Prooxidant activities of alpha-lipoic acid on oxidative protein damage in the aging rat heart muscle.

In the present study, we investigated whether alpha-lipoic acid (ALA) supplementation could have prooxidant or antioxidant effects on protein oxidation parameters such as protein carbonyl (PCO), nitrotyrosine (NT), advanced oxidation protein products (AOPP), and protein thiol (P-SH), as well as oxidative stress parameters such as total thiol (T-SH), non-protein thiol (Np-SH), and lipid hydroperoxide (LHP) in the heart muscle tissue of aged rats. ALA (100 mg/kg body wt/day) was administered intraperitoneally to the experimental animals for 14 days. PCO, NT, AOPP, and P-SH levels were increased, T-SH and Np-SH levels were not changed, and only LHP levels were decreased in the heart muscle tissue of aged rats with ALA supplementation. When compared with non-supplemented aged rats, increasing levels of protein oxidation markers such as PCO, NT, and AOPP in ALA-supplemented aged rats may suggest that oxidative protein damage is increased in ALA-supplemented aged rats. We assume that an explanation for our findings regarding ALA supplementation on protein oxidation markers in the heart muscle tissue of aged rats may be due to the prooxidant effects of ALA. The prooxidant effects of ALA supplementation should be considered in future studies.

The effects of magnesium sulfate on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

The study was performed to evaluate whether magnesium sulfate could alter the degree of disruption of the blood-brain barrier (BBB) caused by hyperosmotic mannitol. Wistar adult female rats were infused with 25% mannitol into the left internal carotid artery. Each animal received intraperitoneally a 300 mg/kg loading dose of magnesium sulfate, dissolved in 0.9% saline, followed by a further 100 mg/kg dose. In the other group, intracarotid infusion of magnesium sulfate was performed at a dose of 150 mg/kg 10 min before mannitol administration. Evans blue (EB) dye was used as a marker of BBB disruption. The measured serum glucose and magnesium levels increased after mannitol and/or magnesium administration when compared with their initial values before treatment (P < 0.01). Water content of the left hemisphere was significantly increased by hyperosmotic mannitol (P < 0.01). The increased water content in the mannitol-perfused hemisphere was significantly decreased by magnesium treatment (P < 0.05). The content of EB dye in the mannitol-perfused hemisphere markedly increased when compared with the right hemisphere of the same brain (P < 0.01). The EB dye content in the mannitol-perfused hemisphere following both intraperitoneal and intraarterial administration of magnesium decreased when compared with mannitol alone (P < 0.01). We conclude that although magnesium sulfate administration by both intracarotid arterial and intraperitoneal routes attenuates BBB disruption caused by hyperosmolar mannitol, particularly intraperitoneal route of magnesium sulfate administration may provide a useful strategy to limit the transient osmotic opening of the BBB.

Decrease in mitochondrial oxidative protein damage parameters in the streptozotocin-diabetic rat.

BACKGROUND: Many authors have shown that hyperglycemia leads to an increase in oxidative protein damage in diabetes. The aim of this study was to reveal the susceptibility of mitochondria from liver, pancreas, kidney, and skeletal muscle of diabetic Sprague-Dawley rats, a model of type 1 diabetes, to oxidative protein damage. METHODS: Mitochondrial fractions were obtained by differential centrifugation. To show the effect of hyperglycemia in promoting oxidative protein damage, we determined mitochondrial protein carbonyl, total thiol, nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide levels. The levels of the studied markers, except nitrotyrosine, were determined by colorimetric methods. Nitrotyrosine levels were measured by ELISA. All values were compared with those of the controls by using the Mann-Whitney U-test. RESULTS: Nitrotyrosine and lipid hydroperoxide levels were decreased and other parameters were not changed in liver mitochondria of diabetic rats. Protein carbonyl, nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide levels were decreased and total thiol levels were not changed in pancreas mitochondria of diabetic rats. Only advanced oxidation protein products and lipid hydroperoxide levels were decreased in kidney mitochondria of diabetic rats. The levels of the same parameters were not significantly different in muscle mitochondria of diabetic rats. CONCLUSIONS: The decrease in mitochondrial oxidative protein damage in diabetes may correspond to either an increase in antioxidant defense mechanisms or a different adaptive response of the cells to the increased extramitochondrial oxidative stress in diabetes. The mitochondrial oxidative protein damage-lowering mechanisms in diabetes remain to be clarified.

Soluble transferrin receptor and soluble transferrin receptor-ferritin index for evaluation of the iron status in elderly patients.

We aimed to evaluate the diagnostic values of soluble transferrin receptor (sTfR) concentration, transferrin-ferritin index (soluble transferrin receptor concentration/log ferritin), ferritin levels and other related parameters in geriatric patients with anemia of chronic disease (ACD) and iron deficiency (IDA). Forty-four elderly subjects (median age 73 [63-94]) and twenty healthy subjects (median age 49 [44-56]) were enrolled into this study, divided into four groups: twenty middle aged healthy subjects (group A), fifteen elderly patients with IDA (group B), fourteen elderly patients with ACD (group C) and fifteen nonanemic geriatric subjects (group D). Hemoglobin, mean corpuscular volume, serum iron concentration and transferrin saturation levels of the patients in IDA group were found significantly lower than those in both non-anemic group and healthy subjects. Serum sTfR concentrations of the patients in IDA group were significantly higher than those in non-anemic geriatric group, ACD group and healthy subjects. Transferrin-ferritin index of the patients with IDA was significantly higher than that in non-anemic geriatric and ACD group. Serum ferritin levels of the patients in IDA group did not show any differences when compared with the other groups. Serum ferritin was highly specific for IDA (95%) when compared with ACD, although its sensitivity was low (38%). STfR values were negatively correlated with both transferrin and ferritin levels (p = 0.042 r = -0.40; and p = 0.034 r = -0.41, respectively). In conclusion, serum soluble transferrin receptor and transferrin-ferritin index may be used together with serum ferritin to distinguish the iron deficiency state in the elderly.

Relation of aging with oxidative protein damage parameters in the rat skeletal muscle.

OBJECTIVES: An increase in oxidative stress may contribute to the development of oxidative protein damage in the aging rat skeletal muscle. Our aim was to reveal protein carbonyl (PCO), advanced oxidation protein products (AOPP), a novel marker of oxidative stress, and protein thiol (P-SH) levels as markers of protein oxidation, as well as lipid hydroperoxide (LHP) levels as a marker of lipid peroxidation, and relation of nitrotyrosine (NT) levels with these markers in skeletal muscle tissue of young, adult, and old male Wistar rats. DESIGN AND METHODS: In the present study, we investigated the relation between aging and oxidative protein damage parameters such as PCO, NT, AOPP, and P-SH, as well as oxidative stress parameters such as total thiol, nonprotein thiol, and LHP in the skeletal muscle tissue of young, adult, and old Wistar rats. RESULTS: PCO and NT levels of old rats were significantly increased compared with those of young and adult rats. Skeletal muscle AOPP levels were significantly increased in old rats compared with those of adult rats. P-SH levels were significantly decreased in old rats compared with those of young rats. CONCLUSIONS: The finding that the increase in PCO levels of young vs. old group was more significant than that of adult vs. old group may suggest that PCO formation is an early specific marker of aging process in skeletal muscle. In addition, increased levels of nitrotyrosine in the skeletal muscle of the old rat group may be a novel specific marker of oxidative protein damage in the aging muscle. The absence of correlation between oxidative protein damage markers mentioned above and LHP levels may indicate that protein oxidation and lipid peroxidation in the aging rat skeletal tissue are two distinct mechanisms.

Postmenopausal hormone replacement therapy use decreases oxidative protein damage.

OBJECTIVES: The aim of this study is to evaluate oxidative protein damage (OPD) by investigating protein carbonyl (PCO) and nitrotyrosine (NT) levels, oxidative stress by total thiol (T-SH), erythrocyte glutathione (GSH) and nitric oxide (NO) levels in women receiving hormone replacement therapy (HRT). MATERIALS AND METHODS: To examine the influence of oxidative stress on OPD, we studied 12 postmenopausal women who had received HRT for 6 months, and 13 postmenopausal women who did not receive HRT, as the control group. All subjects were non-smokers. Blood samples were drawn in the fasting state and processed within 1 h of collection. For NT and NO, serum samples were stored at -70 degrees C until analysis; all other parameters were determined on the same day of collection. RESULTS: After 6 months, plasma PCO and T-SH levels were decreased, GSH and NO levels were increased, and NT levels were not changed in 12 postmenopausal women receiving HRT. Except the NT levels, the rest of the parameters did not significantly change in the control group. Interestingly, mean NT levels in the control group increased significantly. CONCLUSIONS: A crucial part of the protective effect of HRT on the cardiovascular system arises secondary to the interaction between estrogen and vessel wall. Our results suggest that an important component of the mechanism underlying this interaction may depend on estrogen's antioxidant effect and its preventive role in OPD.