Lipid peroxidation in the adrenal cortex during exhausting stress

Under prolonged stress which is connected with exhaustion of functional resources of adrenal cortex the activation of lipid peroxidation processes in this gland was found. It is possible that the reason for such lipid peroxidation activation is the decrease in the content of adrenal cortex ascorbic acid and alpha-tocopherol.     

Effect of alpha-tocopherol on adrenal cortex functions under stress]

alpha-Tocopherol has been studied for its effect on lipid peroxidation and steroidogenesis in the adrenal cortices of rat and rabbit under stress. The vitamin is shown to exert an inhibitory effect on the lipid peroxidation developing under chronic stress. A biphasic pattern of the alpha-tocopherol effect on the steroidogenesis in the adrenal cortex is established: a decrease in the release of the steroids under the acute stress and maintaining of their levels under the chronic stress. A conclusion is drawn about a potential alpha-tocopherol application to correct the adrenal cortex function under stress.     

Relationship between mitochondrial lipid peroxidation and alpha-tocopherol levels in the guinea-pig adrenal cortex

Lipid peroxidation in mitochondria from the functionally distinct inner (zona reticularis) and outer (zona fasciculata + zona glomerulosa) zones of the guinea-pig adrenal cortex was investigated. Ferrous ion (Fe2+)-induced lipid peroxidation was far greater in inner than outer zone mitochondria. Ascorbic acid similarly initiated lipid peroxidation to a greater extent in inner zone mitochondrial preparations. Differences in the unsaturated fatty acid content of inner and outer zone mitochondria could not account for the regional differences in lipid peroxidation. Total fatty acid concentrations were greater in the outer than in the inner zone, and the relative amounts of each fatty acid were similar in the two zones. However, mitochondrial concentrations of alpha-tocopherol, an antioxidant known to inhibit lipid peroxidation, were approx. 5-times greater in the outer than inner zone. The results demonstrate that there are regional differences in mitochondrial lipid peroxidation in the adrenal cortex which may be attributable to differences in alpha-tocopherol content. Thus, alpha-tocopherol may serve to protect outer zone mitochondrial enzymes from the consequences of lipid peroxidation and thereby contribute to some of the functional differences between the zones of the adrenal cortex.     

Inhibition of lipid peroxidation by paraquat: site of inhibition in the cytochrome P-450-dependent steroid hydroxylase system from bovine adrenal cortex mitochondria

We have found that NADPH-dependent lipid peroxidation in bovine adrenal cortex mitochondria is strongly inhibited by paraquat. The site of the inhibition of the lipid peroxidation by paraquat has been examined. Paraquat neither inhibits NADPH-2,6-dichlorophenolindophenol nor NADPH-cytochrome c reductase activities. However, paraquat is able to retard the rate of reduction of cytochrome P-450 by NADPH. The spectrophotometric measurements provide the first evidence that lipid peroxidation in adrenal cortex mitochondria involves cytochrome P-450 and that the inhibitory effect of paraquat on lipid peroxidation is due to reoxidation of reduced cytochrome P-450 by the reagent.     

Mechanisms of human adaptation to hypoxia

The effects of adaptation to cold-and-hypoxic exposure on the cardiovascular system, lipid peroxidation and concentrations of adaptogenesis involved hormones were studied in male students. The two weeks cold- and hypoxic training was shown to be accompanied by a significant increase of apnea duration, reduced velocity of bradycardia development and a more rapid ECG post-cold and- hypoxic exposure normalization, as well as by inhibition of activation of adrenal cortex and thyroid gland after stress of different nature. The changes of the character of influences between the indices under study, were demonstrated. The correlation analysis showed an increase of the human's adaptive potential and a decrease of its dependence on the adrenal cortex hormones.     

Comparative determination of the potential for activating lipid peroxidation of the adrenal cortex, liver and heart in various animals

Studies have been made on the rate of spontaneous, ascorbate- and NADP.H-dependent lipid peroxidation in the adrenal cortex, liver heart of rats, rabbits and cattle. It was shown that in spite of some species differences in predisposition of tissues to lipid peroxidation. The highest rate of this process is characteristic of the liver of all the animals investigated.     

The relationship between NADPH-dependent lipid peroxidation and degradation of cytochrome P-450 in adrenal cortex mitochondria

The relationship between NADPH-dependent lipid peroxidation and the degradation of cytochrome P-450 has been studied in bovine adrenal cortex mitochondria. Malondialdehyde formation is accompanied by a corresponding decrease in total cytochrome P-450 content. Inhibitors of lipid peroxidation also prevent the loss of cytochrome P-450, further demonstrating a direct relationship between NADPH-dependent lipid peroxidation and degradation of P-450. To differentiate between cytochrome P-450(11)beta and P-450scc, steroid-induced difference spectra were used to evaluate P-450 degradation. These measurements provide the first evidence that both P-450's are degraded during NADPH-dependent lipid peroxidation with P-450(11)beta being much more susceptible to this process.     

Activation of lipid peroxidation in the adrenal cortex by metal ions

The processes of lipid peroxidation have been studied in bovine adrenal cortex in vitro. The lipid peroxidation rate in this tissue is shown to be dependent on the content of metal ions. EDTA, deferroxamine and penicyllamine inhibit spontaneous lipid peroxidation by 25, 50 and 42%, respectively. The ability to activate the process permits arranging metal ions in the following sequence: Fe2+ greater than Fe3+ greater than Cu2+ greater than Mg2+ greater than Mn2+. The maximum activation of lipid peroxidation is observed at Fe2+ and Fe3+ concentrations within the range of 5 x 10(-6) x 10(-4) M.     

Ferrous ion-mediated cytochrome P-450 degradation and lipid peroxidation in adrenal cortex mitochondria.

The relationship between the degradation reaction of cytochrome P-450 and lipid peroxidation was studied utilizing bovine adrenal cortex mitochondria. The two reactions were found to be closely correlated in terms of their response to storage of the mitochondrial preparation, stimulation by Fe2+, inhibition by EDTA and their initiation by cumene hydroperoxide. Both reactions were also found not to be inhibited by catalase, superoxide dismutase, 1,4-diazabicyclo-(2,2,2)-octane and alcohols, indicating that H2O2, superoxide, singlet oxygen and hydroxyl radicals do not participate in these reactions. Yet, diphenylamine proved to be a powerful inhibitor for both reactions, suggesting the involvement of a radical species. Cumene hydroperoxide could induce these two reactions at below 0.1 mM concentrations in the presence of molecular oxygen. The chemiluminescence observed during the Fe2+-mediated lipid peroxidation reaction which was not inhibited by either superoxide dismutase or 1,4-diazabicyclo-(2,2,2)-octane, was biphasic: one was a rapid burst; and the other was a slowly increasing emission. The latter portion of the emission of light coincided with the formation of malondialdehyde. These results indicate that in adrenal cortex mitochondria the degradation of cytochrome P-450 is closely related to lipid peroxidation.     

Dehydroepiandrosterone-induced lipid peroxidation in rat liver mitochondria

Administration of dehydroepiandrosterone (DHEA), a steroid hormone of the adrenal cortex which acts as a peroxisome proliferator and hepatocarcinogen in the rat, caused an increase in NADPH-dependent lipid peroxidation in mitochondria isolated from the liver, kidney and heart, but not from the brain. The effect of DHEA on rat liver mitochondrial lipid peroxidation became discernible after feeding steroid-containing diet (0.6% w/w) for 3 days, and reached maximal levels between 1 and 2 weeks. DHEA in the concentration range 0.001–0.02% did not significantly increase lipid peroxidation compared to the control. Lipid peroxidation was significantly enhanced in animals given a diet containing ≥ 0.05% DHEA. The addition of DHEA in the concentration range 0.1–100 μM to mitochondria isolated from control rats had no effect on lipid peroxidation. It seems, therefore, that the steroid effect is mediated by an intracellular process. Our data indicate that induction of mitochondrial membrane lipid peroxidation is an early effect of DHEA administration at pharmacological doses.     

Chloditan-induced changes in lipid peroxidation in the adrenals of dogs and guinea pigs

The effect of adrenocorticolytic drug chloditan (1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane;) on the content and the rate of lipid peroxidation in dog and guinea pig adrenals was studied. In adrenals of dogs and guinea the amount of malondialdehyde (MDA) was increased. In vitro spontaneous lipid peroxidation was delayed in adrenal homogenate of DDD-treated dogs. Spontaneous lipid peroxidation in adrenal homogenate was not decreased by feeding DDD in the guinea pig. DDD consumption did not affect on lipid peroxidation promoted by ascorbic acid and ferrous iron. The accumulation of MDA in dog and guinea pig adrenal homogenates was inhibited by NADPH.     

Oxidative Parameters in the Rat Brain of Chronic Mild Stress Model for Depression: Relation to Anhedonia-Like Responses

The chronic mild stress (CMS) protocol is widely used to evoke depression-like behaviors in the laboratory. Some animals exposed to CMS are resistant to the development of anhedonia, whereas the remaining are responsive, CMS-resilient and CMS-sensitive, respectively. The aim of this study was to examine the effects of chronic stress on oxidative parameters in the rat brain. The consumption of sweet food, protein and lipid oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, cortex and cerebellum were assessed. We found a significant increase in protein peroxidation (hippocampus and cortex), a significant increase in catalase activity (cortex, hippocampus and cerebellum) and a decrease in superoxide dismutase activity (cortex, hippocampus and cerebellum) in the CMS-sensitive group compared to the CMS-resilient group and normal controls as well as an increase in lipid peroxidation (cerebellum) in the CMS-sensitive and CMS-resilient groups compared to normal controls. However, there was no significant difference in protein peroxidation (cerebellum) and lipid peroxidation (cortex and hippocampus) among the three groups. In conclusion, our results indicate that the segregation into CMS-sensitive and -resilient groups based on sucrose intake is paralleled by significant differences in oxidative parameters. CMS induces oxidative damage and alterations in the activity of antioxidants which may lead to increased oxidative damage, irrespective of the anhedonia-like status of the stressed animals.     

Structure-Related Oxidative Damage in Rat Brain After Acute and Chronic Electroshock

The role of oxidative stress in electroconvulsive therapy-related effects is not well studied. The purpose of this study was to determine oxidative stress parameters in several brain structures after a single electroconvulsive seizure or multiple electroconvulsive seizures. Rats were given either a single electroconvulsive shock or a series of eight electroconvulsive shocks. Brain regions were isolated, and levels of oxidative stress in the brain tissue (cortex, hippocampus, striatum and cerebellum) were measured. We demonstrated a decrease in lipid peroxidation and protein carbonyls in the hippocampus, cerebellum, and striatum several times after a single electroconvulsive shock or multiple electroconvulsive shocks. In contrast, lipid peroxidation increases both after a single electroconvulsive shock or multiple electroconvulsive shocks in cortex. In conclusion, we demonstrate an increase in oxidative damage in cortex, in contrast to a reduction of oxidative damage in hippocampus, striatum, and cerebellum.     

Oxidative variables and antioxidant enzymes activities in the mdx mouse brain

Dystrophin is a protein found at the plasmatic membrane in muscle and postsynaptic membrane of some neurons, where it plays an important role on synaptic transmission and plasticity. Its absence is associated with Duchenne's muscular dystrophy (DMD), in which cognitive impairment is found. Oxidative stress appears to be involved in the physiopathology of DMD and its cognitive dysfunction. In this regard, the present study investigated oxidative parameters (lipid and protein peroxidation) and antioxidant enzymes activities (superoxide dismutase and catalase) in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx and normal C57BL10 mice. We observed (1) reduced lipid peroxidation in striatum and protein peroxidation in cerebellum and prefrontal cortex; (2) increased superoxide dismutase activity in cerebellum, prefrontal cortex, hippocampus and striatum; and (3) reduced catalase activity in striatum. It seems by our results, that the superoxide dismutase antioxidant mechanism is playing a protective role against lipid and protein peroxidation in mdx mouse brain.     

Oxidative variables and antioxidant enzymes activities in the mdx mouse brain

Dystrophin is a protein found at the plasmatic membrane in muscle and postsynaptic membrane of some neurons, where it plays an important role on synaptic transmission and plasticity. Its absence is associated with Duchenne's muscular dystrophy (DMD), in which cognitive impairment is found. Oxidative stress appears to be involved in the physiopathology of DMD and its cognitive dysfunction. In this regard, the present study investigated oxidative parameters (lipid and protein peroxidation) and antioxidant enzymes activities (superoxide dismutase and catalase) in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx and normal C57BL10 mice. We observed (1) reduced lipid peroxidation in striatum and protein peroxidation in cerebellum and prefrontal cortex; (2) increased superoxide dismutase activity in cerebellum, prefrontal cortex, hippocampus and striatum; and (3) reduced catalase activity in striatum. It seems by our results, that the superoxide dismutase antioxidant mechanism is playing a protective role against lipid and protein peroxidation in mdx mouse brain.     

Effects of hyperoxia and acrylonitrile on the phospholipase C isozyme protein levels in rat heart and brain

We previously showed that hyperoxia exerts oxidative stress on the rat cerebral cortex, and the protein levels of phospholipase C (PLC) -beta1 and -delta1, but not PLC-gamma1, were changed. Acrylonitrile (ACN) appears to induce astrocytomas through induction of oxidative stress on the rat brain selectively. This study compared hyperoxia or ACN treatments of rats with respect to lipid peroxidation and PLC levels in the heart and cerebral cortex. Treatment of rats with ACN promoted lipid peroxidation in the heart and cerebral cortex, the percent increase above control being greater in the cortex than heart. Hyperoxia did not cause significant increases in lipid peroxidation in the cerebral cortex or heart. In the ACN-treated cerebral cortex, significant increases in the PLC-beta1 and -delta1 in the cytosol, and PLC-gamma1 in the cytosolic and particulate fractions, and lysate were observed. In the rat heart, in which PLC-beta1 could not be detected, PLC-gamma1 and -delta1 were increased and decreased in the cytosolic and particulate fractions, respectively, by hyperoxia. In addition, the expression level of PLC-gamma1 was decreased in the lysate by the treatment. In the heart treated with ACN, there was no change in the level of PLC-gamma1, while PLC-delta1 was elevated in all fractions. These findings suggested that the expression levels of PLC isozymes are altered by hyperoxia and ACN, but there are apparent differences in these altered levels between the different levels of oxidative stress, and between the organs.     

Ferrous ion-mediated cytochrome P-450 degradation and lipid peroxidation in adrenal cortex mitochondria

The relationship between the degradation reaction of cytochrome $\text{P-450}$ and lipid peroxidation was studied utilizing bovine adrenal cortex mitochondria. The two reactions were found to be closely correlated in terms of their response to storage of the mitochondrial preparation, stimulation by Fe²⁺, inhibition by EDTA and their initiation by cumene hydroperoxide. Both reactions were also found not to be inhibited by catalase, superoxide dismutase, 1,4-diazabicyclo-(2,2,2)-octane and alcohols, indicating that H₂O₂, superoxide, singlet oxygen and hydroxyl radicals do not participate in these reactions. Yet, diphenylamine proved to be a powerful inhibitor for both reactions, suggesting the involvement of a radical species. Cumene hydroperoxide could induce these two reactions at below 0.1 mM concentrations in the presence of molecular oxygen. The chemiluminescence observed during the Fe²⁺-mediated lipid peroxidation reaction which was not inhibited by either superoxide dismutase or 1,4-diazabicyclo-(2,2,2)-octane, was biphasic: one was a rapid burst; and the other was a slowly increasing emission. The latter portion of the emission of light coincided with the formation of malondialdehyde. These results indicate that in adrenal cortex mitochondria the degradation of cytochrome $\text{P-450}$ is closely related to lipid peroxidation.     

Mulberry leaves protect rat tissues from immobilization stress-induced inflammation

The ability of the antioxidants in the mulberry leaves to protect Sprague-Dawley rats from injuries caused by immobilization stress was studied as an indicator of the tissue bioavailability of antioxidants. Nitrite level, lipid peroxidation and total antioxidant activity (TAA) in the plasma and tissues were measured. There were hypertrophy of the adrenal glands and kidneys, significant increased levels of nitrite in the plasma and adrenal glands, elevated thiobarbituric acid reactive substances (TBARS) in the plasma, kidneys and spleen, and a reduction of TAA in the plasma, liver, adrenal glands, kidneys and spleen of the immobilized rats. Antioxidants in the mulberry leaf extract suppressed the increase of nitrite and TBARS. Adrenal glands appeared to be the target organ of the antioxidants in the leaf extract. The low dose mulberry antioxidants were more effective than pure rutin (4 mg/day) to protect the cells against inflammation and peroxidation induced by stress.     

Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats

Melatonin has recently been suggested as an antioxidant that may protect neurons from oxidative stress. Acute ethanol administration produces both lipid peroxidation as an indicator of oxidative stress in the brain and impairs water-maze performance in spatial learning and memory tasks. The present study investigated the effect of melatonin against ethanol-induced oxidative stress and spatial memory impairment. The Morris water maze was used to evaluate the cognitive functions of rats. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were measured in the rat hippocampus and prefrontal cortex which form interconnected neural circuits for spatial memory. Acute administration of ethanol significantly increased TBARS levels in the hippocampus. Combined melatonin-ethanol treatment caused a significant increase in glutathione peroxidase activities and a significant decrease of TBARS in the rat hippocampus. In the prefrontal cortex, there was only a significant decrease of TBARS levels in the combined melatonin-ethanol receiving group as compared to the ethanol-treated group. Melatonin did not affect the impairment of spatial memory due to acute ethanol exposure, but melatonin alone had a positive effect on water maze performances. Our study demonstrated that melatonin decreased ethanol-induced lipid peroxidation and increased glutathione peroxidase activity in the rat hippocampus.     

Lifelong caloric restriction prevents age-induced oxidative stress in the sympathoadrenal system of Fischer 344 x Brown Norway rats

Aging is associated with oxidative damage and an imbalance in redox signaling in a variety of tissues, yet little is known about the extent of age-induced oxidative stress in the sympathoadrenal system. Lifelong caloric restriction has been shown to lower levels of oxidative stress and slow the aging process. Therefore, the aims of this study were twofold: (1) to investigate the effect of aging on oxidative stress in the adrenal medulla and hypothalamus and (2) determine if lifelong 40% caloric restriction (CR) reverses the adverse effects of age-induced oxidative stress in the sympathetic adrenomedullary system. Adult (18 months) and very old (38 months) male Fischer 344 x Brown Norway rats were divided into ad libitum or 40% CR groups and parameters of oxidative stress were analyzed in the adrenal medulla and the hypothalamus. A significant age-dependent increase in lipid peroxidation (+20%, P < 0.05) and tyrosine nitration (+111%, P < 0.001) were observed in the adrenal medulla while age resulted in a reduction in the protein expression of key antioxidant enzymes, CuZnSOD (−27%, P < 0.01) and catalase (−27%, P < 0.05) in the hypothalamus. Lifelong CR completely prevented the age-induced increase in lipid peroxidation in the adrenal medulla and restored the age-related decline in antioxidant enzymes in the hypothalamus. These data indicate that aging results in a significant increase in oxidative stress in the sympathoadrenal system. Importantly, lifelong CR restored the age-related changes in oxidative stress in the adrenal medulla and hypothalamus. Caloric restriction could be a potential non-pharmacological intervention to prevent increased oxidative stress in the sympathetic adrenomedullary system with age.