The effect of lipoic acid on antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress

This study was designed to investigate effect of alpha-lipoic acid (LA) on lipid peroxidation, nitric oxide production and antioxidant systems in rats exposed to chronic restraint stress. Twenty four male Wistar rats, aged three months, were divided into four groups: control (C), the group treated with LA (L), the group exposed to restraint stress (S) and the group exposed to stress and treated with LA (LS). Restraint stress was applied for 21 days (1 h/day) and LA (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Restraint stress significantly decreased brain copper/zinc superoxide dismutase (Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared with the control group. Thiobarbituric acid reactive substances (TBARS), nitrite and nitrate levels were significantly increased in the tissues of the S group compared with the C group. LA produced a significant decrease in brain and retina TBARS, nitrite and nitrate levels of the L and LS groups compared to their corresponding control groups. LA increased all enzyme activities in the tissues of the LS group compared to the S group. Our study indicated that LA is an ideal antioxidant candidate for the prevention of stress-induced lipid peroxidation.     

慢性束缚应激对SD和Wistar大鼠学习记忆能力的影响

目的探讨慢性束缚应激对Wistar、SD两种品系大鼠学习记忆能力的影响,为应激模型中实验动物的选择提供依据。方法对两种品系大鼠(Wistar、SD)采用每天束缚10 h,束缚28 d建立慢性应激模型。采用物体认知新物体识别实验和Morris水迷宫空间学习、工作记忆行为学检测方法,观察束缚应激对两种品系实验动物学习记忆能力的影响。结果束缚28 d后,物体识别实验中,Wistar、SD模型组的辨别指数(discrimination index,DI)均低于对照组,但只有SD两组间差异存在显著性(P0.05);水迷宫空间学习阶段,SD模型组潜伏期高于对照组,第5天差异有显著性(P0.05),而Wistar模型组与对照组间的潜伏期没有差异;水迷宫工作记忆阶段,SD大鼠模型组与正常组比较,潜伏期显著增加(P0.05),Wistar模型大鼠的潜伏期与对照组比较没有显著差异。结论新物体识别实验和水迷宫实验,这两种反应动物不同学习记忆能力的行为学实验结果都表明,慢性束缚应激(10 h,28 d)对SD大鼠学习记忆能力的损伤较Wistar大鼠明显。SD大鼠可能更适合作为慢性应激所致学习记忆损伤动物模型。     

Preventive effects of omega-3 and omega-6 Fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells

Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H₂O₂, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H₂O₂ further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H₂O₂ stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H₂O₂ mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H₂O₂ induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease.     

Acute and chronic restraint stress alter the incidence of social conflict in male rats

Stress and elevated stress hormone levels are known to alter cognition, learning, memory, and emotional responses. Three weeks of chronic stress or glucocorticoid exposure is reported to alter neuronal morphology in the hippocampus, the amygdala, and the prefrontal cortex, and to decrease neurogenesis in the dentate gyrus. Here we examine the effects of acute and chronic restraint stress exposure on the incidence of emotional responses throughout a 3-week period among adult rat conspecifics. Our data indicate that acute restraint stress (i.e., a single 6-h exposure) results in a significant reduction in aggressive conflicts among stressed males compared to experimental controls. In contrast, on Days 14 and 21, repeatedly restrained rats exhibited significantly more aggressive behaviors than controls. Blood samples taken 18 h after the last restraint session indicate that plasma concentrations of the stress hormone corticosterone (CORT) in stressed rats were equivalent to those of unstressed rats; however, the number of individually initiated aggressive acts observed positively correlated with plasma CORT measures taken at the end of the study. In contrast to studies of psychosocial stress or intruder paradigms, here we observe spontaneous emotional responses to an uncontrollable stressor in the homecage. This study provides a novel examination of the effects of chronic restraint stress on emotional responses in the home environment among cagemates. These results indicate that acute and chronic restraint stress alter the incidence of aggression, and emphasize the relevance of this model of chronic stress to studies of stress-responsive disorders characterized by aggressive behavior.     

Repeated handling, restraint, or chronic crowding impair the hypothalamic-pituitary-adrenocortical response to acute restraint stress.

The purpose of the present study was to assess whether, and to what extent prior handling, restraint or social crowding stress during 3-10 days affects the hypothalamic-pituitary-adrenocortical (HPA) response to an acute short-lasting restraint stress. Also the effect of a feedback inhibitory mechanism of corticosterone in the impairment of HPA axis by these stressors was investigated. Male Wistar rats were pretreated with handling 1 min/day for 3-10 days, restraint 2 times daily for 3-7 days and crowding stress for 7 days before exposure to acute restraint stress in metal tubes for 10 min. Some group of rats received exogenous s.c. corticosterone either once 25 mg/kg or 2 times daily 10 mg/kg for 3-10 days before restraint stress. After the last restraint the rats were decapitated and their trunk blood was collected for the measurement of plasma ACTH and serum corticosterone levels. Handling for 3-7 days, restraint for 3-7 days, and crowding for 7 days and a single pretreatment with corticosterone--all significantly and to a similar extent inhibited the restraint stress-induced increase in ACTH and corticosterone secretion. Chronic pretreatment with corticosterone blunted the restraint stress-induced increase in HPA axis activity. These results indicate that repeated short-lasting stress induced by handling, restraint, or crowding potently attenuates the acute restraint stress-induced stimulatory action of the HPA axis. They also indicate adaptive action of moderate stress on the HPA axis response to acute stress. The results also suggest that a short-lasting hypersecretion of corticosterone during psychological stress may induce a prolonged feedback inhibition of the HPA axis activity. The attenuation of HPA axis response by prior handling has also obvious methodological implications.     

DS-1226对慢性限制活动大鼠的抗抑郁作用

目的研究人参皂苷水解脱糖产物DS-1226对慢性限制活动大鼠的抗抑郁作用,为抗抑郁药物的研发提供实验数据。方法将90只雄性Sprague-Dawley大鼠随机分为6组,每组15只,分别为对照组（control）、模型组（model）、西酞普兰组（citalopram,100 mg/kg）、低剂量组（DS-1226,18.75 mg/kg）、中剂量组（DS-1226,37.5mg/kg）、高剂量组（DS-1226,75 mg/kg）。预防7 d给药后进行每天14 h连续28 d的限制活动造模并连续给药。造模过程中每周监测体重并在造模完成后进行糖水偏爱、新奇事物、自主活动实验,测试完成后处死动物取血清检测皮质酮含量。结果经过慢性限制活动应激后,模型组大鼠的体重和糖水偏爱指数降低,对新奇事物的探索行为以及自主活动尤其是中央区的活动减少,血中的皮质酮含量升高。但中剂量、高剂量的DS-1226和西酞普兰能不同程度的提高慢性限制活动大鼠的体重和糖水偏爱指数,增加对新奇事物的探索次数、探索时间、降低潜伏期时间,增加自主活动尤其是中央区的活动,降低血中皮质酮的含量。结论 DS-1226具有改善慢性限制活动大鼠抑郁行为的作用。     

Fatty acid-related phylogeny of myxobacteria as an approach to discover polyunsaturated omega-3/6 Fatty acids

In an analysis of 47 aerobic myxobacterial strains, representing 19 genera in suborders Cystobacterineae, Nannocystineae, Sorangiineae, and a novel isolate, "Aetherobacter" SBSr008, an enormously diverse array of fatty acids (FAs) was found. The distribution of straight-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) supports the reported clustering of strains in the phylogenetic tree based on 16S rRNA genes. This finding additionally allows the prediction and assignment of the novel isolate SBSr008 into its corresponding taxon. Sorangiineae predominantly contains larger amounts of SCFA (57 to 84%) than BCFA. On the other hand, Cystobacterineae exhibit significant BCFA content (53 to 90%), with the exception of the genus Stigmatella. In Nannocystineae, the ratio of BCFA and SCFA seems dependent on the taxonomic clade. Myxobacteria could also be identified and classified by using their specific and predominant FAs as biomarkers. Nannocystineae is remarkably unique among the suborders for its absence of hydroxy FAs. After the identification of arachidonic (AA) FA in Phaselicystidaceae, eight additional polyunsaturated fatty acids (PUFAs) belonging to the omega-6 and omega-3 families were discovered. Here we present a comprehensive report of FAs found in aerobic myxobacteria. Gliding bacteria belonging to Flexibacter and Herpetosiphon were chosen for comparative analysis to determine their FA profiles in relation to the myxobacteria.     

Endocrine and cardiovascular rhythms differentially adapt to chronic phase-delay shifts in rats

Disturbances in regular circadian oscillations can have negative effects on cardiovascular function, but epidemiological data are inconclusive and new data from animal experiments elucidating critical biological mechanisms are needed. To evaluate the consequences of chronic phase shifts of the light/dark (LD) cycle on hormonal and cardiovascular rhythms, two experiments were performed. In Experiment 1, male rats were exposed to either a regular 12:12 LD cycle (CONT) or rotating 8-h phase-delay shifts of LD every second day (SHIFT) for 10 weeks. During this period, blood pressure (BP) was monitored weekly, and daily rhythms of melatonin, corticosterone, leptin and testosterone were evaluated at the end of the experiment. In Experiment 2, female rats were exposed to the identical shifted LD schedule for 12 weeks, and daily rhythms of BP, heart rate (HR) and locomotor activity were recorded using telemetry. Preserved melatonin rhythms were found in the pineal gland, plasma, heart and kidney of SHIFT rats with damped amplitude in the plasma and heart, suggesting that the central oscillator can adapt to chronic phase-delay shifts. In contrast, daily rhythms of corticosterone, testosterone and leptin were eliminated in SHIFT rats. Exposure to phase shifts did not lead to increased body weight and elevated BP. However, a shifted LD schedule substantially decreased the amplitude and suppressed the circadian power of the daily rhythms of BP and HR, implying weakened circadian control of physiological and behavioural processes. The results demonstrate that endocrine and cardiovascular rhythms can differentially adapt to chronic phase-delay shifts, promoting internal desynchronization between central and peripheral oscillators, which in combination with other negative environmental stimuli may result in negative health effects.     

Physiological changes in rats exposed to cold/restraint stress.

An investigation was made into the effects of cold/restraint stress in rats on renal function, plasma constituents, blood count and endocrine function. Cold/restraint caused an increased volume of urine output, with increased K⁺ and urea excretion, and decreased Na⁺ and Cl^? excretion. There was a fall in plasma glucose, and a rise in plasma urea. A marked leucopenia was found, and the blood pH was significantly lowered. Cold/restraint was also found to cause marked increases in corticosterone and thyroxine levels, and a fall in the insulin level.     

Gender differences in oxidative stress in spinal cord of rats submitted to repeated restraint stress

Behavioral and neurochemical gender-specific effects have been observed following repeated stress. The aim of this study is to verify the effects of repeated restraint stress on free radical production (evaluated by DCF test), lipoperoxidation (evaluated by TBARS levels), and total antioxidant reactivity (TAR) in the spinal cord of male and female rats. Results demonstrate no effect on lipoperoxidation; chronic stress decreased TAR both in male and female spinal cord. In addition, gender differences were observed both in TAR and in the production of free radicals, both being increased in females. These results may be relevant to the gender-specific differences observed after exposure to repeated stress.     

Effects of restraint stress on catecholamine concentrations in the glandular stomach of rats

Restraint stress is known to induce gastric ulcers in rats. Peripheral sympathetic activity and catecholamines are involved in the pathogenesis of these gastric ulcers. The aim of the present study was to evaluate the effects of restraint on mucosal and muscle catecholamine concentrations in the glandular stomach of rats. In unrestrained rats, noradrenaline concentration was higher in the muscle than in the mucosa of the glandular stomach (629 +/- 106 vs 18 +/- 3 pg/mg and 217 +/- 37 vs 18 +/- 8 pg/mg, respectively in the corpus and the antrum, p less than 0.01). This can be explained by the existence of an abundant noradrenergic innervation in the muscle layer. After 20 hours of restraint, adrenaline and noradrenaline concentrations were significantly decreased in adrenals, in comparison with unrestrained animals (255 +/- 53 vs 638 +/- 160 ng/mg and 113 +/- 17 vs 198 +/- 37 ng/mg, respectively for adrenaline and noradrenaline, p less than 0.05). In the glandular stomach, noradrenaline and adrenaline concentrations in restrained rats were not significantly different from those in unrestrained rats. However, adrenaline concentrations in the muscle of restrained rats were higher than in the mucosa. Moreover, restraint induced a significant decrease in dopamine concentration in the antral mucosa (from 100 +/- 12 pg/mg in unrestrained rats to 15 +/- 5 pg/mg in restrained rats), suggesting that a depletion in dopamine in the antral mucosa could be one of the pathogenetic factors involved in antral gastric stress-induced ulcers in rats.     

Correlations between blood and tissue omega-3 LCPUFA status following dietary ALA intervention in rats

The aim of this study was to assess relationships between the fatty acid contents of plasma and erythrocyte phospholipids and those in liver, heart, brain, kidney and quadriceps muscle in rats. To obtain a wide range of tissue omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA) we subjected weanling rats to dietary treatment with the n-3 LCPUFA precursor, alpha linolenic acid (ALA, 18:3 n-3) for 3 weeks. With the exception of the brain, we found strong and consistent correlations between the total n-3 LCPUFA fatty acid content of both plasma and erythrocyte phospholipids with fatty acid levels in all tissues. The relationships between eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) content in both blood fractions with levels in liver, kidney, heart and quadriceps muscle phospholipids were stronger than those for docosahexaenoic acid (DHA, 22:6 n-3). The strong correlations between the EPA+DHA (the Omega-3 Index), total n-3 LCPUFA and total n-3 PUFA contents in both plasma and erythrocyte phospholipids and tissues investigated in this study suggest that, under a wide range of n-3 LCPUFA values, plasma and erythrocyte n-3 fatty acid content reflect not only dietary PUFA intakes but also accumulation of endogenously synthesised n-3 LCPUFA, and thus can be used as a reliable surrogate for assessing n-3 status in key peripheral tissues.     

Dissociation between adrenocorticotropin and corticosterone responses to restraint after previous chronic exposure to stress

The effect on emotional reactivity produced by a model for chronic stress in which different types of acute stresses were randomly combined for 29 days was studied in adult male rats. Chronically stressed rats showed a slight decrease in body weight gain and an increase in relative adrenal weight. Chronic stress did not modify defecation rate but reduced exploratory activity in the holeboard. Neither basal nor acute-stress induced levels of adrenocorticotropin (ACTH) were modified by previous chronic stress. Likewise, basal corticosterone levels were similar in both groups. However, corticosterone response to acute restraint stress was higher in chronically stressed than in control rats. The mechanisms underlying the dissociation between ACTH and corticosterone as well as its possible implications are discussed.     

Effects of venlafaxine on the expression level and methylation status of genes involved in oxidative stress in rats exposed to a chronic mild stress

Recent human and animal studies indicate that oxidative and nitrosative stress may play a role in the aetiology and pathogenesis of depression. This study investigates the effect of chronic administration of the serotonin-norepinephrine reuptake inhibitor, venlafaxine, on the expression and methylation status of SOD1, SOD2, GPx1, GPx4, CAT, NOS1 and NOS2 in the brain and blood of rats exposed to a chronic mild stress (CMS) model of depression. Separate groups of animals were exposed to CMS for 2 or 7 weeks; the second group received saline or venlafaxine (10 mg/kg/d, IP) for 5 weeks. After completion of both stress conditions and drug administration, the mRNA and protein expression of selected genes and the methylation status of their promoters were measured in peripheral mononuclear blood cells (PBMCs) and in brain structures (hippocampus, amygdala, hypothalamus, midbrain, cortex, basal ganglia) with the use of TaqMan Gene Expression Assay, Western blot and methylation-sensitive high-resolution melting techniques. CMS caused a decrease in sucrose consumption, and this effect was normalized by fluoxetine. In PBMCs, SOD1, SOD2 and NOS2 mRNA expression changed only after venlafaxine administration. In brain, CAT, Gpx1, Gpx4 and NOS1 gene expression changed following CMS or venlafaxine exposure, most prominently in the hippocampus, midbrain and basal ganglia. CMS increased the methylation of the Gpx1 promoter in PBMCs, the second Gpx4 promoter in midbrain and basal ganglia, and SOD1 and SOD2 in hippocampus. The CMS animals treated with venlafaxine displayed a significantly higher CAT level in midbrain and cerebral cortex. CMS caused an elevation of Gpx4 in the hippocampus, which was lowered in cerebral cortex by venlafaxine. The results indicate that CMS and venlafaxine administration affect the methylation of promoters of genes involved in oxidative and nitrosative stress. They also indicate that peripheral and central tissue differ in their response to stress or antidepressant treatments. It is possible that that apart from DNA methylation, a crucial role of expression level of genes may be played by other forms of epigenetic regulation, such as histone modification or microRNA interference. These findings provide strong evidence for thesis that analysis of the level of mRNA and protein expression as well as the status of promoter methylation can help in understanding the pathomechanisms of mental diseases, including depression, and the mechanisms of action of drugs effective in their therapy.     

The Influence of Fatty Acid Micelles on the Assays for Sod Activity

The influence of fatty acid (FA) micelles on cytochrome c(cyt.c) reduction and nitroblue tetrazolium (NBT) reduction assays for SOD activity, which continue to be widely used, has been studied. In the presence of FA micelles, the use of cyt.c reduction assay was found to overestimate the real activity of SOD. This effect is attributed to the following reasons. 1. The FA micelles lead to the denaturation of cyt.c, which gives rise to suppression of the reactivity of ferricyt.c (cyt.c(ox)) towards O₂^-. Furthermore, this denaturation increases the reoxidation rate of ferrocyt.c, and consequently the reoxidation causes a decreased rate of cyt.c(ox) reduction. 2. Positively charged cyt.c(ox) interacts with negatively charged FA micelles, and so cyt.c(ox) on the surface of FA micelles reacts less with negatively charged O₂^- because of electrostatic repulsion. Also in NBT reduction assay using a positively charged probe molecule, FA micelles cause the appearance of enhancement of SOD activity, due to suppression of the reactivity of NBT towards O₂^- by electrostatic repulsion. However, in both chemiluminescence assay using the uncharged probe molecule and LDH-N ADH assay using the negatively charged probe molecule, FA micelles cannot influence the assays of the SOD activity, because the micelles do not interact electrostatically with probe molecules.     

Accelerative effect of olive oil on liver glycogen synthesis in rats subjected to water-immersion restraint stress

The effects of dietary oils on stress-induced changes in the liver glycogen metabolism of male Wistar rats at 6 weeks of age were investigated. The rats were subjected to repetitive water-immersion restraint and fed with a 20% saturated fatty acid mixture (PSC), olive oil (OLI), safflower oil (SAF), or linseed oil (LIS) diet. Stress loading decresed the body weight gain, although the food intake was hardly changed, and the weights of the liver and spleen generally declined regardless of the elapsed time after stress loading and the type of dietary oil. The adrenal weight was generally enhanced by stress in all deitary groups, and particularly tended to be greater in the OLI and PSC groups than in the other two. The plasma corticosterone concentration increased immediately after stressing (Stress-1), but approached the level of the rats with no stress (No stress) 2 h after releasing the stress load (Stress-2) in all groups. The enhancement of corticosterone level in the Stress-1 animals was large in the PSC and OLI groups, and the decline of this level in the Stress-2 animals was small in the OLI group when compared with the other groups. Although the concentrations of total cholesterol (T-CHOL) and triacylglycerol (TG) in the plasma were decreased by stress loading in all groups, these concentrations in the PSC and OLI groups were nearly always higher than in the other groups. The liver serine dehydratase (SDH) activity enhanced by stress was high in the OLI group and tended to be high in the PSC group when compared with the other groups. The contents of liver glycogen were reduced in the Stress-1 animals and extremely elevated in the Stress-2 animals of all groups, and particularly in the OLI group, the reduction in the Stress-1 animals was smaller and the enhancement in the Stress-2 animals was greater than in the other groups. These results suggest that feeding oleic acid to rats exposed to water-immersion restraint further accelerated liver glycogen synthesis through the rise in liver SDH activity due to increased corticosterone secretion when compared with the effect from linoleic and alpha-linolenic acids.     

The efficient physiological strategy of a novel tomato genotype to adapt to chronic combined water and heat stress

• Climate change is increasing the frequency of high temperature shocks and water shortages, pointing to the need to develop novel tolerant varieties and to understand the mechanisms employed to withstand combined abiotic stresses.
• Two tomato genotypes, a heat-tolerant Solanum lycopersicum accession (LA3120) and a novel genotype (E42), previously selected as a stable yielding genotype under high temperatures, were exposed to single and combined water and heat stress. Plant functional traits, pollen viability and physiological (leaf gas exchange and chlorophyll a fluorescence emission measurements) and biochemical (antioxidant content and antioxidant enzyme activity) measurements were carried out. A Reduced Representation Sequencing approach allowed exploration of the genetic variability of both genotypes to identify candidate genes that could regulate stress responses.
• Both abiotic stresses had a severe impact on plant growth parameters and on the reproductive phase of development. Growth parameters and leaf gas exchange measurements revealed that the two genotypes used different physiological strategies to overcome individual and combined stresses, with E42 having a more efficient capacity to utilize the limiting water resources. Activation of antioxidant defence mechanisms seemed to be critical for both genotypes to counteract combined abiotic stresses. Candidate genes were identified that could explain the different physiological responses to stress observed in E42 compared with LA3120.
• Results here obtained have shown how new tomato genetic resources can be a valuable source of traits for adaptation to combined abiotic stresses and should be used in breeding programmes to improve stress tolerance in commercial varieties.

     

Development of oxidative stress and cell damage in the liver of rats with water-immersion restraint stress

We examined how oxidative stress and cell damage develop in the liver of rats subjected to water-immersion stress (WIRS). In rats subjected to WIRS for 1.5, 3 or 6 h, serum alanine aminotransferase and aspartate aminotransferase activities increased time-dependently. In the liver tissue, vacuolization and apoptosis occurred at 1.5 h of WIRS and vacuolization further developed without further appearance of apoptosis at 3 h or 6 h. Serum lipid peroxide (LPO) and NOx (nitrite/nitrate) concentrations increased at 3 h of WIRS and these increases were enhanced at 6 h. In liver tissue, increases in LPO and NOx concentrations and myeloperoxidase activity and decreases in ascorbic acid and reduced glutathione concentrations and superoxide dismutase activity occurred at 3 h of WIRS and these changes were enhanced at 6 h, although vitamin E concentration and xanthine oxidase activity were unchanged. These results indicate that oxidative stress in the liver of rats with WIRS develops after the appearance of cell damage in the tissue, and suggests that oxidative stress is caused through disruption of the antioxidant defense system and increases in NO generation and neutrophil infiltration in the liver, which may contribute to the progression of cell damage in the tissue.     

Effect of restraint stress on prolactin and corticosterone levels in streptozotocin-induced diabetic rats

Changes in neuroendocrine function have been shown to occur in diabetic animals. The aim of the present study was to examine both the prolactin (PRL) and corticosterone (CORT) responses to a short period of restraint stress after the animals had been made diabetic for six weeks. The streptozotocin - induced diabetic rats had resting CORT levels which were significantly higher than the control animals. Acute restraint significantly increased CORT levels in both the control and diabetic rats. The CORT levels after stress were higher in the diabetic rats. However, the magnitude of the response (percent increase) was less in these animals. The resting PRL levels were not significantly different in the diabetic and control animals. The PRL levels significantly increased in both the control and diabetic rats when they were exposed to the restraint stress. The PRL levels after stress were significantly less in the diabetic rats, indicating a blunted PRL stress response. These results indicate that the diabetic state can affect an animals PRL and CORT response to a new acute stress.