Effect of vitamin E on oxidative stress status in small intestine of diabetic rat

AIM:To investigate the effect of vitamin E on oxidative stress status in the small intestine of diabetic rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups:Control (C),non-treated diabetic (NTD) and vitamin E-treated diabetic (VETD) groups. The increases in lipid peroxidation,protein oxidation and superoxide dismutase (SOD) in these three groups was compared after 6 wk. RESULTS:There was no significant difference in catalase activity between NTD and control rats. Compared to NTD rats,the treatment with vitamin E significantly decreased lipid peroxidation and protein oxidation,and also increased catalase activity and SOD. CONCLUSION:The results revealed the occurrence of oxidative stress in the small intestine of diabetic rats. Vitamin E,as an antioxidant,attenuates lipid peroxidation and protein oxidation,and increases antioxidant defense mechanism.     

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

AIM： To investigate the effects of vitamins （A, C and E） on liver injury induced by ethanol administration during liver regeneration in rats. METHODS： Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups （groups 1-5）. During the experiment, animals of Group 1 drank only water. The other four groups （2-5） drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin and bilirubin were measured colorimetrically. Lipid peroxidation （thiobarbituric-acid reactive substances, TBARS） both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS： Compared with sham group, serum AST and ALT increased significantly under ethanol treatment （43% and 93%, respectively, with P 〈 0.05）. Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group （3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P 〈 0.05）. During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation （4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P 〈 0.05）. In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins （C and E） treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION： Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.     

Heme Oxygenase Induction Protects Liver Against Oxidative Stress in X-Irradiated Aged Rats

We studied the effect of total body X-ray irradiation on the heme oxygenase-1 (HO-1) induction in the livers of young and aged rats. For this purpose, male rats were irradiated with a dose of 17 Gy. The animals were killed 5 h after irradiation. HO-1 protein expression was found to be increased two fold in aged rat liver, but lipid peroxide levels had decreased significantly where no change was observed either in inducible nitric oxide synthase protein expression or in glutathione levels. Contradictory results with respect to HO-1 and lipid peroxidation levels were obtained in the livers of young animals. These results suggest that the additional oxidative stress produced in irradiated rats may be compensated by HO-1 induction as decreased lipid peroxide levels were shown in the livers of aged animals.     

Lipid peroxidation in lung of rat stressed by immobilization: Effects of vitamin E supplementation

This study was carried out to examine the possibility of initiation of lipid peroxidation in the lung of Wistar albino male rats stressed by immobilization. The effects of vitamin E supplementation were also investigated. We found that immobilization of rats with normal pulmonary content of vitamin E caused lipid peroxidation in the lung. Decrease of the lung content of unsaturated fatty acids and vitamin E was also established. The immobilization-induced changes of all of these parameters were significantly inhibited by vitamin E injection (100 mg/kg body weight) for 7 days. A possible sequence of events leading to the initiation of lipid peroxidation and lung cell membrane damage in rats stressed by immobilization is discussed. Offprint requests to: Stefan Ribarov, PhD     

Relative inactivation of steroidogenic enzyme activities of in vitro vitamin E-depleted human adrenal microsomes by lipid peroxidation

The effects of lipid peroxidation and vitamin E on the steroidogenic activities of human adrenal microsomes were studied. The vitamin E content in the microsomes could be varied by treating the lyophilized microsomes with n-pentane, without affecting the steroidogenic enzyme activities. When the level of microsomal vitamin E in the adrenal was reduced to that in other tissues such as liver and kidney, NADPH-supported lipid peroxidation increased about 200-fold, and concomitantly, the steroidogenic enzyme activities decreased. After 5 min of the lipid peroxidation reaction, 17 alpha-hydroxylase and C17,20-lyase activities were inactivated to 13% and 18%, respectively, of the original activities. 3 beta-Hydroxysteroid dehydrogenase-isomerase and 21-hydroxylase, however, retained 89% and 84%, respectively, of the original activities. When vitamin E was reincorporated into the original activities. When vitamin E was reincorporated into the extracted microsomes, neither the lipid peroxidation reaction nor the inactivation of the enzyme activities was observed. These results indicate that the high concentration of vitamin E in adrenal protects the enzymes from oxidative damage, and that the microsomal C19 steroidogenic cytochrome P-450 activities are highly sensitive to lipid peroxidation. This suggests an association between adrenal lipid peroxidation and a decrease in C19 steroid synthesis with advancing age.     

Lipid peroxidation product 4-hydroxy-2-nonenal acts synergistically with serotonin in inducing vascular smooth muscle cell proliferation

Formation of an atherosclerotic lesion is in part mediated by inflammatory and oxidative mechanisms including lipid peroxidation. To characterize the potential role of lipid peroxidation products in atherogenesis, we assessed the effect of 4-hydroxy-2-nonenal (HNE), a component of oxidatively modified lipids on vascular smooth muscle cells (VSMCs) proliferation, and its interaction with serotonin (5-hydroxytryptamine, 5-HT), a known mitogen for VSMCs. Growth-arrested rabbit VSMCs were incubated with different concentrations of HNE in the absence or presence of 5-HT. VSMCs proliferation was examined by increases in [3H]thymidine incorporation into DNA and cell number. HNE and 5-HT stimulated DNA synthesis in a dose-dependent manner. HNE had a maximal proliferative effect at a concentration of 1 microM (143% of the control) and 5-HT at 50 microM (211%). When added together, low concentrations of HNE (0.1 microM) and 5-HT (5 microM) synergistically induced DNA synthesis (273%). These effects on DNA synthesis were paralleled by an increase in cell number. A 5-HT2 receptor antagonist LY 281067 (10 microg/ml) and pertussis toxin (10 ng/ml) inhibited the mitogenic effect of 5-HT only. Protein tyrosine kinase inhibitor erbstatin A (10 microM) completely inhibited the mitogenic effect of HNE and partially that of 5-HT and the combined effect of HNE+5-HT. Protein kinase C inhibitor Ro 31-8220 (0.1 microM) completely inhibited mitogenic effects of both HNE and 5-HT, and also the combined effect of HNE+5-HT. The synergistic effect of HNE+5-HT on DNA synthesis was completely reversed by the combined use of LY 281067 (10 microg/ml) and antioxidants N-acetylcysteine (400 microM), vitamin C (200 microM), or vitamin E (20 microM). Our results suggest that HNE acts synergistically with 5-HT in inducing VSMCs proliferation. Combined use of both antiplatelet and antioxidant therapies may be useful for the prevention of VSMCs proliferative disorders associated with atherosclerosis and restenosis after angioplasty.     

Effects of ethanol on antioxidant capacity in isolated rat hepatocytes

AIM: To investigate dose-response and time-course of the effects of ethanol on the cell viability and antioxidant capacity in isolated rat hepatocytes. METHODS: Hepatocytes were isolated from male adult Wistar rats and seeded into 100-mm dishes. Hepatocytes were treated with ethanol at concentrations between 0 (C), 10 (E10), 50 (E50), and 100 (E100) mmol/L (dose response) for 12, 24, and 36 h (time course). Then, lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) concentration, glutathione (GSH) level, and activities of glutathione peroxidase (GPX), glutathione reductase (GRD), superoxide dismutase (SOD), and catalase (CAT) were measured. RESULTS: Our data revealed that LDH leakage was significantly increased by about 30% in group E100 over those in groups C and E10 at 24 and 36 h, The MDA concentration in groups C, E10 and E50 were significantly lower than that in group E100 at 36 h. Furthermore, the concentration of MDA in group E100 at 36 h was significantly higher by 4.5- and 1.7-fold, respectively, than that at 12 and 24 h. On the other hand, the GSH level in group E100 at 24 and 36 h was significantly decreased, by 32% and 28%, respectively, compared to that at 12 h. The activities of GRD and CAT in group E100 at 36 h were significantly less than those in groups C and E10. However, The GPX and SOD activities showed no significant change in each group. CONCLUSION: These results suggest that longtime incubation with higher concentration of ethanol (100 mmol/L) decreased the cell viability by means of reducing GRD and CAT activities and increasing lipid peroxidation.     

Potentiation of acute paraquat toxicity by vitamin E deficiency

The present study evaluated the development and course of acute paraquat toxicity in rats deficient in vitamin E, a major biologic antioxidant which interrupts free radical chain reactions and blocks lipid peroxidation. Normal and vitamin E deficient rats were given 50 mg/kg paraquat dichloride in a single intraperitoneal (IP) injection. Both percent survival and duration of survival following paraquat were significantly reduced in vitamin E deficient rats. Only 1 (2.5%) of 40 vitamin E deficient rats survived 14 days compared to 12 (30%) of 40 (p < 0.001) normal rats, and deaths occurred much earlier (p < 0.001) in vitamin E deficient rats. In addition, histologic lung damage 24 to 48 h after paraquat administration was far more extensive in vitamin E deficient rats than normal rats. Vitamin E deficient rats treated (i. e., repleted) for 7 days prior to paraquat with vitamin E 1 mg/kg/day IP had a survival rate and duration of survival nearly identical to normal rats receiving paraquat. In contrast, vitamin E deficient rats treated for 3 days prior to and 3 days after paraquat administration with superoxide dismutase (SOD) 10 mg/kg bid IP had survival rates and lung histologic changes indistinguishable from vitamin E deficient rats not receiving SOD. These results (1) demonstrate that deficiency of vitamin E potentiates acute paraquat toxicity in rats, (2) indicate that this potentiation is readily reversed by administration of vitamin E but not SOD, and (3) provide in vivo evidence that paraquat toxicity may be mediated through lipid peroxidation.     

Cardiac reperfusion injury: Aging, lipid peroxidation, and mitochondrial dysfunction

Cardiac reperfusion and aging are associated with increased rates of mitochondrial free radical production. Mitochondria are therefore a likely site of reperfusion-induced oxidative damage, the severity of which may increase with age. 4-Hydroxy-2-nonenal (HNE), a major product of lipid peroxidation, increases in concentration upon reperfusion of ischemic cardiac tissue, can react with and inactivate enzymes, and inhibits mitochondrial respiration in vitro. HNE modification of mitochondrial protein(s) might, therefore, be expected to occur during reperfusion and result in loss in mitochondrial function. In addition, this process may be more prevalent in aged animals. To begin to test this hypothesis, hearts from 8- and 24-month-old rats were perfused in Langendorff fashion and subjected to periods of ischemia and/or reperfusion. The rate of state 3 respiration of mitochondria isolated from hearts exposed to ischemia (25 min) was approximately 25% less than that of controls, independent of age. Reperfusion (40 min) caused a further decline in the rate of state 3 respiration in hearts isolated from 24- but not 8-month-old rats. Furthermore, HNE modification of mitochondrial protein (~30 and 44 kDa) occurred only during reperfusion of hearts from 24-month-old rats. Thus, HNE-modified protein was present in only those mitochondria exhibiting reperfusion-induced declines in function. These studies therefore identify mitochondria as a subcellular target of reperfusion damage and a site of age-related increases in susceptibility to injury.     

刺梨汁拮抗慢性氟中毒的实验观察

用含氟３２０ｍｇ／ｋｇ饲料和含维生素Ｃ６００ｍｇ／１００ｍｌ刺梨汁饮不饲养Ｗｉｓｔａｒ大鼠６个月，探讨刺梨汁对慢性氟中毒的影响及其机理。结果发现刺梨汁具有明显改善慢性氟中毒的一般状况，减少氟斑牙的形成，增加氟中毒大鼠的体重，促进尿氟排泄，降低血清和骨氟含量，提高血清维生素Ｃ含量，保护胶原组织，使尿羟脯氨酸含量降低，通过提高血清维生素Ｅ和ＧＳＨ含量，增强血ＧＳＨ－Ｐｘ和ＳＯＤ活性而抑制氟中毒引起的脂     

Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus

There is a clearly documented link between diabetic complications and lipid peroxidation. Hyperglycemia causes a reduction in levels of protective endogenous antioxidants and increases generation of free radicals. The present study was carried out to compare the protective effects of melatonin and vitamin E against streptozocin (STZ)-induced diabetes in rats. Melatonin was administered s.c. (100 microg/kg) whereas vitamin E was given i.p. (100 mg/kg) after induction of diabetes with STZ (60 mg/kg). Plasma total cholesterol, triglyceride and low density lipoprotein (LDL) levels were increased in STZ group while both melatonin and vitamin E injection caused a significant decrease in the levels of all these parameters. The lipid lowering effect of melatonin was greater than that of vitamin E. Melatonin caused a significant decrease in brain, liver and kidney tissue malondialdehyde (MDA) levels which were increased because of STZ-induced diabetes. Vitamin E also reduced elevated MDA concentrations in diabetic rat tissues, but the effect of melatonin was more potent than that of vitamin E. Furthermore, treatment of diabetic rats with melatonin increased brain and kidney glutathione peroxidase (GSH-Px) activity to the levels below that of control rats. Vitamin E was found to be less effective on GSH-Px activity levels in brain and kidney than melatonin whereas it was more potent than melatonin in liver. In summary, melatonin prevents many diabetic complications by reducing oxidative stress and protects organisms from oxidative damage and dyslipidemia. Considering the much lower molar concentration of melatonin compared with vitamin E, melatonin seems to be a more potent antioxidant, especially in the brain and kidney.     

Lipid peroxidation and antioxidant defense systems in rat liver after chronic ethanol feeding

The effects of chronic ethanol feeding on hepatic lipid peroxidation, ascorbic acid, glutathione and vitamin E levels were investigated in rats fed low or adequate amounts of dietary vitamin E. Hepatic lipid peroxidation was significantly increased after chronic ethanol feeding in rats receiving a low-vitamin E diet, indicating that dietary vitamin E is an important determinant of hepatic lipid peroxidation induced by chronic ethanol feeding. No significant change was observed in hepatic non-heme iron content, but hepatic content of ascorbic acid and glutathione was increased by ethanol feeding. Both low dietary vitamin E and ethanol feeding significantly reduced hepatic alpha-tocopherol content, and the lowest hepatic alpha-tocopherol was found in rats receiving a combination of low vitamin E and ethanol. Plasma alpha-tocopherol was elevated after ethanol feeding, probably because of the associated hyperlipemia. Both the ratio of plasma alpha-tocopherol/plasma lipid and the red blood cell alpha-tocopherol were reduced by ethanol feeding. Furthermore, ethanol feeding caused a marked increase of hepatic alpha-tocopheryl quinone, a metabolite of alpha-tocopherol by free radical reactions. Ethanol feeding caused little changes of alpha-tocopherol and alpha-tocopheryl quinone content in mitochondria, whereas a striking increase in alpha-tocopheryl quinone was observed in microsomes. These data suggest that ethanol feeding causes a marked alteration of vitamin E metabolism in the liver and that the combination of ethanol with a low-vitamin E intake results in a decrease of hepatic alpha-tocopherol content which renders the liver more susceptible to free radical attack.     

Increased Lipid Peroxidation of Erythrocytes in Blood Stored in Polyvinyl Chloride Blood Storage Bags Plasticized with Di-[2-Ethyl Hexyl] Phthalate and Effect of Antioxidants

Background and Objectives : Previous work in this laboratory has shown significant decrease in vitamin E in erythrocytes in blood stored in polyvinyl chloride (PVC) bags plasticized with di-[2-ethyl hexyl] phthalate (DEHP), and in erythrocytes incubated in vitro with DEHP. Since vitamin E is a major antioxidant, a study was carried out to find out whether this decrease observed in vitamin E has an effect on lipid peroxidation in blood stored in DEHP-plasticized PVC blood bags. Materials and Methods : Blood was collected in Penpol blood storage bags (which is a DEHP-plasticized PVC bag) and parameters of lipid peroxidation, i.e. activity of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, concentration of malondialdehyde (MDA), conjugated dienes, hydroperoxides, glutathione and vitamin E studied in erythrocytes after various periods of storage as compared to glass bottles. Erythrocytes were also incubated in vitro with DEHP with and without vitamin E, and changes in lipid peroxidation studied. Results :Blood stored in Penpol bags showed increased lipid peroxidation in erythrocytes as compared to that stored in glass bottles, as is evident from a greater increase in MDA and a greater decrease in glutathione and a significant decrease in vitamin E. The addition of vitamin E decreased the formation of MDA and conjugated dienes and prevented the decrease in vitamin E. However in spite of increased lipid peroxidation in the presence of DEHP, the release of K⁺ and hemoglobin from erythrocytes was lower. When there was an increase in DEHP taken up by erythrocytes, there was a corresponding decrease in vitamin E. More important, whenever there was an increase in vitamin E in erythrocytes (when RBCs in the presence of DEHP were incubated with vitamin E), there was a progressive decrease in DEHP. Conclusion : DEHP caused increased lipid peroxidation in erythrocytes. At the same time, it decreased the release of K⁺ and hemoglobin from erythrocytes. It is possible that the stabilizing effect of DEHP on the erythrocyte membrane may offset the detrimental effects of the increased lipid peroxidation it causes.     

Cerulein-induced acute pancreatitis diminished vitamin E concentration in plasma and increased in the pancreas

Summary Redistribution of vitamin E in the rat body was studied during acute pancreatitis induced by two intraperitoneal doses of cerulein 40 μg/kg of body weight at 1-hr intervals. Hyperamylasemia (2064±521 vs 6419±129 U/dL) and pancreatic edema (pancreatic water content, 71±1.2% vs 78±2%) were observed. In this model the increased level of lipid soluble fluorophore was also observed (274±18 vs 120±9.0 relative fluorescence per g dry wt). Parallel with these changes was a decrease in the level of vitamin E in the serum and an increase in the pancreas. The concentration of vitamin E in the pancreas after 6h was 162±8.5 ng/mg dry mass vs 128.1 ±6.1 ng/mg dry mass in control animals. The effect of heparin on vitamin E redistribution induced by acute pancreatitis was also investigated. It was found that heparin at a dose of 100 U/kg body mass prevents the drop of the vitamin E level in the serum as well as the increases in the concentration in the pancreas tissue. It was concluded that acute pancreatitis induced redistribution of vitamin E in the rat body. Moreover, we studied the effects of heparin treatment on oxidative stress in the pancreas tissue. Acute pancreatitis caused an increase in lipofuscin accumulation, and a decrease in protein sulfhydryl groups in citrate synthetase (CS) and in malate dehydrogenase (MDH) activity. Heparin treatment that protected vitamin E accumulation in the pancreas tissue did not influence the changes in the level of lipofuscin and proteins sulfhydryl. On the other hand rats treated with heparin showed a greater decrease in CS and MDH activities.     

Dietary fish oil does not prevent doxorubicin-induced cardiomyopathy in rats

BACKGROUND: Dietary fish oil potentiates the susceptibility of cellular membranes to lipid peroxidation, although it is also known to have beneficial effects on the development of cardiovascular diseases. OBJECTIVE: The effects of dietary fish oil against doxorubicin-induced cardiomyopathy, in which free radicals and lipid peroxidation are involved, were investigated in rats. ANIMALS AND METHODS: Sprague-Dawley rats (100 g) were fed a standard diet or a high fish oil diet (containing 10% fish oil) throughout the experimental period. Four weeks after starting each diet, experimental rats were treated with doxorubicin (cumulative dose 15 mg/kg) or vehicle (0.28 M dextrose solution). After three weeks of doxorubicin treatment, the cardiac performance, myocardial lipid peroxidation and myocardial vitamin E level were assessed. RESULTS: Compared with control rats, doxorubicin-treated rats showed a significantly increased mortality rate (P<0.05), and significantly decreased systolic blood pressure and left ventricular fractional shortening (P<0.01). The myocardial thiobarbituric acid-reactive substance level was significantly higher in doxorubicin-treated rats than in control rats (P<0.01), while the myocardial vitamin E level was significantly lower (P<0.05). Dietary fish oil enhanced the myocardial lipid peroxidation caused by doxorubicin, which was associated with a further decrease in myocardial vitamin E level. As a result, the rats treated with both doxorubicin and the high fish oil diet showed the highest mortality rate and the lowest cardiac performance of all the experimental groups. CONCLUSIONS: Dietary fish oil may reduce antioxidant defences and accelerate susceptibility of the myocardium to lipid peroxidation in rats under doxorubicin treatment. This may partly explain why dietary fish oil does not prevent doxorubicin-induced cardiomyopathy.     

Role of 4-hydroxynonenal in modification of cytochrome c oxidase in ischemia/reperfused rat heart.

Mitochondrial dysfunction is a characteristic of ischemia/reperfusion (I/R) injury in the heart. While oxidative stress has been implicated in mitochondrial damage in I/R injury, the underlying mechanisms are unclear. 4-Hydroxynonenal (HNE) is a toxic aldehyde generated by lipid peroxidation. The purpose of the present study was to assess the role of HNE in I/R-induced damage of a crucial component of the mitochondrial electron transport chain, cytochrome c oxidase (COX). I/R was induced in male WKY rats by 15 mins of ischemia followed by reperfusion for up to 3 h. COX activity was measured spectrophotometrically at 550 nm. HNE adducts with COX subunits were detected by Western Blot using an HNE-histidine antibody. HNE and reduced glutathione (GSH) contents were measured in mitochondria by HPLC. Following 3 h of reperfusion, COX activity was reduced to 59% of control, accompanied by increases in HNE adducts with COX (P<0.05). Mitochondrial HNE content in reperfused hearts was increased to 165% of control, whereas GSH was decreased to 62% of control (P<0.05). After purified COX was incubated with HNE in vitro, COX activity was decreased progressively with increasing concentrations of HNE, accompanied by concentration-dependent formation of HNE adducts with COX. GSH prevented HNE adduct formation as well as COX inhibition by HNE. These results suggest that HNE, via adduct formation with COX subunits, plays an important role in COX dysfunction caused by reperfusion. The findings also indicate that decreases in mitochondrial GSH stores in reperfused myocardium could potentiate HNE-mediated COX damage.     

低硒环境下蛋氨酸对大鼠体内维生素E,硒及脂质过氧化物含量的影响

用低硒、低蛋氨酸饲料喂养大鼠8周后发现大鼠血清、肝脏及心肌中脂质过氧化物含量显著升高,血清维生素E显著下降,而心肌硒含量却显著升高。实验结果表明,在低硒环境下如降低饲料中蛋氨酸水平将导致大鼠体内脂质过氧化反应加剧。     

Effect of aminoguanidine on lipid peroxidation in streptozotocin-induced diabetic rats.

Diabetes mellitus is postulated to be associated with increased lipid peroxidation, which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine (AMGN), the prototype inhibitor of advanced glycosylation end product (AGE) formation, has been recently shown to prevent oxidative modification of low-density lipoprotein (LDL) in vitro at a moderate concentration. It is unknown whether AMGN may act as an antioxidant against lipid peroxidation under hyperglycemia in vivo. To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN (1 g/L in drinking water) or vitamin E (400 mg/d for 5 d/wk) to streptozotocin (STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II (FOX method) and red blood cell (RBC) membrane malondialdehyde (MDA) and related aldehydes as thiobarbituric acid-reactive substances (TBARS). Plasma lipid hydroperoxide was higher in STZ-induced diabetic rats versus control rats (mean +/- SD, 7.53 +/- 2.03 v 5.62 +/- 0.44 micromol/L, P < .05; n = 8 to 14). RBC membrane TBARS were also higher in STZ-induced diabetic rats than in control rats (2.67 +/- 0.46 v 1.81 +/- 0.19 nmol/mL, P < .05). Plasma lipid hydroperoxide was lower in AMGN-treated (6.23 +/- 0.59 micromol/L, P < .05) and vitamin E-treated (5.29 +/- 0.27 micromol/L, P < .05) diabetic rats than in untreated diabetic rats. RBC membrane TBARS were also lower in AMGN-treated (1.93 +/- 0.12 nmol/mL, P < .05) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, cholesterol, and triglyceride levels among diabetic groups. Although the mechanism(s) of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN may have an additional beneficial effect as an antioxidant against lipid peroxidation in a prevention trial for diabetic vascular complications.     

Inhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal and other lipid peroxidation products

Lipid peroxidation due to oxidative stress is accelerated under hyperglycemic conditions such as diabetes mellitus. The effect of 4-hydroxy-2-nonenal (HNE) and other lipid peroxidation products on the ability of isolated rat pancreatic islets to secrete insulin was examined in this study. HNE concentration- and time-dependently deteriorated glucose-induced insulin secretion: insulin secretion was decreased by 50% when measured after incubation of islets with 100 microM HNE for 1 h. Other lipid peroxidation products, e.g. 2-hexenal and 2-butenal, also inhibited glucose-induced insulin secretion. HNE at 100 microM lowered alpha-ketoisocaproate-induced insulin secretion, whereas leucine-induced insulin secretion was stimulated. Insulin secretion induced by 10 mM glyceraldehyde was slightly decreased by HNE. On the other hand, HNE severely decreased insulin secretion induced by 10 mM glyceraldehyde and 2.8 mM glucose. Glucose utilization and glucose oxidation were significantly lowered in islets treated with HNE. The amounts of fructose 1,6-bisphosphate and dihydroxyacetone phosphate in islets were decreased by treatment with HNE, whereas the amount of fructose 6-phosphate was increased. Our study indicates that HNE and other lipid peroxidation products impair insulin secretion induced by glucose probably through affecting both the glycolytic pathway and the citric acid cycle.