Hydroxyl Radical Content Research Articles

Eugenol-inhibited root growth in Avena fatua involves ROS-mediated oxidative damage

Plant essential oils and their constituent monoterpenes are widely known plant growth retardants but their mechanism of action is not well understood. We explored the mechanism of phytotoxicity of eugenol, a monoterpenoid alcohol, proposed as a natural herbicide. Eugenol (100–1000 µM) retarded the germination of Avena fatua and strongly inhibited its root growth compared to the coleoptile growth. We further investigated the underlying physiological and biochemical alterations leading to the root growth inhibition. Eugenol induced the generation of reactive oxygen species (ROS) leading to oxidative stress and membrane damage in the root tissue. ROS generation measured in terms of hydrogen peroxide, superoxide anion and hydroxyl radical content increased significantly in the range of 24 to 144, 21 to 91, 46 to 173% over the control at 100 to 1000 µM eugenol, respectively. The disruption in membrane integrity was indicated by 25 to 125% increase in malondialdehyde (lipid peroxidation byproduct), and decreased conjugated diene content (~10 to 41%). The electrolyte leakage suggesting membrane damage increased both under light as well as dark conditions measured over a period from 0 to 30 h. In defense to the oxidative damage due to eugenol, a significant upregulation in the ROS-scavenging antioxidant enzyme machinery was observed. The activities of superoxide dismutases, catalases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases were elevated by ~1.5 to 2.8, 2 to 4.3, 1.9 to 5.0, 1.4 to 3.9, 2.5 to 5.5 times, respectively, in response to 100 to 1000 µM eugenol. The study concludes that eugenol inhibits early root growth through ROS-mediated oxidative damage, despite an activation of the antioxidant enzyme machinery.

Effects of a dietary administration of purple coneflower (Echinacea purpurea) on growth, antioxidant activities and 8 miRNAs expressions in crucian carp (Carassius auratus)

Echinacea purpurea (EP), a globally popular herbal medicine, has been used to treat various diseases in human and animals. However, little has been reported about its effects in fish. In this study, crucian carp (Carassius auratus) were selected to evaluate the effects of EP on growth performance and antioxidant response and the expressions of microRNAs. The results showed EP could stimulate the growth of crucian carp with the best effect was observed at dose of 4 g kg−1. In serum, the content of hydroxyl radical (·OH) and malondialdehyde (MDA) decreased by EP supplementation, whereas the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) increased. Similarly, the content of ·OH decreased, and the activities of CAT, GPX and GR increased in liver of crucian carp. Furthermore, in livers of crucian carp, EP supplements upregulated the expressions of the microRNAs (miR-16, miR-21, miR-125b, miR-146a, miR-155, miR-181a and miR-223), which had been confirmed to participate in regulating antioxidant and immune function in mammals. Our results suggest EP supplements in diets stimulated growth performance and antioxidant response of crucian carp. In liver, the upregulation of specific miRNAs may participate in the antioxidant effects of EP diets.

Is There a Correlation Between In Vitro Antioxidant Potential and In Vivo Effect of Carvacryl Acetate Against Oxidative Stress in Mice Hippocampus?

This study investigated in vitro and in vivo antioxidant potential of carvacryl acetate (CA), a derivative of carvacrol, monoterpenic component of oregano. The correlation between in vitro and in vivo CA effects was also determined. In vitro tests measured thiobarbituric acid reactive species content, nitrite formation and hydroxyl radical levels. In vivo tests measured thiobarbituric acid reactive species content, nitrite concentration and reduced glutathione (GSH) levels, as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase activities were measured, using mice hippocampus. The CA administrations for in vivo tests were intraperitoneally and acutely improved. CA reduced lipid peroxidation, nitrite and hydroxyl radical contents in vitro as well as lipid peroxidation and nitrite content in vivo. It also increased reduced GSH levels and GPx as well as catalase activities. Moreover, CA required a lower concentration to inhibit 50% of free radicals measured in vitro than trolox. There was significant negative correlation between in vitro nitrite levels and in vivo reduced GSH levels; in vitro nitrite content and in vivo GPx activity as well as in vitro hydroxyl radical levels and in vivo SOD activity. To date, this is the first study which suggests vitro and in vivo antioxidant potential to this monoterpene and the correlation between these parameters.

Salinity induced the changes of root growth and antioxidative responses in two wheat cultivars

This study aimed to investigate the inhibitory mechanism of root growth and to compare antioxidative responses in two wheat cultivars, drought-tolerant Ningchun and drought-sensitive Xihan, exposed to different NaCl concentrations. Ningchun exhibited lower germination rate, seedling growth, and lipid peroxidation than Xihan when exposed to salinity. The loss of cell viability was correlated with the inhibition of root growth induced by NaCl stress. Moreover, treatments with H2O2 scavenger dimethylthiourea and catalase (CAT) partly blocked salinity-induced negative effects on root growth and cell viability. Besides, the enhancement of superoxide radical and H2O2 levels, and the stimulation of CAT and diamine oxidase (DAO) as well as the inhibition of glutathione reductase (GR) were observed in two wheat roots treated with salinity. However, hydroxyl radical content increased only in Xihan roots under NaCl treatment, and the changes of soluble peroxidase (POD), ascorbate peroxidase (APX), superoxide dismutase (SOD), and cell-wall-bound POD activities were different in drought-tolerant Ningchun and drought-sensitive Xihan exposed to different NaCl concentrations. In conclusion, salinity might induce the loss of cell viability via a pathway associated with extracellular H2O2 generation, which was the primary reason leading to the inhibition of root growth in two wheat cultivars. Here, it was also suggested that increased H2O2 accumulation in the roots of drought-tolerant Ningchun might be due to decreased POD and GR activities as well as enhanced cell-wall-bound POD and DAO ones, while the inhibition of APX and GR as well as the stimulation of SOD and DAO was responsible for the elevation of H2O2 level in drought-sensitive Xihan roots.

Degradation of cellulose at the wet–dry interface. II. Study of oxidation reactions and effect of antioxidants

To better understand the degradation of cellulose upon the formation of a tideline at the wet–dry interface when paper is suspended in water, the production of chemical species involved in oxidation reactions was studied. The quantitation of hydroperoxides and hydroxyl radicals was carried out in reverse phase chromatography using triphenylphosphine and terephthalic acid, respectively, as chemical probes. Both reactive oxygen species were found in the tideline immediately after its formation, in the range of micromoles and nanomoles per gram of paper, respectively. The results indicate that hydroxyl radicals form for the most part in paper before the tideline experiment, whereas hydroperoxides appear to be produced primarily during tideline formation. Iron sulfate impregnation of the paper raised the production of hydroperoxides. After hygrothermal aging in sealed vials the hydroxyl radical content in paper increased significantly. When aged together in the same vial, tideline samples strongly influenced the degradation of samples from other areas of the paper (multi-sample aging).Different types of antioxidants were added to the paper before the tideline experiment to investigate their effect on the oxidation reactions taking place. In samples treated with iron sulfate or artificially aged, the addition of Irgafos 168 (tris(2,4-ditert-butylphenyl) phosphate) and Tinuvin 292 (bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate) reduced the concentration of hydroperoxides and hydroxyl radicals, respectively. Tinuvin 292 was also found to considerably lower the rate of cellulose chain scission reactions during hygrothermal aging of the paper.

Effects of adenosine receptor antagonists on the in vivo LPS-induced inflammation model of Parkinson's disease.

The study shows effects of the nonselective adenosine A1/A2A receptor antagonist caffeine and the selective A2A receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A2A receptor density in the rat striatum. Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of adenosine, glutamate, and hydroxyl radical on the ipsilateral side 24 h after LPS administration. Caffeine (10 and 20 mg/kg i.p.) and KW6002 (1.5 and 3 mg/kg i.p.) given once daily for 6 days and on the 7th day 2 h before and 4 h after LPS injection reversed the LPS-induced changes in extracellular levels of DA, adenosine, glutamate, and hydroxyl radical production. Moreover, LPS-induced decrease in the striatal A2A receptor density was increased by caffeine and KW6002. In order to show the late LPS effect on oxidative damage of DA neurons, the contents of DA, DOPAC, HVA, and hydroxyl radical were determined 72 h after LPS (10 μg) administration into both striata. LPS decreased striatal and substantia nigra content of DA, DOPAC, and HVA while increased striatal but not nigral content of hydroxyl radical. Caffeine (20 mg/kg) and KW60002 (3 mg/kg) given once daily for 6 days and on the 7th day 2 h before and 4 h after intrastriatal injection of LPS normalized the content of DA and its metabolites in both brain regions as well as decreased LPS-induced increase in the striatal level of hydroxyl radical. In conclusion, our data demonstrated antioxidant effects of caffeine and KW6002 in the inflammatory model of PD.

Effects of postharvest sodium silicate treatment on pink rot disease and oxidative stress-antioxidative system in muskmelon fruit

Sodium silicate (Si) at 100 mM was used as a postharvest treatment agent of induction resistance on muskmelon (Cucumis melon L. cv. Yindi) to investigate the mechanism of controlling pink rot disease, which caused by Trichothecium roseum. Si treatment significantly reduced (P < 0.05) the lesion diameter of melons inoculated with T. roseum during storage. Si treatment increased the content of superoxide (O2•−) and could be further raised by challenged with T. roseum inoculation. The content of hydroxyl radical (·OH) in inoculated fruit was also increased. Both malondialdehyde (MDA) and hydrogen peroxide (H2O2) were also accumulated with Si treatment and challenged inoculation. Si treatment maintained membrane integrity in non-inoculated fruit, as compared to untreated control. Si treatment and challenge inoculation significantly (P < 0.05) increased the activity of superoxide dismutase (SOD), glutathione reductase (GR), peroxidase (POD), and polyphenoloxidase (PPO), while markedly decreased the activity of catalase (CAT) and ascorbic peroxidase (APX). Si treatment and challenge inoculation also enhanced the content of ascorbic acid (ASA) and glutathione (GSH). These findings suggested that the effects of sodium silicate on postharvest disease in muskmelon fruit may be associated with the elicitation of antioxidant defense system in fruit.

Probing a family GH11 endo-β-1,4-xylanase inhibition mechanism by phenolic compounds: Role of functional phenolic groups

Abstract Phenolic compounds generated from lignin degradation during the pre-treatment step in the process of producing bioethanol from lignocellulosic biomass are known to be inhibitory to enzymatic hydrolysis and fermentation. The inactivation mechanism of a GH11 endoxylanase (Tx-Xyl) by several phenolic compounds varying in their hydroxyl and methoxyl radical content was investigated. Apparent kinetic inactivation parameters were measured as an approximate index of the inhibitory effects. All the tested aromatic compounds had strong negative impact on enzyme activity and kinetic analysis revealed non competitive multi-site inhibition mechanism. The interactions between Tx-Xyl and the phenolic compounds were further studied by steady-state (tryptophan) fluorescence spectroscopy. Changes in λ max of emission and quenching of fluorescence intensity indicated changes in the microenvironment of tryptophan residues. In agreement with the kinetic parameters, the fluorescence derived binding constants evidenced higher enzyme–phenolics interaction affinity with increasing phenolic hydroxyl radical content, suggesting clear correlations of such radicals with the inhibitory effects. Results indicated that the inhibitory effects of phenolic compounds on Tx-Xyl activity are most likely brought about by conformational alterations of the enzyme protein inducing steric inactivation.

Modulation of protein tyrosine phosphorylation in gastric mucosa during re-epithelization processes

To investigate the role of protein tyrosine phosphorylation in gastric wound formation and repair following ulceration. Gastric lesions were induced in rats using restraint cold stress. To investigate the effect of oxidative and nitrosative cell stress on tyrosine phosphorylation during wound repair, total activity of protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTP), antioxidant enzymes, nitric oxide synthase (NOS), 2',5'-oligoadenylate synthetase, hydroxyl radical and zinc levels were assayed in parallel. Ulcer provocation induced an immediate decrease in tyrosine kinase (40% in plasma membranes and 56% in cytosol, P < 0.05) and phosphatase activity (threefold in plasma membranes and 3.3-fold in cytosol), followed by 2.3-2.4-fold decrease (P < 0.05) in protein phosphotyrosine content in the gastric mucosa. Ulceration induced no immediate change in superoxide dismutase (SOD) activity, 30% increase (P < 0.05) in catalase activity, 2.3-fold inhibition (P < 0.05) of glutathione peroxidase, 3.3-fold increase (P < 0.05) in hydroxyl radical content, and 2.3-fold decrease (P < 0.05) in zinc level in gastric mucosa. NOS activity was three times higher in gastric mucosa cells after cold stress. Following ulceration, PTK activity increased in plasma membranes and reached a maximum on day 4 after stress (twofold increase, P < 0.05), but remained inhibited (1.6-3-fold decrease on days 3, 4 and 5, P < 0.05) in the cytosol. Tyrosine phosphatases remained inhibited both in membranes and cytosol (1.5-2.4-fold, P < 0.05). NOS activity remained increased on days 1, 2 and 3 (3.8-, 2.6-, 2.2-fold, respectively, P < 0.05). Activity of SOD increased 1.6 times (P < 0.05) days 4 and 5 after stress. Catalase activity normalized after day 2. Glutathione peroxidase activity and zinc level decreased (3.3- and 2-fold, respectively, P < 0.05) on the last day. Activity of 2',5'-oligoadenylate synthethase increased 2.8-fold (P < 0.05) at the beginning, and 1.6-2.3-fold (P < 0.05) during ulcer recuperation, and normalized on day 5, consistent with slowing of inflammation processes. These studies show diverse changes in total tyrosine kinase activity in gastric mucosa during the recovery process. Oxidative and nitrosative stress during lesion formation might lead to the observed reduction in tyrosine phosphorylation during ulceration.

Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats

To investigate the correlation of perihematomal free radical level and neuronal apoptosis following the intracerebral hemorrhage (ICH). Animals were randomly divided into 4 groups: sham operation group, model group, 1 mg/kg edaravone group, and 3 mg/kg edaravone group. Each group was then divided into seven subgroups, in which the rats were correspondingly killed at 6 h, 12 h, 24 h, 48 h, 72 h, 7 d or 14 d (n = 1 in each subgroup of the sham group, and n = 6 in each subgroup of the other 3 groups). By Horseley-Clarke technique, autoblood (80 microL) were administered into the left caudate putamen of SD rats in a double administration-withdrawal way. Rats in the sham group were needled in but not administered with autoblood. The ICH model was then evaluated by Bederson's scale. Around the hematoma, the levels of malonaldehyde (MDA) and hydroxyl radical were tested by spectrophotometer, and the process of apoptosis was tested by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method. (1) ICH significantly increased the levels of MDA and hydroxyl radicals. Significant differences in MDA and hydroxyl radical contents were observed among the four groups. (2) In the sham group, a small number of TUNEL-positive cells were found. In the other three groups, the TUNEL-positive cells were observed at 6 h, increased significantly at 24 h, and reached peak level at 3 d, then fell profoundly at 7 d, but remained detectable at 14 d. (3) The positive correlation existed between apoptosis and free radical level (r = 0.2003), and existed between apoptosis and MDA content (r = 0.6563) in the brain. Post-hemorrhagic apoptosis was related to the production of free radicals, indicating that the elevated free radicals following the ICH could induce neuron and glial cell apoptosis.

Cortical dopaminergic neurotransmission in rats intoxicated with lead during pregnancy. Nitric oxide and hydroxyl radicals formation involvement

It is well established that low level Pb-exposure is associated with a wide range of cognitive and neurobehavioral dysfunctions in children. In fact, Pb-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum — the anatomical sites which are crucial in modulating emotional response, memory and learning. Previously it was also shown that nitric oxide (NO) signaling pathway as well as glutamatergic neurotransmission are both involved in brain development, neurotoxicity and neurodegeneration processes whereas Pb 2+ interfere with both. For this reason we investigated the effect of ontogenetic Pb 2+ exposure on dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) of rats after amphetamine (AMPH) and/or 7-nitroindazole (7-NI) administration. Furthermore, the possible role of oxidative stress in Pb 2+-induced neurotoxicity in prenatally Pb 2+-treated rats was explored in the content of hydroxyl radical (HO •) species in mPFC after AMPH and/or 7-NI injection, assessed by HPLC analysis of 2.3-dihydroxybenzoic acid (2.3-DHBA) — spin trap product of salicylate. As shown, the results of this study suggest that Pb 2+ exposure during intrauterine life did not substantially affect cortical dopaminergic neurotransmission in adult offspring rats evaluated by means of microdialysis of mPFC and the content of the cortical HO •. It is likely that striatum, nucleus accumbens or other dopamine rich brain areas are more intricately associated with Pb 2+ precipitated behavioral, dopamine — dependent impairments observed in mammalians.

애엽 추출물 섭취가 ICR 마우스의 피부조직에 미치는 항산화 효과

애엽 추출물에 대한 ICR 마우스의 피부 조직에 대한 항산화작용 및 산화적 스트레스에 미치는 영향을 조사하였다. 애엽 추출물(mugwort extract: ME)을 섭취한 식이군의 경우, 추출물의 농도에 따라 피부조직의 단백질 함량이 대조군에 비해 3.1%～11.1% 증가하였다. 활성산소 중 히드록시 라디칼 함량은 애엽 추출물 식이군에서 10.4%～17.4%의 유의적인 감소 효과가 인정되었으며, 그리고 산화적 스트레스로써 산화단백질의 함량도 애엽 추출물 식이군(ME-100, ME-200)이 대조군에 비해 각각 15.2%와 17.1%의 유의적인 감소를 보였다(p＜0.05). 과산화지질함량은 애엽 추출물의 농도증가에 따라 감소되는 경향을 보여주었으나, 통계적인 유의성은 없었다. 수퍼옥시드 디스무타아제 활성은 ME-100 군과 ME-200 군에서 각각 15.0%와 23.3%의 유의적인 증가가 있었고, 또한 애엽 추출물의 농도가 증가할수록 카탈라아제 활성도 증가하는 것으로 나타났다. 애엽 추출물의 섭취가 피부의 활성산소를 제거하고 산화적 스트레스를 억제하며, 항산화효소의 활성을 증가시켜 피부의 노화현상을 억제시키는 효과가 있음을 확인할 수 있었다. 강력한 항산화제인 아스코르브산과 비교하여도 손색이 없는 높은 활성을 보였다. 이와 같은 결과는 피부 건강기능 식품과 음료 소재로서 애엽의 이용 가능성을 제시한다.

Cardiovascular oxidative stress is reduced by an ACE inhibitor in a rat model of streptozotocin-induced diabetes

Blockade of the renin-angiotensin system (RAS) reduces cardiovascular morbidity and mortality in diabetic patients. Ang II-mediated generation of reactive oxygen species (ROS) has been suggested to be involved in several diabetic complications. We investigated whether the inhibition of Ang II production with an ACE inhibitor (ACEi) reduces oxidative stress and limits structural cardiovascular remodeling in a rat model of streptozotocin (STZ)-induced diabetes. Diabetic rats were treated for 7 weeks with an ACEi (lisinopril, 5 mg/kg/d), an antioxidant ( N-acetyl- l-cysteine (NAC), 0.5 g/kg/d) and their combination. At sacrifice, ROS in the myocardium and thoracic aorta, LV myocyte number and size and aorta morphology were determined by quantitative histological methods. Superoxide and hydroxyl radical content, detected by dihydroethidium (DHE) and 8-hydroxydeoxyguanosine (8-OHdG), were 6.7 and 4.5-fold, respectively, higher in diabetic myocardium than in non-diabetic controls ( p < 0.001). The amount of superoxide was 5-fold higher in the thoracic aorta of diabetic rats compared to controls ( p < 0.001). Diabetes caused a modest increase in myocyte volume (+ 13%, p < 0.01), a reduction of LV myocyte number (− 43%, p < 0.001), an accumulation of collagen around coronary arterioles (1.9-fold increase, p < 0.01) and a decrease in arterial elastin / collagen ratio (− 63%, p < 0.001) compared to controls. Treatment with the ACEi attenuated ROS formation and prevented phenotypic changes in the heart (cardiomyocyte hypertrophy, perivascular fibrosis) and in the aorta of diabetic rats to the same extent as NAC. The absence of an additive effect, suggests a common mechanism of action, through the reduction of oxidative stress.

Relationship between oxidative stress and apoE phenotype in Alzheimer's disease.

To investigate the relationship between oxidative stress and apoE phenotype in dementia of Alzheimer type (DAT). Hydroxyl radical content in blood, superoxide dismutase (SOD) activity in red blood cells (RBC) and plasma, Cu,Zn-SOD protein content in RBC, and apoE phenotype were determined in 24 DAT patients and 25 controls. DAT patients with the apoE4 phenotype showed higher hydroxyl radical levels than DAT patients without the apoE4 phenotype or controls. SOD activities and Cu,Zn-SOD protein levels in RBC of DAT patients with and without the apoE4 phenotype showed no significant differences, but values in both patient groups were lower than in controls. The apoE4 phenotype was more prevalent in DAT patients than in controls. DAT patients with the apoE4 phenotype were younger at disease onset than DAT patients without the apoE4 phenotype. Our findings suggest that apoE4 and SOD individually influence oxidative stress in DAT.

Degradation of Atrazine into Ammeline by Combined Ozone/Hydrogen Peroxide Treatment in Water

The aqueous ozone treatment of atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine] in the presence of hydrogen peroxide was reinvestigated using a new tandem solid-phase extraction procedure which includes a C18 reverse phase support and a strong cation exchanger. In this way, both chlorotriazines and the more polar hydroxytriazines could be analyzed to establish total molar balances of degradation products vs the initial pesticide in the 45−55% range. In all the experimental conditions examined (treatment rates, pH, and eventual presence of carbonates), ammeline (2,4-diamino-6-hydroxy-s-triazine) was found as the major end-product (20% at pH 8). 2-Chloro-4,6-diamino-s-triazine was produced competitively, and the ratio between both products was dependent on the hydroxyl radical content. A number of new intermediates were identified i.e. amino-aldehydes and a carbinolamine. The carbinolamine functionality is of great interest since being involved in the dealkylation process of the triazinic am...

Glutathione status and reactive oxygen generation in tissues of young and old exercised rats

The effects of exercise on the generation of active oxygen species and radical-scavenging capacity were studied in physically active and sedentary young and old rats. Exercise increased the hydroxyl radical content in all tissues of physically active young rats, except in the plasma. In old rats, the basal level of the radical increased significantly in plasma, heart, and skeletal muscles, but decreased in liver; and physical activity decreased it to that of young rats in most cases. With exercise, the content of reduced glutathione increased in plasma, heart, and skeletal muscles of young rats, whereas that of oxidized glutathione markedly decreased in liver and increased in brain and white gastrocnemius muscle. The total glutathione levels in these tissues changed in a similar way, indicating that glutathione was released from the pool in the liver. In rats allowed to run voluntarily for 5 weeks, the effects were more pronounced than in the sedentary rats. The ratio of reduced to total glutathione, which indicates the capacity to reduce glutathione, increased in plasma, heart, and soleus muscle of sedentary young rats after exercise, and increased further in those undergoing physical activity. In old rats, the reduced glutathione level increased in plasma, heart, liver, and brain, even though the total decreased. These results suggest that physical activity enhances the endogenous ability to defend against oxidative stress. In old rats, even though glutathione synthesis is decreased, the regenerating capacity seems to be increased in order to compensate for the increased oxidative stress.

Estimating hydroxyl radical content in rat brain using systemic and intraventricular salicylate: impact of methamphetamine.

Free radicals have been implicated in the etiology of many neurodegenerative conditions. Yet, because these species are highly reactive and thus short-lived it has been difficult to test these hypotheses. We adapted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quantifiable products, 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. After systemic (100 mg/kg i.p.) or intraventricular (4 mumol) administration of salicylate, the amount of DHBA in striatal tissue correlated with tissue levels of salicylate. After systemic salicylate, the ratio of total DHBA to salicylate in neostriatum was at least 10-fold higher than that observed after central salicylate. In addition, systemic salicylate resulted in considerably higher concentrations of 2,3- and 2,5-DHBA in plasma than in brain. Therefore, a large portion of the DHBA present in brain after systemic salicylate may have been formed in the periphery. A neurotoxic regimen of methamphetamine increased the concentration of DHBA in neostriatum after either central or systemic administration of salicylate. The increase in 2,3-DHBA after the central administration of salicylate was significant at 2 h, but not at 4 h, after the last dose of methamphetamine. These results suggest that (1) when assessing specific events in brain, it is preferable to administer salicylate centrally, and (2) neurotoxic doses of methamphetamine increase the hydroxyl radical content in brain in a time-dependent manner.

Hydroxyl radical generation and nitric oxide synthase activity in Fisher 344 × Brown-Norway F1 rat brain

Hydroxyl radical production in the cerebral cortex, striatum and hippocampus of young (6 months), middle-aged (15 months) and old (28 months) Fisher 344 × Brown-Norway F1 rats was quantitated by measuring the salicylate hydroxyl radical-trapping product, 2,5-dihydroxybenzoic acid. The levels of hydroxyl radical between different age groups in each region examined were not statistically different. In all regions, with the eception of hippocampus from old rats which had a lower content of hydroxyl radical, the levels of hydroxyl radical were higher for middle-aged and old rats than young ones. There was no regional difference in the production of hydroxyl radicals, except that the level was significantly higher in striatum than in cortex for 15-month-old rats. The cerebral cortical nitric oxide synthase activities were similar in the three age groups studied.