that there is an imbalance between TXB 2 and 6-keto-PGF 1α in women with PIH and decreased antioxidant levels which may reflect an increased activity of reactive oxygen species. The data suggest that the changes in the activity of reactive oxygen species may have a causative role in the abnormal pattern of TXA 2 and PGI 2 production in patients with PIH.

Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension

Increased free radical activity has been implicated in the pathogenesis of pregnancy-induced hypertension. This article investigates whether changes in antioxidant systems contribute to this condition. Two extracellular (plasma thiols and ceruloplasmin) and two intracellular (red blood cell lysate thiols and red blood cell superoxide dismutase) antioxidant markers were assayed in 25 nonpregnant women, 16 pregnant women with normal blood pressure, 19 women with pregnancy-induced hypertension, and 13 women with proteinuric pregnancy-induced hypertension. In the normotensive pregnant group (in comparison with the nonpregnant group) the plasma thiol level was reduced (p < 0.001) and the ceruloplasmin level raised (p < 0.005), suggesting increased free radical activity. The lysate thiol level increased (p < 0.005), which may reflect a compensatory protective response. In the hypertensive pregnant groups the lysate thiol rise was not present. These red blood cells may be more prone to oxidative stress. Whether this situation is a cause or an effect of oxidative stress in pregnancy-induced hypertension has yet to be elucidated. (AM J OBSTET GYNECOL 1991;165:1701-4.)

Free Radical Activity in Type 2 Diabetes

Free radical activity has been implicated in the development of diabetic vascular complications in Type 1 diabetes. The aim of the present study was to investigate the levels of free radical scavengers, particularly erythrocyte superoxide dismutase, plasma and erythrocyte lysate thiol, and caeruloplasmin in 22 Type 2 diabetic patients clinically free of complications, and 15 comparable non-diabetic control subjects. The concentration (median (range] of both superoxide dismutase (23 (10-39) vs 45 (25-75) mumol l-1; p less than 0.001) and plasma thiol (374 (172-523) vs 460 (386-595) mumol l-1; p less than 0.01) were reduced in the diabetic group. There were no significant differences in the concentration of erythrocyte lysate thiol (199 (114-520) vs 188 (114-328) mumol l-1) or plasma caeruloplasmin (18 (9-31) vs 24 (6-50) mumol l-1) between the groups. This reduction in superoxide dismutase and the imbalance in the redox status of the plasma and lysate thiol demonstrated is consistent with an increase in free radical activity in Type 2 diabetes.

Free radicals and Graves' disease: the effects of therapy.

Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change. All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red-cell membrane. In addition LSH is a general radical scavenger and SOD a specific O2- scavenger. In Graves' disease the increased oxidative stress and increased general radical scavenging may result from raised free-radical activity. These changes, which have not previously been reported in Graves' patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect.