Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid.

Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not alpha-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-alpha-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.     

Effects of coenzyme Q(10) administration on its tissue concentrations,mitochondrial oxidant generation,and oxidative stress in the rat

Coenzyme Q (CoQ(10)) is a component of the mitochondrial electron transport chain and also a constituent of various cellular membranes. It acts as an important in vivo antioxidant, but is also a primary source of O(2)(-*)/H(2)O(2) generation in cells. CoQ has been widely advocated to be a beneficial dietary adjuvant. However, it remains controversial whether oral administration of CoQ can significantly enhance its tissue levels and/or can modulate the level of oxidative stress in vivo. The objective of this study was to determine the effect of dietary CoQ supplementation on its content in various tissues and their mitochondria, and the resultant effect on the in vivo level of oxidative stress. Rats were administered CoQ(10) (150 mg/kg/d) in their diets for 4 and 13 weeks; thereafter, the amounts of CoQ(10) and CoQ(9) were determined by HPLC in the plasma, homogenates of the liver, kidney, heart, skeletal muscle, brain, and mitochondria of these tissues. Administration of CoQ(10) increased plasma and mitochondria levels of CoQ(10) as well as its predominant homologue CoQ(9). Generally, the magnitude of the increases was greater after 13 weeks than 4 weeks. The level of antioxidative defense enzymes in liver and skeletal muscle homogenates and the rate of hydrogen peroxide generation in heart, brain, and skeletal muscle mitochondria were not affected by CoQ supplementation. However, a reductive shift in plasma aminothiol status and a decrease in skeletal muscle mitochondrial protein carbonyls were apparent after 13 weeks of supplementation. Thus, CoQ supplementation resulted in an elevation of CoQ homologues in tissues and their mitochondria, a selective decrease in protein oxidative damage, and an increase in antioxidative potential in the rat.     

Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants.

The responses to oxidative stress induced by chronic exercise (8-wk treadmill running) or acute exercise (treadmill running to exhaustion) were investigated in the brain, liver, heart, kidney, and muscles of rats. Various biomarkers of oxidative stress were measured, namely, lipid peroxidation [malondialdehyde (MDA)], protein oxidation (protein carbonyl levels and glutamine synthetase activity), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), and endogenous antioxidants (ascorbic acid, alpha-tocopherol, glutathione, ubiquinone, ubiquinol, and cysteine). The predominant changes are in MDA, ascorbic acid, glutathione, cysteine, and cystine. The mitochondrial fraction of brain and liver showed oxidative changes as assayed by MDA similar to those of the tissue homogenate. Our results show that the responses of the brain to oxidative stress by acute or chronic exercise are quite different from those in the liver, heart, fast muscle, and slow muscle; oxidative stress by acute or chronic exercise elicits different responses depending on the organ tissue type and its endogenous antioxidant levels.     

Zinc and the Diabetic Heart

Zinc (Zn) is an essential mineral that is required for various cellular functions. Its abnormal metabolism is related to certain disorders such as diabetic complications. Oxidative stress has been considered as the major causative factor for diabetic cardiomyopathy. Zn has a critical antioxidant action in protecting the heart from various oxidative stresses. Zn deficiency was found to be a risk factor for cardiac oxidative damage and supplementation with Zn provides a significant prevention of oxidative damage to the heart. Diabetes causes a significant systemic oxidative stress and also often is accompanied by Zn deficiency that increases the susceptibility of the heart to oxidative damage. Therefore, there is a strong rationale to consider the strategy of Zn supplementation to prevent or delay diabetic cardiomyopathy. This short article collects the preliminary evidence, based on our own studies and those by others, for a preventive effect of Zn supplementation on diabetes-induced injury to the heart in animals and under in vitro conditions. Possible mechanisms by which Zn supplementation prevents diabetic heart disease are discussed. They include an antioxidant action of Zn, insulin function and metallothionein induction. In the final section, the future of Zn supplementation for diabetic patients is also briefly discussed. Although Zn supplementation has not been clinically used to prevent diabetic complications, because several issues need to be addressed, the fact that Zn supplementation is being used clinically for other disorders encourages us to explore its direct clinical application for the prevention of diabetic cardiomyopathy.     

Influence of dietary vitamin E and C supplementation on vitamin E and C content and thiobarbituric acid reactive substances (TBARS) in different tissues of growing pigs

To investigate the influence and possible interactions of dietary vitamin E and C supplementation on vitamin content of both vitamins and oxidative stability of different pork tissues 40 Large White barrows from 25 kg to 106 kg were allocated to four different cereal based diets: Basal diet (B), dl-alpha-tocopherylacetate + 200 mg/kg (E), crystalline ascorbic acid + 300 mg/kg (C) or both vitamins (EC). At slaughtering samples of liver, spleen, heart, kidney, backfat outer layer, ham and M. tongissimus dorsi were obtained. Growth performance of the pigs and carcass characteristics were not influenced by feeding treatments. Dietary vitamin E supplementation had a significant effect on the vitamin E and alpha-tocopherol concentration in all investigated tissues. Backfat outer layer, liver, spleen, kidney and heart had higher vitamin E concentrations than ham and M. longissimus dorsi. Dietary vitamin C supplementation tended towards enhanced vitamin E levels except for ham samples. Therefore, some synergistic actions without dietary vitamin E supplementation between the two vitamins could be shown. The vitamin C concentration and TBARS were increased or at least equal in all tissues due to vitamin C supplementation. Dietary alpha-tocopherol supplementation resulted in lower TBARS in backfat outer layer (malondialdehyde 0.35 mg/kg in B vs. 0.28 mg/kg in E), but increased in heart and ham. When both vitamins were supplemented (EC) TBARS were lower in M. longissimus dorsi and backfat outer layer, equal in heart and higher in liver and ham compared to a single vitamin C supplementation. Rancimat induction time of backfat outer layer was 0.3 h higher in C compared to B and 0.17 h higher in EC than in E. Correlations between levels of both vitamins were positive for kidney (r = 0.169), M. longissimus dorsi (r = 0.499) and ham (r = 0.361) and negative for heart (r = -0.350). In liver and spleen no interaction could be found. In backfat outer layer vitamin E was positively correlated with rancimat induction time (r = 0.550) and negatively with TBARS (r = -0.202), but provided no evidence that dietary vitamin E supply led to better oxidative stability.     

Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise.

Antioxidant nutrients have demonstrated potential in protecting against exercise-induced oxidative stress. alpha-Lipoic acid (LA) is a proglutathione dietary supplement that is known to strengthen the antioxidant network. We studied the effect of intragastric LA supplementation (150 mg/kg, 8 wk) on tissue LA levels, glutathione metabolism, and lipid peroxidation in rats at rest and after exhaustive treadmill exercise. LA supplementation increased the level of free LA in the red gastrocnemius muscle and increased total glutathione levels in the liver and blood. The exercise-induced decrease in heart glutathione S-transferase activity was prevented by LA supplementation. Exhaustive exercise significantly increased thiobarbituric acid-reactive substance levels in the liver and red gastrocnemius muscle. LA supplementation protected against oxidative lipid damage in the heart, liver, and red gastrocnemius muscle. This study reports that orally supplemented LA is able to favorably influence tissue antioxidant defenses and counteract lipid peroxidation at rest and in response to exercise.     

Antioxidant and oxidative status in tissues of manganese superoxide dismutase transgenic mice

Manganese superoxide dismutase (Mn-SOD) plays an important role in attenuating free radical-induced oxidative damage. The purpose of this research was to determine if increased expression of Mn-SOD gene alters intracellular redox status. Twelve week old male B6C3 mice, engineered to express human Mn-SOD in multiple organs, and their nontransgenic littermates were assessed for oxidative stress and antioxidant status in heart, brain, lung, skeletal muscle, liver, and kidney. Relative to their nontransgenic littermates, transgenic mice had significantly (p <.01) higher activity of Mn-SOD in heart, skeletal muscle, lung, and brain. Copper, zinc (Cu,Zn)-SOD activity was significantly higher in kidney, whereas catalase activity was lower in brain and liver. The activities of selenium (Se)-GSH peroxidase and non-Se-GSH peroxidase, and levels of vitamin E, ascorbic acid and GSH were not significantly different in any tissues measured between Mn-SOD transgenic mice and their nontransgenic controls. The levels of malondialdehyde were significantly lower in the muscle and heart of Mn-SOD mice, and conjugated dienes and protein carbonyls were not altered in any tissues measured. The results obtained showed that expression of human SOD gene did not systematical alter antioxidant systems or adversely affect the redox state of the transgenic mice. The results also suggest that expression of human SOD gene confers protection against peroxidative damage to membrane lipids.     

Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice

Cadmium (Cd) is one of the most important environmental pollutants that cause a number of adverse health effects in humans and animals. Recent studies have shown that Cd-induced oxidative damage within the vascular tissues results in vascular dysfunction. The current study was aimed to investigate whether ascorbic acid could protect against Cd-induced vascular dysfunction in mice. Male ICR mice were received CdCl₂ (100 mg/l) via drinking water for 8 weeks alone or received ascorbic acid supplementation at doses of 50 and 100 mg/kg/day for every other day. Results showed that Cd administration increased arterial blood pressure and blunted the vascular responses to vasoactive agents. These alterations were related to increased superoxide production in thoracic aorta, increased urinary nitrate/nitrite, increased plasma protein carbonyl, elevated malondialdehyde (MDA) concentrations in plasma and tissues, decreased blood glutathione (GSH), and increased Cd contents in blood and tissues. Ascorbic acid dose-dependently normalized the blood pressure, improved vascular reactivities to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP). These improvements were associated with significant suppression of oxidant formation, prevention of GSH depletion, and partial reduction of Cd contents in blood and tissues. The findings in this study provide the first evidence in pharmacological effects of ascorbic acid on alleviation of oxidative damage and improvement of vascular function in a mouse model of Cd-induced hypertension and vascular dysfunction. Moreover, our study suggests that dietary supplementation of ascorbic acid may provide beneficial effects by reversing the oxidative stress and vascular dysfunction in Cd-induced toxicity.     

The effects of endurance training and exhaustive exercise on mitochondrial enzymes in tissues of the rat (Rattus norvegicus)

The aim of the present study was to ascertain the effects of training and exhaustive exercise on mitochondrial capacities to oxidize pyruvate, 2-oxoglutarate, palmitoylcarnitine, succinate and ferrocytochrome c in various tissues of the rat. Endurance capacity was significantly increased (P<0.01) by an endurance training program over a period of 5-6 weeks. The average run time to exhaustion was 214.2+/-23.8 min for trained rats in comparison with 54.5+/-11.7 min for their untrained counterparts. Oxidative capacities were reduced in liver (P<0.05) and brown adipose tissue (P<0.05) as a result of endurance training. On the contrary, the oxidative capacity of skeletal muscle was slightly increased and that of heart almost unaffected except for the oxidation of palmitoylcarnitine, which was significantly reduced (P<0.05) as a result of training.     

Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers

The effects of cadmium on performance, antioxidant defense system, liver and kidney functions, and cadmium accumulation in selected tissues of broiler chickens were studied. Whether the possible adverse effects of cadmium would reverse with the antioxidant ascorbic acid was also investigated. Hence, 4 treatment groups (3 replicates of 10 chicks each) were designed in the study: control, ascorbic acid, cadmium, and cadmium plus ascorbic acid. Cadmium was given via the drinking water at a concentration of 25 mg/L for 6 wk. Ascorbic acid was added to the basal diet at 200 mg/kg either alone or with cadmium. Cadmium decreased the body weight (BW), body weight gain (BWG), and feed efficiency (FE) significantly at the end of the experiment, wheras its effect on feed consumption (FC) was not significant. Cadmium increased the plasma malondialdehyde (MDA) level as an indicator of lipid peroxidation and lowered the activity of blood superoxide dismutase (SOD). Liver function enzymes, aspartate amino transferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT) activities were not changed by cadmium. Cadmium ingestion did not alter serum creatinine levels. Although the serum cadmium level was not elevated, cadmium mainly accumulated in the kidneys, liver, pancreas, and muscle. Ascorbic acid supplementation resulted in a reduction of MDA level previously increased by cadmium and a restoration in SOD activity. However, ascorbic acid did not ameliorate the growth inhibitory effect of cadmium nor did it prevent accumulation of cadmium in analyzed tissues. These data indicate that oxidative stress, induced by cadmium, plays a role in decreasing the performance of broilers and that dietary supplementation by ascorbic acid might be useful in reversing the lipid peroxidation induced by cadmium and partly alleviating the adverse effect of cadmium on performance of broilers.     

Induction of Oxidative Stress by Chronic and Acute Glutaric Acid Administration to Rats

1. Glutaric acidemia type I (GA I) is a neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase, which leads to tissue accumulation of predominantly glutaric acid (GA) and also 3-hydroxyglutaric acid to a lesser amount. Affected patients usually present progressive cortical atrophy and acute striatal degeneration attributed to the toxic accumulating metabolites. 2. In the present study, we determined a number of oxidative stress parameters, namely chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total antioxidant reactivity (TAR), glutathione (GSH) levels, and the activities of catalase and glutathione peroxidase (GPx), in various tissues from rats chronically exposed to GA or to saline (controls). High GA concentrations, similar to those found in glutaric aciduria type I, were induced in the brain by three daily subcutaneous injections of saline-buffered GA (5 μmol/g body weight) to Wistar rats of 5–22 days of life. The parameters were assessed 12 h after the last GA administration in different brain structures, skeletal muscle, heart, liver, erythrocytes, and plasma. The lipid peroxidation parameters chemiluminescence and/or TBA-RS measurements were found significantly increased in midbrain, liver, and erythrocytes of GA-injected rats. The activity of GPx was significantly reduced in midbrain and markedly increased in liver. TAR measurement was significantly reduced in midbrain and liver. Furthermore, GSH levels were reduced in liver and heart. We also investigated the acute in vivo effect of GA administration on the same oxidative stress parameters in cerebral structures and erythrocytes from 22-day-old rats. We found that TBA-RS values were significantly increased in erythrocytes, TAR levels were markedly decreased in midbrain and cerebellum, and GPx activity mildly reduced in the midbrain. 3. These data showing an imbalance between antioxidant defences and oxidative damage, particularly in midbrain, liver, and erythrocytes from GA-injected rats, indicate that oxidative stress might be involved in GA toxicity and that the midbrain, where the striatum is located, is the brain structure more susceptible to GA chronic and acute exposition.     

Influence of dietary vitamin E and C supplementation on vitamin E and C content and thiobarbituric acid reactive substances (TBARS) in different tissues of growing pigs

To investigate the influence and possible interactions of dietary vitamin E and C supplementation on vitamin content of both vitamins and oxidative stability of different pork tissues 40 Large White barrows from 25?kg to 106?kg were allocated to four different cereal based diets: Basal diet (B), dl-α-tocopherylacetate?+?200?mg/kg (E), crystalline ascorbic acid?+?300?mg/kg (C) or both vitamins (EC). At slaughtering samples of liver, spleen, heart, kidney, backfat outer layer, ham and M. longissimus dorsi were obtained. Growth performance of the pigs and carcass characteristics were not influenced by feeding treatments. Dietary vitamin E supplementation had a significant effect on the vitamin E and α-tocopherol concentration in all investigated tissues. Backfat outer layer, liver, spleen, kidney and heart had higher vitamin E concentrations than ham and M. longissimus dorsi. Dietary vitamin C supplementation tended towards enhanced vitamin E levels except for ham samples. Therefore, some synergistic actions without dietary vitamin E supplementation between the two vitamins could be shown. The vitamin C concentration and TBARS were increased or at least equal in all tissues due to vitamin C supplementation. Dietary α-tocopherol supplementation resulted in lower TBARS in backfat outer layer (malondialdehyde 0.35?mg/kg in B vs. 0.28?mg/kg in E), but increased in heart and ham. When both vitamins were supplemented (EC) TBARS were lower in M. longissimus dorsi and backfat outer layer, equal in heart and higher in liver and ham compared to a single vitamin C supplementation. Rancimat induction time of backfat outer layer was 0.3?h higher in C compared to B and 0.17?h higher in EC than in E. Correlations between levels of both vitamins were positive for kidney (r?=?0.169), M. longissimus dorsi (r?=?0.499) and ham (r?=?0.361) and negative for heart (r?=???0.350). In liver and spleen no interaction could be found. In backfat outer layer vitamin E was positively correlated with rancimat induction time (r?=?0.550) and negatively with TBARS (r?=???0.202), but provided no evidence that dietary vitamin E supply led to better oxidative stability.     

Evidence for the influence of vitamin C on age- and heat exposure-dependent deterioration of biochemical function in rat's liver and kidney

Molecular mechanisms responsible for age-dependent deterioration of biochemical functions have not been completely revealed as yet. We studied the role of ascorbic acid food supplementation in young and aged acute heat-exposed rats. The duration of heat exposure (40±0.5 °C) for heat-exposed Wistar rats, at the age of 35 days and 22–24 months, was approximately 2 h. In the aged heat-unexposed animals cholesterol and triglycerides were considerably high, whereas tissues ascorbic acid, glutathione and methylglyoxal were significantly low. Administration of vitamin C reverted these age-associated differences to the status comparable to young rats. The role of vitamin C supplementation was almost the same in young heat-exposed animals. In this direction in young rats suppression of LTC₄ synthesis is evident during acute heat exposure as a result of vitamin C treatment. The importance of vitamin C treatment for young heat-exposed rats is in the protection of apoptosis, if it is determined across the LTC₄ changes. In contrary, in old heat-exposed rats, vitamin C does not suppress the apoptotic processes. The results suggest that oxidative and apoptotic processes in the liver and the kidney as a result of the acute heat exposure is presumably subject of ascorbic acid deficiency.     

Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart

Methionine restriction without energy restriction increases, like caloric restriction, maximum longevity in rodents. Previous studies have shown that methionine restriction strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative damage to mitochondrial DNA, lowers membrane unsaturation, and decreases five different markers of protein oxidation in rat heart and liver mitochondria. It is unknown whether methionine supplementation in the diet can induce opposite changes, which is also interesting because excessive dietary methionine is hepatotoxic and induces cardiovascular alterations. Because the detailed mechanisms of methionine-related hepatotoxicity and cardiovascular toxicity are poorly understood and today many Western human populations consume levels of dietary protein (and thus, methionine) 2–3.3 fold higher than the average adult requirement, in the present experiment we analyze the effect of a methionine supplemented diet on mitochondrial ROS production and oxidative damage in the rat liver and heart mitochondria. In this investigation male Wistar rats were fed either a L-methionine-supplemented (2.5 g/100 g) diet without changing any other dietary components or a control (0.86 g/100 g) diet for 7 weeks. It was found that methionine supplementation increased mitochondrial ROS generation and percent free radical leak in rat liver mitochondria but not in rat heart. In agreement with these data oxidative damage to mitochondrial DNA increased only in rat liver, but no changes were observed in five different markers of protein oxidation in both organs. The content of mitochondrial respiratory chain complexes and AIF (apoptosis inducing factor) did not change after the dietary supplementation while fatty acid unsaturation decreased. Methionine, S-AdenosylMethionine and S-AdenosylHomocysteine concentration increased in both organs in the supplemented group. These results show that methionine supplementation in the diet specifically increases mitochondrial ROS production and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its hepatotoxicity.     

Effect of prolonged exercise on oxidative damage and susceptibility to oxidants of rat tissues in severe hyperthyroidism

We investigated effects of prolonged aerobic exercise and severe hyperthyroidism on indices of oxidative damage, susceptibility to oxidants, and respiratory capacity of homogenates from rat liver, heart and skeletal muscle. Both treatments induced increases in hydroperoxide and protein-bound carbonyl levels. Moreover, the highest increases were found when hyperthyroid animals were subjected to exercise. These changes, which were associated to reduced exercise endurance capacity, were in part due to higher susceptibility to oxidants of hyperthyroid tissues. Levels of oxidative damage indices were scarcely related to changes in antioxidant enzyme activities and lipid-soluble antioxidant concentrations. However, the finding that, following exercise the scavenger levels generally decreased in liver homogenates and increased in heart and muscles ones, suggested a net shuttle of antioxidants from liver to other tissues under need. Aerobic capacity, evaluated by cytochrome oxidase activity, was not modified by exercise, which, conversely, affected the rates of oxygen consumption of hyperthyroid preparations. These results seem to confirm the higher susceptibility of hyperthyroid tissues to oxidative challenge, because the mechanisms underlying the opposite changes in respiration rates during State 4 and State 3 likely involve oxidative modifications of components of mitochondrial respiratory chain, different from cytochrome aa3.     

Ascorbic acid supplementation down-regulates the alcohol induced oxidative stress, hepatic stellate cell activation, cytotoxicity and mRNA levels of selected fibrotic genes in guinea pigs

Both oxidative stress and endotoxins mediated immunological reactions play a major role in the progression of alcoholic hepatic fibrosis. Ascorbic acid has been reported to reduce alcohol-induced toxicity and ascorbic acid levels are reduced in alcoholics. Hence, we investigated the hepatoprotective action of ascorbic acid in the reversal of alcohol-induced hepatic fibrosis in male guinea pigs (n = 36), and it was compared with the animals abstenting from alcohol treatment. In comparison with the alcohol abstention group, there was a reduction in the activities of toxicity markers and levels of lipid and protein peroxidation products, expression of α-SMA, caspase-3 activity and mRNA levels of CYP2E1, TGF-β(1), TNF-α and α(1)(I) collagen in liver of the ascorbic acid-supplemented group. The ascorbic acid content in liver was significantly reduced in the alcohol-treated guinea pigs. But it was reversed to normal level in the ascorbic acid-supplemented group. The anti-fibrotic action of ascorbic acid in the rapid regression of alcoholic liver fibrosis may be attributed to decrease in the oxidative stress, hepatic stellate cells activation, cytotoxicity and mRNA expression of fibrotic genes CYP2E1, TGF-β(1), TNF-α and α(1) (I) collagen in hepatic tissues.     

Short-term ascorbic acid deficiency induced oxidative stress in the retinas of young guinea pigs

We examined whether short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs. Four-week-old guinea pigs were given a scorbutic diet (20 g/animal/day) with and without adequate ascorbic acid (400 mg/animal/day) in drinking water for 3 weeks. The serum concentrations of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 14.1 and 4.1%, respectively, of those in the adequate group. The retinal contents of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 6.4 and 27.3%, respectively, of those in the adequate group. The retinal content of thiobarbituric acid-reactive substances, an index of lipid peroxidation, was 1.9-fold higher in the deficient group than in the adequate group. Retinal reduced glutathione and vitamin E contents in the deficient group were 70.1 and 69.4%, respectively, of those in the adequate group. This ascorbic acid deficiency did not affect serum thiobarbituric acid-reactive substances and reduced glutathione concentrations but increased serum vitamin E concentration. These results indicate that short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs without disrupting systemic antioxidant status.     

Lipid peroxidation and activity of antioxidant enzymes in diabetic rats

We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis of diabetic complications. We therefore investigated the levels of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin (STZ)-induced diabetic rats. The animals were divided into two groups: control and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and liver, heart, pancreas, kidney and blood were collected for measurement of various biochemical parameters. Diabetes was associated with a significant increase in TBARS in pancreas, heart and blood. The activity of CAT increased in liver, heart and blood but decreased in kidney. GSH-Px activity increased in pancreas and kidney while SOD activity increased in liver, heart and pancreas. Our findings suggest that oxidative stress occurs in diabetic state and that oxidative damage to tissues may be a contributory factor in complications associated with diabetes.