Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Influence of treatment of diabetic rats with combinations of pycnogenol, β‐carotene,and α‐lipoic acid on parameters of oxidative stress

Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, β‐carotene, and α‐lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague‐Dawley rats, normal and streptozotocin‐induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, β‐carotene, pycnogenol + β‐carotene, or pycnogenol + β‐carotene + α‐lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with β‐carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) β‐carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:345–352, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20046     

Effects of alpha-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats

Increased oxidative stress and impaired antioxidant defense mechanisms are important factors in the pathogenesis and progression of diabetes mellitus and other oxidant-related diseases. This study was designed to determine whether alpha-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (10 mg/kg ip) once daily for 14 days to normal and diabetic female Sprague-Dawley rats would prevent diabetes-induced changes in biomarkers of oxidative stress in liver, kidney and heart. Serum glucose concentrations, aspartate aminotransferase activity, and glycated hemoglobin levels, which were increased in diabetes, were not significantly altered by alpha-lipoic acid treatment. Normal rats treated with a high dose of alpha-lipoic acid (50 mg/kg) survived but diabetic rats on similar treatment died during the course of the experiment. The activity of glutathione peroxidase was increased in livers of normal rats treated with alpha-lipoic acid, but decreased in diabetic rats after alpha-lipoic acid treatment. Hepatic catalase activity was decreased in both normal and diabetic rats after alpha-lipoic acid treatment. Concentrations of reduced glutathione and glutathione disulfide in liver were increased after alpha-lipoic acid treatment of normal rats, but were not altered in diabetics. In kidney, glutathione peroxidase activity was elevated in diabetic rats, and in both normal and diabetic animals after alpha-lipoic acid treatment. Superoxide dismutase activity in heart was decreased in diabetic rats but normalized after treatment with alpha-lipoic acid; other cardiac enzyme activities were not influenced by either diabetes or antioxidant treatment. These results suggest that after 14 days of treatment with an appropriate pharmacological dose, alpha-lipoic acid may reduce oxidative stress in STZ-induced diabetic rats, perhaps by modulating the thiol status of the cells.     

Effects of beta-carotene on oxidative stress in normal and diabetic rats

Increasing interest in the role of oxidative stress and beta-carotene in disease and prevention led us to examine the results of beta-carotene's administration in diabetic rats, a model for high-oxidative stress. In this experiment, amounts of lipid peroxidation, glutathione, and glutathione disulfide, and activity levels of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and gamma-glutamyl transpeptidase were measured in the liver, kidney, and heart of Sprague-Dawley rats with streptozotocin-induced diabetes, and after treatment with 10 mg/kg/day of beta-carotene for 14 days. Beta-carotene treatment resulted in the reversal of the diabetes-induced increase in hepatic and cardiac catalase activity, the decreased levels of glutathione disulfide in the heart, and the increased cardiac and renal levels of lipid peroxidation. Treatment with beta-carotene exacerbated the increased glutathione peroxidase activity in the heart and the decreased catalase activity in the kidneys. In contrast to reduced hepatic glutathione levels in untreated diabetic rats, beta-carotene treatment increased glutathione levels in diabetic rats. Increased hepatic gamma-glutamyl transpeptidase activity in diabetic rats was not reduced by treatment. Thus, beta-carotene therapy for 14 days prevented/reversed some, but not all, diabetes-induced changes in oxidative stress parameters.     

Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress.

The impairment of nitric oxide (NO)-mediated vasodilation in diabetes has been attributed to increased vascular oxidative stress. Lipoic acid has been shown to have substantial antioxidative properties. The aim of this study was to assess the effect of lipoic acid on NO-mediated vasodilation in diabetic patients in comparison with the well-recognized effect of ascorbic acid. Using venous occlusion plethysmography, we examined the effects of lipoic acid (0.2 mM) and ascorbic acid (1 and 10 mM) on forearm blood flow responses to acetylcholine, sodium nitroprusside and concomitant infusion of the NO-inhibitor, N(G)-monomethyl-L-arginine, in 39 diabetic patients and 11 control subjects. Plasma levels of antioxidants and parameters of lipid peroxidation were measured and correlated to endothelial function tests. Lipoic acid improved NO-mediated vasodilation in diabetic patients, but not in controls. NO-mediated vasodilation was improved by ascorbic acid at 10 mM, but not 1 mM. Improvements of endothelial function by ascorbic acid and lipoic acid were closely related. The beneficial effects of lipoic acid were positively related to plasma levels of malondialdehyde and inversely related to levels of ubiquinol-10. These findings support the concept that oxidative stress contributes to endothelial dysfunction and suggest a therapeutic potential of lipoic acid particularly in patients with imbalance between increased oxidative stress and depleted antioxidant defense.     

Prevention of chromate induced oxidative stress by alpha-lipoic acid

The parenteral administration of alpha-lipoic acid (LA) protected against chromate induced oxidative stress in mouse liver. A shift in Cr induced pro-oxidant state to antioxidant-state by LA was noteworthy. The degree of protection was significant and similar in different LA administration regimens (prior-, co- and post- parenteral Cr exposure) explored. An improved status of the tissue antioxidants by LA appeared to be the mechanism of mitigation. The results are of chemopreventive value and suggest a possible alternative to ascorbic acid for abrogation of Cr toxicity.     

α-亚麻酸对糖尿病大鼠炎症介质和氧化应激的影响

目的:观察α-亚麻酸(ALA)对糖尿病大鼠体内炎症介质和氧化应激的影响,探讨ALA在糖尿病防治中的作用。方法:雄性SD大鼠高脂饮食喂养4周后,腹腔注射链脲佐菌素(STZ)30 mg/kg建立2型糖尿病(T2DM)模型。将大鼠随机分为3组(n=10):正常对照组、糖尿病模型组和ALA治疗组(500μg/kg.d)。4周后测定大鼠血清中肿瘤坏死因子(TNF-α)、可溶性P-选择素(sP-selectin)、可溶性细胞间黏附分子(sICAM-1)、一氧化氮(NO)、丙二醛(MDA)的含量以及超氧化物岐化酶(SOD)和过氧化氢酶(CAT)的活性。结果:与正常对照组相比,糖尿病大鼠血清中炎症介质TNF-α、sP-selectin和sICAM-1的含量增加,血清NO含量下降而MDA升高,同时抗氧化酶SOD和CAT的活性降低;ALA治疗可显著降低糖尿病大鼠血清中TNF-α、sP-selectin和sICAM-1的含量(与STZ+vehicle组相比,P<0.01),增加血清NO水平并减少MDA含量,升高抗氧化酶SOD和CAT的活性(与STZ+vehicle组相比,均P<0.05)。结论:ALA可显著降低糖尿病大鼠血清炎症介质的生成,减轻氧化应激水平,具有抗炎和抗氧化作用。提示ALA对糖尿病及糖尿病并发症的发生发展可能具有一定的防治作用。     

Effects of alpha-lipoic acid on impaired gastric fundus innervation in diabetic rats

Diabetes mellitus is a major cause of neuropathy, leading to adverse effects including autonomic gastrointestinal dysfunction. Oxidative stress contributes to the etiology of diabetic neuropathy. The aim was to examine whether treatment with the antioxidant, alpha-lipoic acid (LA), could prevent or correct diabetic functional defects in the gastric fundus non-adrenergic, non-cholinergic (NANC) nerves, which use nitric oxide as their major neurotransmitter. LA (100 mg/kg/d) was given in a prevention study for 8 weeks following streptozotocin-diabetes induction, and in an intervention study for 4 weeks after 4 weeks of untreated diabetes. Fundus strips were studied in vitro after precontraction with 5-hydroxytryptamine in the presence of guanethidine and atropine to isolate NANC relaxation to electrical field stimulation. After 4 and 8 weeks of diabetes, there were 26% and 48% deficits in maximum relaxation, respectively. Prevention LA treatment gave 83% protection; intervention LA prevented the deterioration between 4 and 8 weeks of diabetes and corrected the initial 4 week deficit by 56%. Diabetes also resulted in a failure to maintain relaxation for prolonged stimulation, which was prevented by LA. Thus, LA prevented and reversed the development of impaired gastric fundus NANC responses in diabetic rats, which has potential therapeutic implications for gastrointestinal autonomic neuropathy.     

Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats.

Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, alpha-lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats. alpha-Lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. alpha-Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by alpha-lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by alpha-lipoic acid (ED(50), 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha-lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of alpha-lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach.     

Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress

In vitro studies have shown that alpha-lipoic acid (LA) is an antioxidant. There is a paucity of studies on LA supplementation in humans. Therefore, the aim of this study was to assess the effect of oral supplementation with LA alone and in combination with alpha-tocopherol (AT) on measures of oxidative stress. A total of 31 healthy adults were supplemented for 2 months either with LA (600 mg/d, n = 16), or with AT (400 IU/d, n = 15) alone, and then with the combination of both for 2 additional months. At baseline, after 2 and 4 months of supplementation, urine for F2-isoprostanes, plasma for protein carbonyl measurement and low-density lipoprotein (LDL) oxidative susceptibility was collected. Plasma oxidizability was assessed after incubation with 100 mM 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 4 h at 37 degrees C. LDL was subjected to copper- and AAPH-catalyzed oxidation at 37 degrees C over 5 h and the lag time was computed. LA significantly increased the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidalion (p < .05), decreased urinary F2-isoprostanes levels (p < .05), and plasma carbonyl levels after AAPH oxidation (p < .001). AT prolonged LDL lag time of lipid peroxide formation (p < .01 ) and conjugated dienes (p < .01) after copper-catalyzed LDL oxidation, decreased urinary F2-isoprostanes (p < .001), but had no effect on plasma carbonyls. The addition of LA to AT did not produce an additional significant improvement in the measures of oxidative stress. In conclusion, LA supplementation functions as an antioxidant, because it decreases plasma- and LDL-oxidation and urinary isoprostanes.     

Changes of oxidative stress parameters in diabetic pregnancy

BACKGROUND: The molecular aetiology of disturbed embryogenesis and other unfavourable outcomes in offspring of diabetic mothers is not fully understood. Experimental studies have suggested an involvement of radical oxygen species (ROS) in the teratological process. THE AIM OF OUR STUDY: To investigate if maternal diabetes in humans is capable of inducing alterations in vascular oxidative stress parameters and whether such changes are associated with disturbances in foetal development. METHODS: Seventy patients with pre-gestational diabetes (PGDM) were chosen for the study: 29 (41.4%) belonged to class B according to White, 15 (21.4%) to class C, 8 (11.4%) to class D, 3 (4.3%) to class F, 3 to class R and 12 (17.1%) to class F/R. In 20 (28.6%) patients from this group an unfavourable outcome was noted. All patients were subjected to intensive insulin therapy. Glycaemia was estimated by daily self-monitoring, and diurnal glucose profiles and glycated haemoglobin (HbA1c) concentrations were measured monthly. Oxidative stress was evaluated as changed superoxide dismutase, catalase and glutathione peroxidase activities as well as of malondialdehyde (MDA) and peroxides concentrations in maternal erythrocytes and blood serum. RESULTS: Prior to conception, the mean glycaemia in the group that had a planned pregnancy was 6.6mmol/l and HBA1c was 9.35%. Throughout the course of pregnancy, these parameters were maintained at a level of 6.7 mmol/l and 7.85%, respectively. The activity of all antioxidative enzymes was lower before than during pregnancy, and so was the concentration of MDA. The MDA concentrations were higher in patients with elevated glycaemia and with an unfavourable outcome. The investigated ROS, the glycaemia level, as well as the concentration of HBA1c did not show any significant differences between pregnancies with and without vascular complications. Patients with a favourable perinatal outcome presented a higher activity of antioxidant enzymes, than those with unfavourable outcome, throughout the whole course of pregnancy. The appearance of unfavourable perinatal outcomes in relation to parameters of oxidative stress was assessed by logistic regression. Both SOD and GPX activities, as well as peroxides' concentration, showed significant correlations (p < 0.005) with foetal complications. However, after mean glucose levels in the studied group were included into these analyses, this relationship was only evident with SOD and GPX activity (p < 0.0016). CONCLUSION: Oxidative stress is one of several important factors contributing to unfavourable outcome of human diabetic pregnancy.     

Ascorbic acid and beta-carotene reduce stress-induced oxidative organ damage in rats

Antioxidants are potential therapeutic agents for reducing stress-induced organ damage. We investigated the effects of ascorbic acid and β-carotene on oxidative stress-induced cerebral, cerebellar, cardiac and hepatic damage using microscopy and biochemistry. Male Wistar albino rats were divided into five groups: untreated control, stressed, stressed + saline, stressed + ascorbic acid and stressed + β-carotene. The rats in the stressed groups were subjected to starvation, immobilization and cold. The histopathological damage scores for the stressed and stressed + saline groups were higher than those of the control group for all organs examined. The histopathological damage scores and mean tissue malondialdehyde levels for the groups treated with antioxidants were lower than those for the stressed and stressed + saline groups. Mean tissue superoxide dismutase activities for groups that received antioxidants were higher than those for the stressed + saline group for most organs evaluated. Ascorbic acid and β-carotene can reduce stress-induced organ damage by both inhibiting lipid oxidation and supporting the cellular antioxidant defense system.     

Early and late effects of hyperbaric oxygen treatment on oxidative stress parameters in diabetic patients

Exposure to hyperbaric oxygen leads to increased amount of reactive oxygen species (ROS) that are derived from various sources. After the discovery that ROS can function as signaling molecules, the idea of ROS being hazardous to biological tissues has been challenged. The aim of this study was to examine the changes in oxidative stress parameters in diabetics undergoing hyperbaric oxygen therapy (HBOT) due to foot ulcers. Twenty patients, who received HBOT for diabetic foot ulcers, were included in the study. Blood samples were taken before HBOT and 30 min after exit from the chamber, on the day of the first and the fifteenth HBOT sessions. They were used for the determinations of malondialdehyde (MDA), 8-isoprostane and advanced oxidation protein products (AOPPs). 8-Isoprostane and AOPP levels were not altered significantly after the first HBOT session, while both were increased on the fifteenth day (p<0.05). MDA was significantly increased only after the first HBOT session, and remained unchanged on the fifteenth day (within-day variations). Plasma AOPP levels were lowered significantly after fifteen consecutive HBOT sessions (between-day variations). Decreased AOPP levels suggest that increased oxygenation of tissues due to HBO therapy may activate some endogenous factors that prevent hazardous effects of the disease itself.     

Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats

Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.     

Impact of tannic acid on blood pressure,oxidative stress and urinary parameters in L-NNA-induced hypertensive rats

Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values (p < 0.01) and urine volumes (p < 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats.     

Effect of beta-carotene and carotene producing yeast Phaffia rhodozyma on oxidative stress in rats treated with tetrachloromethane

Supplementation of rats' diet with beta-carotene or biomass of carotene producing yeast Phaffia rhodozyma caused a decrease of aminotransferases in the blood serum as well as a decrease of lipid peroxidation products and protein carbonil groups in the liver, brain and myocardium tissues of animals treated with tetrachloromethane. When compared to the control group the activity of superoxide dismutase, catalase and glutathione peroxidase in the liver of carotene fed rats were respectively 1.6, 2.2, and 1.5-fold higher. Thus, these supplements to standard diet slow down development of tetrachlorometane mediated oxidative stress in rats.     

Regulation of aging and oxidative stress pathways in aged pancreatic islets using alpha-lipoic acid

Molecular and Cellular Biochemistry - Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study...     

Effects of leptin on oxidative stress in healthy and Streptozotocin-induced diabetic rats

Aims/hypothesis It is generally accepted that oxidative stress is responsible for etiology and complications of diabetes. During uncontrolled Type 1 diabetes, plasma leptin levels rapidly fall. However, it is not known whether diabetes-induced hypoleptinemia has any role in oxidative stress related to uncontrolled Type I diabetes. The present study was designed to examine the effects of leptin treatment on plasma lipid peroxidation and reduced glutathion of normal and streptozotocin(STZ)-induced diabetic rats. Methods Diabetes was induced by single injection of Streptozotocin (55 mg/kg bw). One week after induction of diabetes, rats began 5-day treatment protocol of leptin injections of (0.1 mg/kg bw i.p.) or same volume vehicle. At the end of the 5th day, rats were sacrificed by cardiac puncture under anesthesia and their plasma was taken for plasma leptin, malondialdehyde, and reduced glutathione measurements. Results Plasma leptin levels decreased in STZ-induced diabetic rats while plasma glucose, TBARS, and GSH levels increased. Plasma leptin levels were not affected with leptin treatment in both diabetic and non-diabetic rats. The elevation in plasma TBARS associated with STZ diabetes decreased with leptin treatment. Leptin also increased plasma GSH levels in diabetic rats. In non-diabetic rats, treatment with leptin did not change plasma TBARS and GSH levels. Conclusions/interpretations In conclusion, leptin treatment is able to attenuate lipid peroxidation in STZ-diabetic rats, in the onset of diabetes, by increasing the GSH levels without affecting hyperglycemia and hypoleptinemia.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.