Effects of pretreatment with an indeno-indole compound on lipid peroxidation in the cortex and medulla of rabbit kidneys after ischaemia-reperfusion

The effects of 60 min of ischaemia with or without reoxygenation in vivo or in vitro on lipid peroxidation in cortical and medullary tissue from rabbit kidneys were measured as production of thiobarbituric acid-reactive substances (TBARS). Lipid peroxidation was more pronounced in medullary tissue compared with cortical tissue. The highest TBARS production was found in medullary slices subjected to reoxygenation in vitro immediately after 1 h of ischaemia. Reperfusion in vivo before reoxygenation in vitro attenuated the TBARS formation during subsequent in vitro incubation. Pretreatment of the rabbits with an indeno-indole compound (code name H 290/51) reduced the TBARS formation after 60 min of ischaemia and reoxygenation in vitro towards control values.     

Oxidative damage: The biochemical mechanism of cellular injury and necrosis in choline deficiency

Oxidative stress and damage are characterized by decreased tissue antioxidant levels, consumption of tissue α-tocopherol, and increased lipid peroxidation. These processes occur earlier than necrosis in the liver, heart, kidney, and brain of weanling rats fed a choline deficient (CD) diet. In tissues, water-soluble antioxidants were analyzed as total reactive antioxidant potential (TRAP), α-tocopherol content was estimated from homogenate chemiluminescence (homogenate-CL), and lipid peroxidation was evaluated by thiobarbituric acid reactive substances (TBARS). Histopathology showed hepatic steatosis at days 1-7, tubular and glomerular necrosis in kidney at days 6 and 7, and inflammation and necrosis in heart at days 6 and 7. TRAP levels decreased by 18%, 48%, 56%, and 66% at day 7, with t_1/2 (times for half maximal change) of 2.0, 1.8, 2.5, and 3.0 days in liver, kidney, heart, and brain, respectively. Homogenate-CL increased by 97%, 113%, 18%, and 297% at day 7, with t_1/2 of 2.5, 2.6, 2.8, and 3.2 days in the four organs, respectively. TBARS contents increased by 98%, 157%, 104%, and 347% at day 7, with t_1/2 of 2.6, 2.8, 3.0, and 5.0 days in the four organs, respectively. Plasma showed a 33% decrease in TRAP and a 5-fold increase in TBARS at day 5. Oxidative stress and damage are processes occurring earlier than necrosis in the kidney and heart. In case of steatosis prior to antioxidant consumption and increased lipid peroxidation, no necrosis is observed in the liver.     

Neuroprotective effects of tramadol on cerebral injuries caused by hind limb ischaemia/reperfusion in rats

Skeletal muscle ischaemia–reperfusion-induced acute remote injury is mediated by activated neutrophils and formation of free radicals. Several investigators have demonstrated that the opioid pathway is involved in tissue preservation during hypoxia or ischaemia. Tramadol hydrochloride is an effective analgesic used for severe acute and chronic pain conditions. The present study was designed to investigate the potential protective effects of tramadol hydrochloride on cerebral oxidative stress and damage as well as lipid peroxidation, brain oedema and histological changes induced by hind limb ischaemia and reperfusion injury in rats. Thirty-six male Wistar rats were randomly allocated into two experimental groups: ischaemia–reperfusion (group I) and ischaemia–reperfusion + tramadol hydrochloride (group II). Hind limb ischaemia was induced by clamping the femoral artery. After 2-h ischaemia, the clamp from the femoral vessels was removed and the animal underwent 24-h reperfusion. Tramadol hydrochloride was given intravenously at a dose of 20 mg/kg, immediately before reperfusion. After reperfusion, animals were euthanized and the cerebral structure, lipid peroxidation and brain oedema in the cerebral tissue were assessed. Histopathological assessment of cerebral injury was split into four grades. The extent of lipid peroxidation was measured by estimating the amount of malondialdehyde. Brain oedema was calculated as the percentage water content of the brain. Brain oxidative stress and damage were significantly attenuated by treatment with tramadol hydrochloride. Compared with the ischaemia–reperfusion group, histological changes in brain tissues (p?p?P?相似文献   

The effect of a synthetic hexadentate iron chelator (CP130) and desferrioxamine on rabbit kidneys exposed to cold and warm ischaemia

The effect of CP130 (a synthetic hexadentate pyridinone iron chelator) on the formation of two markers of lipid peroxidation (TBA-reactive material and Schiff's bases) in rabbit kidneys following a 72 h period of cold (0–4°C) ischaemia was investigated by either adding CP130 to the flush/storage solution (hypertonic citrate solution) or by administering the agent intravenously 15 min before removal of the organs. In both cases, CP130 blocked the adverse rises in lipid peroxidation caused by ischaemia and subsequent reoxygenation of the homogenatesin vitro. Both CP130 and desferrioxamine (DFX) (administered intravenously 15 min before ischaemia and 5 min before reperfusion) were also found to significantly reduce post-ischaemic rates ofin vitro lipid peroxidation in kidneys rendered warm ischaemic for 90 min followed by reperfusion for 5 or 60 minin situ. Kidneys exposed to warm ischaemia and reperfusion developed interstitial and intracellular oedema, congestion and haemorrhage. DFX administration had little effect on the histological outcome, whereas CP130 significantly reduced interstitial oedema (at 6 min reperfusion compared to the DFX-treated group), intracellular oedema (at 60 min reperfusion compared to the DFX-treated group) and congestion (at 5 min reperfusion compared with a control group not given any agent). It is concluded that while CP130 and DFX exhibited similar antioxidant properties, CP130 provided better protection from ischaemia/reperfusion injury at the histological level. Synthetic iron chelators may therefore be of benefit in clinical organ transplantation by protecting against tissue damage caused by prolonged ischaemia.     

Lipid peroxidation and antioxidative vitamins under extreme endurance stress*

The aim of this study was to examine whether extreme endurance stress of trained athletes can influence lipid peroxidation and muscle enzymes. A randomized and placebo-controlled study was carried out on 24 trained long-distance runners who were substituted with α-tocopherol (400 I.U. d^-1) and ascorbic acid (200 mg d^-1) during 4.5 weeks prior to a marathon race. The serum concentrations of retinol, ascorbic acid, β-carotene, α-tocopherol, malondialdehyde (TBARS) and uric acid as well as gluthation peroxidase (GSH Px) and catalase were measured 4.5 weeks before (A), immediately before (B), immediately after (C) and 24 h after (D) the course. After competition (C) TBARS serum concentrations of the athletes (n= 22) decreased in both groups (P < 0.0001). The ascorbic acid serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.01), from (B) to (C) (P < 0.001) and in the placebo group a significant increase from (B) to (C) (P < 0.01) was observed. The α-tocopherol serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.001) and from (B) to (C) (P < 0.05). The enzymes glutathione peroxidase (GSH Px) and catalase measured in erythrocytes as well as the serum selenium levels did not show significant differences at any time. A significant increase of CK concentration was observed from (C) to (D) in the supplemented group (P < 0.01) and in the placebo group (P < 0.001). The increase of CK serum concentration is remarkably lower in the supplemented group compared with the placebo group (P < 0.01). It is concluded that endurance training coupled with antioxidant vitamin supplementation reduces blood CK increase under exercise stress.     

Effect of pre-treatment with desferrioxamine and mannitol on radical production and kidney function after ischaemia-reperfusion. A study on rabbit kidneys

The effects of pre-treatment with mannitol and the iron chelator desferrioxamine on oxygen radical formation and glomerular and tubular function after ischaemia in the rabbit kidney were studied. Radicals were measured with ESR and spin trapping. At reperfusion after 60 min of renal ischaemia there was a significant increase in the production of free radicals in the venous effluent from the kidney. Administration of either mannitol or desferrioxamine given before ischaemia and before recirculation reduced the radical production significantly. The iron chelator appeared to be more effective. Glomerular function measured 48 h after reperfusion was significantly better after pretreatment with desferrioxamine and mannitol compared with mannitol alone. Tubular function did not differ between the two pre-treatment groups.     

ESR-measurement of production of oxygen radicals in vivo before and after renal ischaemia in the rabbit

This study describes a spin trap technique to determine production of oxygen radicals in rabbit kidneys after ischaemia and reperfusion. OXANOH was infused intraarterially. When exposed to oxygen free radicals OXANOH is oxidized to the stable radical OXANO. The concentration of OXANO in samples of renal venous blood was determined by ESR. Production of oxygen radicals was calculated from the amount of OXANO in the venous blood and the blood flow which was determined by an ultrasound technique. The radical production at reperfusion after ischaemia was expressed as a per cent of the pre-ischaemic value. A drastic increase in radical production was observed during (60 min) reperfusion after 60 min of ischaemia. Pretreatment with oxypurinol (20 mg kg^-1) before ischaemia and before recirculation almost completely abolished the rise in radical production at recirculation. Similar results were obtained when oxypurinol was given before recirculation only.     

Use of α-tocopherol emulsion for antioxidant protection of ischemic or stored kidneys

The ability of α-tocopherol in the form of an emulsion to augment the antioxidant reserve of kidneys during their ischemia or storage is explored. Over 10 min after an intravenous injection of the emulsion into rats or rabbits at 10 mg/kg body weight, the mean α-tocopherol concentration in the renal cortical layer rose from 6.7±0.2 to 7.4±0.2 μg/g (p<0.05); the injection also slowed the accumulation of malonic dialdehyde in cortical layer homogenates of intact and ischemic kidneys during ascorbate-induced lipid peroxidation. In kidneys stored at 4°C in a preservative solution to which the α-tocopherol emulsion had been added (10 mg/liter), lipid peroxidation was found to be inhibited after 24 and 48 h of storage. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 499–502, May, 1996     

Quantification of tissue damage in the feline small intestine during ischaemia-reperfusion: the importance of free radicals

Intestinal ischaemia is accompanied by characteristic mucosal lesions, which can be graded according to a six-grade system proposed by Chiu et al. (1970). This report describes a continuous grading system which makes it possible to quantify the intestinal damage in connection with ischaemia-reperfusion. The present morphometric method is based on quantitative histological analysis of intestinal biopsies performed on 200 histological sections from 44 cat experiments. Radical formation was quantified by infusing close i.a. a spin trap, OXANOH, which produces a secondary stable radical, OXANO-, after reacting with radicals in the tissue. OXANO- concentration was determined in venous blood samples with electron spin resonance. We demonstrate a highly significant correlation between the grading system of Chiu et al. (1970) and the morphometric analysis of this study. The tissue damage was located exclusively in the intestinal villi. Comparing the mucosal damage that occurs during 60 min of intestinal ischaemia (superior mesenteric artery pressure 15–25 mmHg) with that seen during the first 30 min reperfusion this study shows that the villus damage occurring during ischaemia is at least twice as large as the aggravation seen upon reperfusion. Furthermore, the authors demonstrate a significant correlation between rate of radical formation and villus tissue damage particularly during the first 30 min after ischaemia. It is concluded that the proposed quantitative morphological method represents a non-discrete grading system for evaluating tissue damage in connection with ischaemia-reperfusion in the small intestine. The ischaemia itself inflicted a more severe damage to the intestine than reperfusion. A significant correlation between damage and radical formation was demonstrated during the reperfusion. However, the results suggest that factors other than radical formation are of importance in explaining the tissue damage upon reperfusion. The nature of these factors is presently unknown.     

The oxidant and antioxidant effects of 25-hydroxyvitamin D3 in liver, kidney and heart tissues of diabetic rats

Abstract Previous studies have implicated protective effects of vitamin D on insulin secretion and pancreas cell function. The goal of the present study is to determine if a combination therapy of 25-hydroxyvitamin D3 and insulin had any advantage over insulin therapy alone on lipid peroxidation and antioxidant activity in the streptozotocin (STZ)-induced diabetic rat. The lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS), was measured to assess free radical activity in the heart, kidney and liver tissues. The enzymatic activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were measured as indicators of antioxidation in these tissues. Sprague-Dawley rats were made diabetic with a single injection of STZ (75 mg/kg i.p.). Rats were separated into three groups, each containing 10 animals: Group 1, non-diabetic and no drug treatment was given; Group 2, diabetic rats were treated with 3 IU/day subcutaneous (s.c.) insulin; and Group 3, diabetic rats were treated with 3 IU/day (s.c.) insulin plus 1 mg/kg/day per oral (p.o.) 25-hydroxyvitamin D3 for a period of 4 weeks. At the end of the study, TBARS contents of the liver, kidney and heart tissues in Groups 2 and 3 were found to be significantly increased as compared to Group 1 (P<0.05) and kidney MDA levels in Group 3 were also significantly increased as compared to Group 2 (P<0.05). The SOD and CAT contents of the heart in Group 2 were significantly increased as compared to Groups 1 and 3 (P<0.05). GSH-Px activity was unaltered in all groups (P>0.05). We suggest that a combination of insulin with 25-hydroxyvitamin D3 treatment would not be more beneficial than the use of insulin alone in antioxidant defence of diabetic liver and kidney tissues.     

ESR-measurement of oxygen radicals in vivo after renal ischaemia in the rabbit. Effects of pre-treatment with superoxide dismutase and heparin

The effects of intracellular and extraceIlular superoxide dismutase and heparin administration on oxygen radical formation after ischaemia in the rabbit kidney were studied. Radicals were measured with ESR and spin trapping. At reperfusion after 60 min of renal ischaemia there was a significant increase in the production of free radicals in the venous effluent from the kidney. Administration of either intracellular superoxide dismutase or extracellular superoxide dismutase before ischaemia and before reperfusion prevented approximately 85 % of the radical formation seen in the untreated control group. Administration of heparin 5 min before recirculation resulted in a 65% decrease in radical production compared to the control group.     

The influence of angiotensin converting enzyme inhibitors on lipid peroxidation in sera and aorta of rabbits in diet-induced hypercholesterolemia

In hypercholesterolemia increased lipid and lipoprotein peroxidation occurs. The renin-angiotensin system plays an important role in atherogenesis. Angiotensin II induces smooth muscle cells proliferation and stimulates oxidation of LDL particles and foam cell accumulation. Inhibition of ang II production leads to decrease in lipid peroxide production. The aim of this study was to assess the lipid peroxidation expressed as concentration of thiobarbituric acid reactive species (TBARS) in sera and aorta homogenates after administration of two doses of angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril and quinapril) in diet-induced hypercholesterolemia in rabbits. Sixty-four New Zealand rabbits were used. Animals were fed with standard fodder, special diet (1% cholesterol content) or special diet + tested ACEI. Two doses of ACE inhibitors were used: i), equivalent to applied to humans, ii), dose 10 times higher. The animals were divided into 8 groups: control, standard fodder; B, special diet; C1, C2, special diet + captopril in doses 2.5 and 25 mg/kg/24 h, respectively; E1, E2, special diet + enalapril in doses 0.75 and 7.5 mg/kg/24 h, respectively; Q1 and Q2, special diet + quinapril in doses 0.75 and 7.5 mg/kg per day, respectively. In cholesterol-fed rabbits and in groups receiving lower doses of tested ACE inhibitors, the serum TBARS concentration at 6 months was significantly higher in comparison to the control. The higher doses of enalapril, quinapril and captopril, prevented the cholesterol-induced rise in TBARS concentration. Lower dose of captopril attenuated the rise in TBARS concentration, it was significantly lower in comparison to group B, but higher than in the control group. In animals from groups B, E1, C1, Q1 TBARS concentration in aortae was significantly higher as compared to control group. Both doses of captopril and higher doses of enalapril and quinapril inhibited the rise of lipid peroxides concentration induced by cholesterol-rich diet.     

ESR-measurement of production of oxygen radicals in vivo before and after renal ischaemia in the rabbit.

This study describes a spin trap technique to determine production of oxygen radicals in rabbit kidneys after ischaemia and reperfusion. OXANOH was infused intra-arterially. When exposed to oxygen free radicals OXANOH is oxidized to the stable radical OXANO(.). The concentration of OXANO. in samples of renal venous blood was determined by ESR. Production of oxygen radicals was calculated from the amount of OXANO. in the venous blood and the blood flow which was determined by an ultrasound technique. The radical production at reperfusion after ischaemia was expressed as a per cent of the pre-ischaemic value. A drastic increase in radical production was observed during (60 min) reperfusion after 60 min of ischaemia. Pretreatment with oxypurinol (20 mg kg-1) before ischaemia and before recirculation almost completely abolished the rise in radical production at recirculation. Similar results were obtained when oxypurinol was given before recirculation only.     

Changes in blood lipid peroxidation markers and antioxidants after a single sprint anaerobic exercise

It has been well demonstrated that the principal factor responsible for oxidative damage during exercise is the increase in oxygen consumption. However, other theoretical factors (acidosis, catecholamine autoxidation, ischemia-reperfusion syndrome, etc.) that are known to induce, in vitro, oxidative damage may also be operative during short-term supramaximal anaerobic exercise. Therefore, we hypothesized that short-term supramaximal anaerobic exercise (30-s Wingate test) could induce an oxidative stress. Lipid peroxidation markers [serum lipid radical production detected by electron spin resonance (ESR) spectroscopy and plasma malondialdehyde (MDA) levels detected by the thiobarbituric acid reactive substances (TBARS) method], as well as erythrocyte antioxidant enzyme activities [glutathione peroxidase (GPx), superoxide dismutase (SOD)] and erythrocyte glutathione (GSH) levels, were measured at rest, after the Wingate test and during the 40 min of recovery. The recovery of exercise was associated with a significant increase (x2.7) in lipid radical production detected by ESR spectroscopy, as well as with changes in the erythrocyte GSH level (−13.6%) and SOD activity (−11.7%). The paradoxical decrease in plasma TBARS (−23.7%) which was correlated with the peak power developed during the Wingate test (r=−0.7), strongly suggests that such exercise stimulates the elimination of MDA. In conclusion, this study demonstrates that short-term supramaximal anaerobic exercise induces an oxidative stress and that the plasma TBARS level is not a suitable marker during this type of exercise. Electronic Publication     

Generation of lipid radicals in the hippocampus of neonatal rats after acute hypoxic-ischemic brain damage

Free radical-mediated lipid peroxidation has been strongly suggested to be the main cause of neuronal toxicity in the rat brain, including neonatal brain damage. The primary objective of this experiment was to see if the generation of free radicals occurred in the acute phase of ischemic-hypoxic insult in neonatal rats, by electron paramagnetic resonance (EPR) spectroscopy and in vivo brain microdialysis. A spin trap agent, α-(4-pyridyl-N-oxide)-N-tert-butylnitrone was perfused through a probe in the hippocampus before and after hypoxia and then an analysis was performed by EPR. From the EPR analysis of spin adduct in the dialysates, we obtained the EPR spectrum of six line spectra for which the hyperfine coupling constants corresponded to those of the EPR signal from the lipoxygenase/linoleic acid (LPX/LA), a lipid radical generating system, increased transiently just after hypoxia. The results of our in vivo study show the lipid peroxidation of the neuronal membrane to progress during neonatal ischemic-hypoxic insult. We hypothesize that an increased formation of lipid radicals may participate in the cascade of reactions leading to neuronal damage in the hippocampus following ischemic-hypoxic insult in neonatal rats.     

Introduction of α-Tocopherol into Bovine Lymphocyte Surfaces by Lipid Vesicles: Effects of Phospholipid Composition on α-Tocopherol Transfer

Liposomes transferred α-tocopherol to bovine peripheral blood lymphocytes (BPBL) at 39°C. Phospholipid (?¹⁴C? DMPC) transferred into BPBL at rates similar to ?³H? α-tocopherol but with less efficiency than ?³H? α-tocopherol from liposomes containing both labels. Liposomes containing unsaturated phospholipids DOPC and DLPC reduced but did not stop the rates of transfer of a-T to BPBL when compared to liposomes composed of DMPC. The presence of ?¹⁴C? cholesterol in liposomes with ?³H? α-tocopherol does not restrict but possibly enhances the α-tocopherol transfer into BPBL.     

Lipid peroxidation in cats experimentally infected with <Emphasis Type="Italic">Trypanosoma evansi</Emphasis>

The objective of this study was to evaluate the lipid peroxidation and the susceptibility of erythrocytes to in vitro peroxidation as indicators of oxidative damage in erythrocytes and their roles in the pathogenesis of anemia during experimental Trypanosoma evansi infection in cats. Animals were divided into two groups: control and infected with T. evansi. Seven cats were infected with 10⁸ trypomastigotes each, and parasitemia was estimated daily for 49 days by microscopic examination of smears. Hematological and biochemical parameters were evaluated for monitoring of the disease. Plasma lipid peroxidation (Thiobarbituric Acid Reactive Substances (TBARS)) and the susceptibility of erythrocytes to in vitro peroxidation were evaluated. Blood samples for analysis were collected at days 21 and 49 post-inoculation. TBARS level, indicated by MDA concentration, was higher in the infected group than in the control group in both analyzed periods, as well as the in vitro erythrocyte peroxidation (P < 0.001). The infected cats had variable degrees of regenerative anemia, which could be explained by the damage in erythrocyte membrane caused by lipid peroxidation.     

Effect of combined supplementation with vitamin E and alpha‐lipoic acid on myocardial performance during in vivo ischaemia‐reperfusion

Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia‐reperfusion (I‐R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha‐lipoic acid (α‐LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I‐R. The purpose of these experiments was to investigate the effects of VE and α‐LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I‐R insult. Female Sprague–Dawley rats (4‐months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and α‐LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN‐93M standards, which contains 75 IU VE kg^–1 diet. The ANTIOXID diet contained 10 000 IU VE kg^–1 diet and 1.65 g α‐LA kg^–1 diet. After the 14‐week feeding period, significant differences (P < 0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I‐R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P > 0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I‐R protocol. Following I‐R, two markers of lipid peroxidation were lower (P < 0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and α‐LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in vivo I‐R in young adult rats.     

α-Tocopherol protected against cobalt nanoparticles and cocl2 induced cytotoxicity and inflammation in Balb/3T3 cells

Context: Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co²⁺) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it.

Objective: We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co²⁺ and developed strategies to reduce this cytotoxicity with α-tocopherol treatment.

Methods: To evaluate the protective effect of α-tocopherol, Balb/3T3 cells were pretreated with 10?μM α-tocopherol for 24?h. The cells were then exposed to different concentrations of CoNPs and Co²⁺ for 12?h, 24?h and 48?h. The cell viabilities, reactive oxygen species (ROS), inflammatory cytokines and MAP kinase (MAPK) levels were measured.

Results: CoNPs and Co²⁺ can induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, α-tocopherol pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co²⁺, decrease ROS production and decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK pathway may be involved in the protection of α-tocopherol against cytotoxicity induced by CoNPs and Co²⁺ in vitro.

Conclusions: Our results provide new insights into the potential therapeutic use of α-tocopherol in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.     

α-Tocopherol attenuates alcohol-induced cerebral vascular damage in rats: possible role of oxidants in alcohol brain pathology and stroke

Effects of chronic (14 day) pretreatment of timed-release of α-tocopherol (∼1.25–5 mg/day) on alcohol-induced venular cerebrovasospasm, microvessel rupture and micro-hemorrhaging was studied by direct, quantitative in-vivo high-resolution TV microscopy of the intact rat brain. Sham animals chronically treated with placebo exhibited concentration-dependent venular cerebrovasospasm, microvessel rupture and focal hemorrhages, irrespective of route (i.e. perivascular, systemic) of ethanol administration. α-Tocopherol pretreatment either prevented or ameliorated greatly the cerebrovasospasm and vascular damage induced by ethanol. These results suggest that alcohol-induced cerebral vascular and brain damage by reperfusion injury events triggers lipid peroxidation of vascular smooth muscle and endothelial cell membranes; these pro-oxidant events could play a crucial role in the pathogenesis of alcohol-induced cerebral ischemia and stroke.