The effect of carnosine treatment on prooxidant–antioxidant balance in liver,heart and brain tissues of male aged rats

Carnosine (β-alanyl-l-histidine) is a dipeptide with antioxidant properties. Oxidative damage by free radicals is one of the mechanisms underlying the aging process. This study was done to investigate the effects of carnosine treatment on lipid peroxidation and antioxidant status of liver, heart, brain in male young and aged rats. At the initiation of study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to rats. At the end of this period, malondialdehyde (MDA) and diene conjugate (DC) and protein carbonyl (PC) levels, glutathione (GSH), vitamin E and vitamin C levels and Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined in tissues of carnosine-treated young and old rats. Liver and heart, but not brain MDA and DC levels increased significantly in aged rats as compared to young rats. Liver PC levels were also significantly elevated. Significant decreases in GSH and vitamin C levels and SOD activities were detected in liver of aged rats, but vitamin E levels and GSH-Px and GST activities remained unchanged. Non-enzymatic and enzymatic antioxidants did not change in heart and brain of aged rats. Carnosine treatment decreased high MDA, DC and PC levels and caused significant increases in vitamin E level and SOD activity in the liver of aged rats. There were no changes in non-enzymatic and enzymatic antioxidants in the heart and brain of carnosine-treated aged rats. In conclusion, carnosine treatment was found to be useful in the decrease of age-related oxidative stress in the liver.     

Impairment of Intestinal Mucosal Antioxidant Defense System During Salmonella typhimurium Infection

The mucosal pathology of Salmonella typhimuriuminfection may in part be due to the excessive productionof reactive oxygen species (ROS). The influence of S.typhimurium infection on the intestinal mucosal antioxidant defense system was investigated. Weinjected ligated rat ileal loops with Salmonella liveculture or toxin. After 18 hr of infection, the animalswere killed and enterocytes isolated from the ileal loops. The enterocyte-reduced glutathione(GSH) content and activities of the enzymes superoxidedismutase (SOD), glutathione peroxidase (GSH-Px),catalase, glutathione-S-transferase (GST), glutathione reductase (GR), and glucose-6-phosphatedehydrogenase (G6PDH) were spectrophotometricallyestimated. The vitamin E and A contents were determinedby high-performance liquid chromatography (HPLC). Inboth the Salmonella live culture and toxin-treatedgroups, the enterocyte GSH and vitamin E contents andactivities of the enzymes SOD, GSH-Px, catalase, GR, andG6PDH were significantly decreased as compared to the control group. However there was asignificant increase in the enterocyte activity of GST.There was no change in the vitamin A content of theenterocytes. These findings might indicate a decreased endogenous intestinal protection against ROS inS. typhimurium-mediated infection, which couldcontribute to the pathogenesis of the disease.     

Cordycepin (3′-deoxyadenosine) attenuates age-related oxidative stress and ameliorates antioxidant capacity in rats

Free radical-induced oxidative damage is considered to be the most important consequence of the aging process. The activities and capacities of antioxidant systems of cells decline with increased age, leading to the gradual loss of pro-oxidant/antioxidant balance and resulting in increased oxidative stress. Our investigation was focused on the effects of cordycepin (3′-deoxyadenosine) on lipid peroxidation and antioxidation in aged rats. Age-associated decline in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH), vitamin C and vitamin E, and elevated levels of malondialdehyde (MDA) were observed in the liver, kidneys, heart and lungs of aged rats, when compared to young rats. Furthermore, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine were found to be significantly elevated in aged rats compared to young rats. Aged rats receiving cordycepin treatment show increased activity of SOD, CAT, GPx, GR and GST, and elevated levels of GSH, and vitamins C and E such that the values of most of these parameters did not differ significantly from those found in young rats. In addition, the levels of MDA, AST, ALT, urea and creatinine became reduced upon administration of cordycepin to aged rats. These results suggest that cordycepin is effective for restoring antioxidant status and decreasing lipid peroxidation in aged rats.     

Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: Modulation by melatonin

Oxidative stress is an important factor for aging. The antioxidative enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and superoxide dismutase (SOD) play a crucial role protecting the organism against the age-dependent oxidative stress. Glutathione (GSH) is present in nearly all living cells. GSH is one of the main antioxidants in the cell and it serves several physiological functions. Our purpose was to evaluate the age-related changes in mitochondrial GPx, GRd and SOD activities, and mitochondrial GSH pool in the brains of young (3months) and aged rats (24months). We also investigated whether melatonin administration influences these brain mitochondrial enzyme activities and GSH levels in young and aged rats. The results showed that GPx activity increased with age, whereas melatonin treatment decreased GPx activity in the aged rats at levels similar to those in young and young+melatonin groups. The activities of GRd and SOD, however, did not change with age. But, melatonin treatment increased SOD activity in the aged rats. GSH levels, which also increased with age, were not modified by melatonin treatment. The reduction in the SOD/GPx and GR/GPx ratios with age was prevented by melatonin administration. Together, our results suggest that the age-related oxidative stress in rat brain mitochondria is more apparent when the antioxidant enzyme ratios are analyzed instead of their absolute values. The antioxidative effects of melatonin were also supported by the recovery of the enzyme ratios during aging.     

维生素E对小鼠慢性乙醇性肝损害的保护作用

目的 探讨乙醇性肝损害的发病机制，并研究维生素E对乙醇性肝损害的保护作用。方法 昆明种小鼠30只，分为三组：正常对照组（自由饮水，不做其他处理）、乙醇组（自由饮用2．5％乙醇8周）、乙醇＋维生素E组（自由饮用2．5％乙醇8周，同时经口给予维生素E200mg/kg，每天1次，共8周）。分别测定血清丙氨酸转氨酶、肝匀浆蛋白含量、肝匀浆丙二酰乙醛含量及肝匀浆超氧化物歧化酶、过氧化氢酶、谷胱甘肽、谷胱甘肽－S－转移酶、谷胱甘肽还原酶、谷胱甘肽过氧化酶的活性。结果 摄入乙醇8周后多种抗氧化酶及抗氧化物发生改变，维生素E可拮抗乙醇的上述作用，使指标的改变发生逆转。结论 维生素E对慢性乙醇性肝损害的保护作用。     

Protective function of alpha-tocopherol against the process of cataractogenesis in humans

In a random trial 50 patients with unilateral/ bilateral idiopathic immature senile cataract (cortical n = 25, nuclear n = 25) requiring surgery at least in one eye were included in the present study. Reduced glutathione (GSH), vitamin E, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were studied in these patients receiving either vitamin E (n = 12 in each subgroup) or placebo (n = 13 in each group) for 30 days. A comparable increase of vitamin E in both types of lens homogenates of cataractous patients was observed in the study group. The level of GSH in cortical cataractous lenses in the study group was significantly raised (p < 0.001) whereas it was not increased significantly in nuclear cataractous lenses (p > 0.05) as compared to the placebo group. The percentage decrease in MDA levels was greater in cortical cataracts (38.07%) than in the nuclear type (27.94%). The activity of GSH-Px in cortical lenses was higher than that in the nuclear cataractous lens. The change in the size of lens opacity in cortical cataractous patients receiving vitamin E therapy was significantly decreased as compared to the placebo group. There may be a direct modulating effect of vitamin E on some GSH-related enzymes and the cortex of the lens might be protected more than the nucleus.     

Antioxidant therapy and streptozotocin-induced diabetes in pregnant rats

The aim of our study was to analyse the effect of chronic hyperglycaemia on lipid peroxidation and scavenging enzyme activity in pregnant animals and their offspring supplemented and not supplemented with vitamin E – a natural antioxidant. Thirty pregnant female Wistar rats were used in our experiments. Diabetes was induced on day 7 of pregnancy using a single does of streptozotocin (40 mg/kg). Diabetic animals were divided into two equal groups: vitamin E supplemented and those fed with standard diet. Our controls consisted of 15 healthy rats. On day 1 after delivery homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn superoxide dismutase (SOD) and glutathione peroxidase (GPx) (Bioxytech, France). Statistical analysis was performed using Mann-Withney U test. The neonates of diabetic rats were smaller than those from healthy rats and serum glucose concentration was markedly higher in diabetic animals, both in mothers and neonates. MDA levels increased significantly, whereas GSH content and SOD as well as GPx activities were markedly diminished in diabetic pregnant rats and their offspring in comparison with the control group. In animals supplemented with tocopherol, MDA concentrations declined significantly, GSH contents and SOD activities were markedly elevated in almost all types of tissues studied, whereas glutathione peroxidase remained suppressed. Our results suggest that diabetic pregnant rats and their neonates are exposed to oxidative stress (OS), but vitamin E supplementation could in part reduce the imbalance between uncontrolled reactive oxygen species generation and scavenging enzyme activity, and may potentially serve as a useful prophylactic factor against OS development: Received: 4 January 1999 / Accepted in revised form: 19 May 1999     

Protective effect of melatonin on random pattern skin flap necrosis in pinealectomized rat

Random pattern skin flaps are still widely used in plastic surgery. However, necrosis in the distal portion resulting from ischemia is a serious problem, increasing the cost of treatment and hospitalization. Free oxygen radicals and increased neutrophil accumulation play an important role in tissue injury and may lead to partial or complete flap necrosis. To enhance skin flap viability, a variety of pharmacological agents have been intensively investigated. The aim of this study is to test the effects of melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant, on random pattern skin flap survival in rats. Herein, to investigate the physiological and pharmacological role of melatonin on dorsal skin flap survival. Pharmacological (0.4, 4 and 40 mg/kg) levels of melatonin were given intraperitoneally (i.p.). For this, pinealectomized (Px) and sham operated (non-Px) rats were used. The effects of melatonin on levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were measured in the skin flap. The ratio of skin flap necrosis was compared among the experimental groups by using planimetry. MDA and NO levels were found to be higher in Px than non-Px rats; while GSH levels and GSH-Px, and SOD activities were reduced. Melatonin administration to Px rats reduced MDA and NO levels and increased GSH, GSH-Px, SOD levels. Melatonin also reduced the ratio of flap necrosis determined by using planimetry and supported through the photography. In conclusion, these results show that both physiological and pharmacological concentrations of melatonin improve skin flap viability.     

Cyclophosphamide-induced depression of the antioxidant defense mechanisms of the lung

Cyclophosphamide causes lung toxicity in a wide variety of animals, including humans. Recent evidence suggests that oxygen (O2) potentiates cyclophosphamide-induced pulmonary injury. We hypothesized that cyclophosphamide or one of its toxic metabolites, acrolein, may potentiate O2 toxicity by depressing lung antioxidant defense mechanisms. To test this, we gave rats cyclophosphamide (100 mg/kg), acrolein (5 mg/kg), or a vehicle (control) in a single intraperitoneal injection and then killed them during a 5-day study period. Excised lungs were analyzed for reduced glutathione (GSH) content, glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSH-R), glutathione peroxidase (GSH-P), and superoxide dismutase (SOD) activities. In the lungs of cyclophosphamide-treated rats, GSH content was increased 48% (P less than 0.001) on day 2 but progressively decreased to 50% of control values (P less than 0.001) on day 5. Significant reductions (P less than 0.005) in G6PD, GSH-R, and GSH-P activities occurred on days 1-5, and SOD activity was significantly decreased (P less than 0.005) on days 4 and 5 by cyclophosphamide. In acrolein-treated rats, GSH content and GSH-R, GSH-P, and SOD activities were indistinguishable from those in controls. However, G6PD was increased (35-38%) on days 2 and 3 but returned to control values thereafter. To assess whether the cyclophosphamide-induced reduction in lung antioxidant defenses increased susceptibility to acute O2 toxicity, we gave a separate group of rats cyclophosphamide, acrolein, or vehicle, and 4 days later exposed them to 100% O2 or air at 1 atmosphere absolute. All cyclophosphamide-, acrolein-, and vehicle-treated rats survived 60 h air exposure, and all vehicle-treated rats exposed to 100% O2 survived. In contrast, all of the cyclophosphamide-treated rats exposed to 100% O2 died (P less than 0.05) within 40 h. Acrolein had no effect on survival in 100% O2. These results indicate that cyclophosphamide, but not acrolein, depresses lung antioxidant defense mechanisms, which may be responsible for increased mortality from O2 toxicity in cyclophosphamide-treated animals.     

Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model

D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5 % w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.     

Effect of fermented Panax ginseng extract (GINST) on oxidative stress and antioxidant activities in major organs of aged rats

The intracellular levels of oxidant and antioxidant balances are gradually distorted during the aging process. An age associated elevation of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The present study was undertaken to evaluate the putative antioxidant activity of the fermented Panax ginseng extract (GINST) on lipid peroxidation and antioxidant status of major organs of aged rats compared to young rats. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were observed in the serum of aged rats. Increased levels of malondialdehyde (MDA) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were observed in the liver, kidneys, heart and lungs of aged rats, when compared with those in young rats. Quantitative analysis of the non-enzymatic antioxidants such as reduced glutathione (GSH), ascorbic acid and α-tocopherol levels showed significantly lower values in the liver, kidneys, heart and lungs of aged rats. On the other hand, administration of the fermented Panax ginseng extract (GINST) to aged rats resulted in increased activities of SOD, CAT, GPx, GR and GST as well as elevation in GSH, ascorbic acid and α-tocopherol levels. Besides, the level of MDA, AST, ALT, urea and creatinine were reduced on administration of GINST to aged rats. These results suggested that treatment of GINST can improve the antioxidant status during aging, thereby minimizing the oxidative stress and occurrence of age-related disorders associated with free radicals.     

Glutathione metabolism enzymes in brain and liver of hyperphenylalaninemic rats and the effect of lipoic acid treatment

Phenylketonuria (PKU) is a disorder caused by a deficiency in phenylalanine hydroxylase activity, which converts phenylalanine (Phe) to tyrosine, leading to hyperphenylalaninemia (HPA) with accumulation of Phe in tissues of patients. The neuropathophysiology mechanism of disease remains unknown. However, recently the involvement of oxidative stress with decreased glutathione levels in PKU has been reported. Intracellular glutathione (GSH) levels may be maintained by the antioxidant action of lipoic acid (LA). The aim of this study was to evaluate the activity of the enzymes involved in the metabolism and function of GSH, such as glutathione peroxidase (GSH-Px), glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GR), glutamate-cysteine ligase (GCL), glutathione-S-transferase (GST) and GSH content in brain and liver of young rats subjected to a chemically induced model of HPA and the effect of LA for a week. In brain, the administration of Phe reduced the activity of the GSH-Px, GR and G6PD and LA prevented these effects totally or partially. GCL activity was increased by HPA and was not affect by LA antioxidant treatment. GST activity did not differ between groups. GSH content was increased by LA and decreased by HPA treatment in brain samples. Considering the liver, all parameters analyzed were increased in studied HPA animals and LA was able to hinder some effects except for the GCL, GST enzymes and GSH content. These results suggested that HPA model alter the metabolism of GSH in rat brain and liver, which may have an important role in the maintenance of GSH function in PKU although liver is not a directly affected organ in this disease. So, an antioxidant therapy with LA may be useful in the treatment of oxidative stress in HPA.     

Antioxidant Protection Systems of Rat Lung after Chronic Ethanol Inhalation

The effect of chronic ethanol administration on pulmonary antioxidant protection systems was investigated in male Sprague-Dawley rats exposed to room air or room air containing ethanol vapors for 5 weeks. Blood ethanol concentrations in ethanol-exposed rats were usually between 200 and 300 mg/dl. Glutathione, vitamin E, and malondialdehyde concentrations were measured in lung homogenates, and antioxidant enzyme activities (catalase, glutathione peroxidase, Cu/Zn-superoxide dismutase, glutathione reductase) were determined in the supernatant fractions. For comparison, the measurements were also made using liver fractions. Ethanol treatment increased the activities of catalase (117%) and Cu/Zn-superoxide dismutase (25%) in lung but not in liver. Although chronic ethanol inhalation lowered hepatic glutathione (19%) and hepatic vitamin E (33%), there was no increase in malondialdehyde content in either liver or lung of ethanol-exposed rats. The elevation of pulmonary antioxidant enzyme activities could be interpreted to mean that lung is a target for ethanol-induced oxidative stress. However, as there was no loss of pulmonary GSH or vitamin E and no increase in malondialdehyde formation, it appears that long-term ethanol exposure did not produce a significant degree of oxidative stress in rat lung.     

Changes in the transmural distribution of antioxidant enzyme activities across the left ventricle heart wall from rats fed ad libitum or food-restricted during growth and aging

Data on vulnerability to injury and on the larger age-related accumulation of lipofuscin in the subendocardial myocardium prompted us to investigate the changes in the levels and in the transmural distribution of catalase (C), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities across the left ventricle heart wall of rats fed ad libitum a standard diet or submitted to intermittent feeding during growth and aging. Enzyme activities were assayed by standard techniques on subepicardial, midmyocardial or subendo- cardial tissue obtained by cutting the heart wall into 100-microm-thick sections at the cryostat. The levels of GSH-Px and of C (but not of SOD) activity increased with age and reached their highest values in the subendocardial region by adulthood or senescence, respectively. No effect was observed of intermittent feeding on age-related changes in enzyme levels and transmural distribution.     

Prevention by melatonin of hepatocarcinogenesis in rats injected with N-nitrosodiethylamine

N-nitrosodiethylamine (NDEA) is a potent carcinogenic agent that induces liver cancer. To evaluate the chemopreventive function of melatonin in this experimental model, Wistar male rats received a single i.p. injection of NDEA or vehicle followed by weekly s.c. injections of carbon tetrachloride or vehicle for 6 weeks. Melatonin (5 mg/kg body weight) or its vehicle (0.5 mL saline) was given i.p. on a daily basis 2 hr before lights off for 20 wk. At the end of this period the rats were killed and liver and blood samples were taken for histological and biochemical studies. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein were measured in serum. To assess lipid peroxidation and the antioxidant status in liver and blood, the levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was assessed in liver and erythrocyte fraction of NDEA-treated rats. NDEA administration inhibited body weight, macro- and microscopically detectable liver tumors and increased levels of plasma AST, ALT and alpha-fetoprotein. NDEA treatment decreased liver TBARS levels and CAT and SOD activities and increased liver GSH levels and GST and GPx activities. Plasma TBARS were augmented, while plasma GSH levels and the activities of erythrocyte CAT, SOD, GST and GPx decreased, in NDEA-treated rats. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects.     

Malanga (Xanthosoma sagittifolium) and purslane (Portulaca oleracea) leaves reduce oxidative stress in vitamin A-deficient rats

AIM: This study examined the ability of tropical vegetables to reduce oxidative stress induced by vitamin A deficiency. METHODS: Vitamin A-deficient male Wistar rats were divided into four groups which were treated for 30 days with different diets: AIN-93G vitamin A-deficient diet (DD), DD supplemented with pure beta-carotene (beta-D) and DD supplemented with malanga (Xanthosoma sagittifolium) (MD) or purslane (Portulaca oleracea) (PD) leaves as the only source of vitamin A. The thiobarbituric acid-reactive substances (TBARS), reduced (GSH) and oxidized (GSSG) glutathione, and antioxidant enzyme activities were determined in the heart and liver. RESULTS: The rats fed beta-D, MDand PD showed liver and heart TBARS concentrations lower than did DD rats. The liver GSH concentration of beta-D, MD and PD rats was lower compared to DD rats. The heart GSSG concentration of the vegetable groups was significantly lower than in DD rats. Liver and heart catalase activities were not significantly different among the groups, nor was heart glutathione peroxidase (GPX) activity, however the beta-D rats showed the highest liver GPX activity. There was no difference in liver glutathione-S-transferase level among the groups, while heart activity was higher in rats fed the vegetable leaves. CONCLUSION: This study evidences that the ingestion of purslane or malanga leaves may have a protective effect against oxidative stress caused by vitamin A deficiency.     

Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats

Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats each [control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (P<0.001 and P<0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ-induced experimental diabetes and indicate the beneficial free radical-scavenging and antioxidant properties of melatonin.     

抗氧化剂对去卵巢大鼠骨密度和血清生化指标的影响

目的 研究抗氧化剂维生素C、E及还原型谷胱甘肽(GSH)不同配伍用药方法对去卵巢大鼠骨密度及血清生化指标的影响.方法 4月龄雌性SD大鼠70只,随机取50只行双侧卵巢切除术,20只行假手术.3个月后随机从手术组和假手术组各取10只大鼠检测体重、子宫湿重、左侧股骨及腰椎骨密度和血清生化指标Ca2+、肌酐、碱性磷酸酶(ALP)水平,以确定骨质疏松模型建立成功.确定模型建立成功后,其余动物分为A(假手术)、B(去卵巢生理盐水对照组)、C(维生素C+维生素E)、D(GSH)、E(维生素C+维生素E十GSH)5组,每组10只.药物用最维牛素C(750 mg·kg-1·d-1)、GSH(125 mg·kg-1·d-1)腹腔注射,维牛素E(250 mg·kg-1·d-1)灌胃,模型组每天以生理盐水腹腔注射.3个月后,检测各组动物左侧股骨及腰椎骨密度和血清生化指标.结果 抗氧化剂治疗3个月后,与模型组相比,左侧股骨及腰椎骨密度三个治疗组均明显增加,其中D、E组增加最显著;血清ALP各组均显著降低;超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平和血清抑制OH-能力D、E组显著升高;丙二醛水平C、D组显著降低;各组血清Ca2+水平无明显改变.结论 抗氧化剂维生素C、维生素E及GSH显著增加去卵巢骨质疏松模型大鼠骨密度,阻止血清抗氧化成分(SOD、GSH-Px)减少,提高血清抑制OH-能力,降低脂质过氧化物丙二醛.     

Lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes

The aim of this study was to evaluate lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes, and then to establish whether moderate doses of nonenzymatic antioxidant vitamin E play a role in the antioxidant defence system in diabetic pregnant rats and their offspring. The study group consisted of 30 normal female Wistar rats, which were given a single dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the diabetic animals were divided into two matched groups: the first supplemented with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking vitamine E. Controls consisted of 15 pregnant rats. On the first day after delivery, the rats were decapitated and homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats were smaller than the healthy ones and serum glucose concentration was markedly higher in the diabetic animals. MDA levels were significantly increased, whereas GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their offspring in comparison to the control grouop. In the animals supplemented with α-tocopherol, MDA concentrations were significantly lower, GSH content and SOD activities were markedly elevated most tissues studied, whereas GPx remained unchanged. We conclude that, by monitoring the activity of selected scavenging enzymes, information on ongoing biological oxidative stress and thereby on the fetus/neonate status may be obtained. Our results suggest that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects. Received: 20 January 2000 / Accepted in revised form: 23 February 2001     

Glucose-6-phosphate dehydrogenase activity in dorsal root ganglia of vitamin E-deficient rats

The effect of dietary vitamin E on the activity of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) was studied in the dorsal root ganglia of rat. One-month-old male Sprague-Dawley rats were randomly assigned to two dietary treatment groups for 2 months. The first received a standard diet supplemented with vitamin E, the second was fed a basal vitamin E-deficient diet. The activity of G6PD was markedly decreased in ganglia of the deficient animals with respect to the controls. On the other hand, the activity of the 6PGD was not significantly altered in the deficient animals. In the red cells the two enzyme activities presented a similar situation and the level of the reduced glutathione in the red cells was not significantly altered by the status of dietary vitamin E. Kinetic analysis with crude extracts of ganglia or partially purified G6PD demonstrated that there was no direct modulatory effect of the vitamin on the enzyme activity. Moreover, nondenaturing gel electrophoresis performed in this study revealed that none of the three G6PD activity bands which appeared on the acrylamide gel were significantly altered in the deficient animals. At present, the mechanism linking the G6PD activity with the status of dietary vitamin E remains unknown. Our results suggest, however, that a reduced NADPH generation produced by a decay of G6PD activity may limit the glutathione peroxidase, a very active enzyme in detoxifying peroxides, and may predispose the nervous tissue to oxidant injury.