Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT03226 (vitamin E)
 17,558 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial protection by the water-soluble vitamin E analogue, Trolox, was investigated in 18 regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally ligated for 45 min and was reperfused for three days. Five grams of Trolox (n = 9) were infused intravenously before coronary occlusion. Treatment was continued with an intravenous dose of 5 grams Trolox/24 hours until the end of the experiment. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Generation of free radicals by stimulated neutrophils was evaluated by luminol-enhanced chemiluminescence. Plasma concentrations of Trolox were measured by high-performance liquid chromatography. Aside from heart rate before ischemia, global hemodynamic values including calculated left ventricular oxygen consumption did not differ significantly between the two groups. Plasma concentrations of Trolox measured 1.8 +/- 0.3 mmol/l (before ischemia), 0.96 +/- 0.13 mmol/l (before reperfusion), 0.77 +/- 0.1 mmol/l (40 min of reperfusion), and 0.08 mmol/l (end of the experiment). Generation of free radicals by stimulated neutrophils was reduced by about 30% in the treatment group before ischemia and immediately before reperfusion, but was not reduced at the end of the experiment. Risk regions (control group 19.4 +/- 6 g, treatment group 19.3 +/- 7 g) and infarct sizes (control group 69.3 +/- 8%, treatment group 69.3 +/- 12%) were almost identical. Regional systolic shortening of a control segment and of the risk region were similar in both groups before ischemia, before reperfusion, and after 45 min of reperfusion. After 3 days of reperfusion, regional systolic shortening of the reperfused myocardium of the treated group had recovered to a significantly greater extent (P = 0.027). This parameter amounted to 9 +/- 6% in the treated group and to 3 +/- 3% in the control group. Improved functional recovery was not accompanied by higher tissue concentrations of adenosine triphosphate. It is concluded that the chosen treatment with Trolox does not reduce infarct size but accelerates functional recovery. This finding suggests that the mechanisms resulting in myocardial necrosis during ischemia/reperfusion and in post-ischemic myocardial dysfunction may differ.
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PMID:The effects of Trolox, a water-soluble vitamin E analogue, in regionally ischemic, reperfused porcine hearts. 179 Oct 83

Preexisting magnesium deficiency may alter the susceptibility of rat hearts to postischemic oxidative injury (free radicals). This was examined in rats maintained for 3 weeks on a magnesium-deficient (Mg-D) diet with or without concurrent vitamin E treatment (1.2 mg/day, SC). Magnesium-sufficient (Mg-S) rats received the same diet supplemented with 100 mmol Mg/kg feed. Following sacrifice, isolated working hearts were subjected to 30-, 40-, or 60-min global ischemia and 30-min reperfusion. Postischemic production of free radicals was monitored using electron spin resonance (ESR) spectroscopy and spin trapping with alpha-phenyl-N-tert butylnitrone (PBN, 3 mM final); preischemic and postischemic effluent samples were collected and then extracted with toluene. PBN/alkoxyl adduct(s) (PBN/RO.; alpha H = 1.93 G, alpha N = 13.63 G) were the dominant signals detected in untreated Mg-S and Mg-D postischemic hearts, with comparably higher signal intensities observed for the Mg-D group following any ischemic duration. Time courses of postischemic PBN/RO. detection were biphasic for both groups (maxima: 2-4 and 8.5-12.5 min), and linear relationships between the extent of PBN/RO. production and the severity of both mechanical dysfunction and tissue injury were determined. Following each duration of ischemia, Mg-D hearts displayed greater levels of total PBN adduct production (1.7-2.0 times higher) and lower recovery of cardiac function (42-48% less) than Mg-S hearts. Pretreating Mg-D rats with vitamin E prior to imposing 40-min ischemia/reperfusion, led to a 49% reduction in total PBN/RO. production, a 55% lower LDH release and a 2.2-fold improvement in functional recovery, compared to untreated Mg-D hearts. These data suggest that magnesium deficiency predisposes postischemic hearts to enhanced oxidative injury and functional loss, and that antioxidants may offer significant protection against the pro-oxidant influence(s) of magnesium deficiency.
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PMID:Magnesium-deficiency potentiates free radical production associated with postischemic injury to rat hearts: vitamin E affords protection. 807 Jun 74

Effects of dietary vitamin E supplementation in rats were studied to determine whether or not they have a higher tolerance against cardiac ischemia-reperfusion injury using the working or Langendorff heart systems. Also, dihydrolipoic acid, recently reported to have potent antioxidant properties and accelerate vitamin E recycling of membrane in vitro, was perfused into the heart model systems to investigate its in vivo relationship with vitamin E. Tissue vitamin E content was increased by vitamin E feeding, but heart preparations did not show any improved functional recovery. Control hearts perfused with dihydrolipoic acid also did not show any improvement. However, a synergistic response is observed with the combination of dihydrolipoic acid perfusion and high dietary vitamin E using both perfusion systems in improvement of cardiac recovery. These results indicate that a high concentration of myocardial vitamin E does not increase tolerance to ischemia-reperfusion injury by itself, but, the combination of exogenous dihydrolipoic acid and high endogenous vitamin E can produce synergistic protective effects on recovery from ischemia during reperfusion.
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PMID:Cardiac recovery during post-ischemic reperfusion is improved by combination of vitamin E with dihydrolipoic acid. 825 Aug 67

The combination of vitamin E supplementation with dihydrolipoic acid perfusion synergistically improves cardiac functional recovery during post-ischemic reperfusion or post-hypoxic reoxygenation of the rat heart. To elucidate the mechanism of this effect, isolated rat hearts were perfused using a working heart system. In hearts perfused with a buffer containing dihydrolipoic acid, ATP levels were significantly higher than those of hearts perfused without addition of dihydrolipoic acid during 90 min of reoxygenation following 30 min of hypoxia. Cardiac tissue glutathione status measured in hearts after perfusion experiments showed significant elevation of reduced glutathione in vitamin E supplemented normoxic rat hearts without hypoxia. Significant elevation of oxidized glutathione was observed in dihydrolipoic acid perfused heart after hypoxia-reoxygenation. It is concluded that vitamin E and dihydrolipoic acid exert separate and synergistic effects in the protection of the hypoxic-reoxygenated heart.
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PMID:The influence of vitamin E and dihydrolipoic acid on cardiac energy and glutathione status under hypoxia-reoxygenation. 859

Lipid peroxidation contributes to myocardial reperfusion injury. The indenoindole H290/51, a lipid peroxidation inhibitor with balanced lipophilicity and a considerably higher antioxidative capacity than that of vitamin E, was tested for its myocardioprotective effect against reperfusion injury. Coronary-ligated pigs were subjected to 45 min of myocardial ischemia followed by 240 min of reperfusion. Starting five minutes prior to reperfusion, H290/51 (n = 6) or vehicle (n = 6) was retrogradely infused via a coronary vein for 30 min. The total dose of H290/51 was 1 microM in 300 ml fluid (10 ml/min). In addition to the hemodynamics, left ventricular (LV) wall segment shortening (%SS) was measured by sonomicrometry. The LV area at risk and infarct size were measured by means of Evans blue and triphenyl tetrazolium chloride staining. The hemodynamics did not change significantly during the study, and no differences were found between the two groups. In the H 290/51-treated pigs, %SS of the ischemic area recovered from 1.9% at the end of ischemia to 9.1% after 120 min (p < .05) and to 16.2% at 240 min (p < .01). There was no significant recovery in the vehicle group. The LV area at risk was approximately 20% of LV. Infarct size as a percentage of LV and of the area at risk was significantly smaller in the H290/51 group (9+/-3% and 46+/-11%) than in the control group (18+/-6%; p < .05 and 83+/-5%; p < .01). H290/51 effectively protected the myocardium at risk in the setting of myocardial ischemia followed by reperfusion. This effect was reflected by diminished infarct size and improved functional recovery.
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PMID:The lipid peroxidation inhibitor indenoindole H290/51 protects myocardium at risk of injury induced by ischemia-reperfusion. 958 2

Post-ischemic reperfusion causes cardiac dysfunction and radical-induced lipid peroxidation (LPO) detectable by ESR spin trapping. This study deals with the applicability of the spin trapping technique to pharmacological investigations during myocardial reperfusion injury. The use of the spin trap phenylbutylnitrone (PBN, 3 mM) in isolated rat hearts demonstrated the release of alkoxyl radicals (aN = 1.39 mT, aHbeta = 0.19 mT) formed particularly within the first 15 min of reperfusion following 30 min of ischemia. The decline of radicals, after 10 min of reperfusion, was accompanied by recovery of function in 80% of the hearts. The radical concentration in the coronary effluent (maximum after 7.5 min) was reduced by the infusion of 1 mM mercaptopropionylglycine (MPG, 2.7+/-0.5 U/ml, p < 0.001) or 5 microM vitamin E (11.7+/-0.8 U/ml, p < 0.001), compared to the (PBN-containing) control (29.7+/-4.3 U/ml). Moreover, functional recovery (left ventricular developed pressure, LVDP 91.6 +/-20% of pre-ischemic level, p < 0.05) was improved by the hydrophilic radical scavenger MPG, compared to the (PBN-containing) control (LVDP 50.5+/-15.7% of baseline). PBN alone led to higher functional recovery (p < 0.05) and reduced VF (duration of ventricular fibrillation; 7.10+/-0.36 min/30 min, p < 0.05), compared to the untreated (PBN-free) control (LVDP 26.6+/-11.8%; VF 19.42+/-3.64 min/30 min). The Ca antagonist verapamil (0.1 microM), MPG, and the lipophilic vitamin E showed cardioprotection in the absence of PBN: post-ischemic recovery of LVDP was 25.4+/-6.8% (p < 0.05), 39.6+/-12.7% (p < 0.05) and 52.4+/-2.6% (p < 0.01), respectively, compared to the corresponding untreated control (13.3+/-6.6%). Whereas verapamil and vitamin E were able to protect the heart when present alone, they offered no additive effect in the presence of PBN. Therefore, PBN can be used to estimate the radical scavenger properties of an agent in the heart. However, because of the protective properties of PBN itself, the results of simultaneous investigations of the effects of other compounds, such as Ca antagonists or lipophilic radical scavengers, on heart function may be limited.
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PMID:PBN spin trapping of free radicals in the reperfusion-injured heart. Limitations for pharmacological investigations. 977 91

Extensive biochemical data document the involvement of oxygen derived free radicals (ODFR) in recovery following neurotrauma as well as diabetic neuropathy. Vitamin E is considered as one of the principle protective mechanism against oxidative damage in neuronal tissue. The present study was undertaken to determine the association between functional recovery and vitamin E levels following sciatic nerve crush injury in normal and diabetic rats. The sciatic nerve of normal and streptozotocin (STZ) induced diabetic rats was crushed using a haemostat. The walking track analysis and vitamin E levels were recorded on 10, 20 and 30th day. Maximum functional deficiency and depletion of vitamin E in sciatic nerve was observed on 10th day following crush injury in both normal and diabetic animals. A progressive motor recovery and repletion of vitamin E was observed on day 20 and 30 following injury in both diabetic and normal rats. The functional recovery was slower whereas vitamin E level was higher in diabetic animals as compared to normal injured rats during healing phase suggesting that vitamin E alone may not be an efficient indicator of oxidative stress during regeneration of axons following trauma in diabetic rats.
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PMID:Functional recovery and vitamin E level following sciatic nerve crush injury in normal and diabetic rats. 1006 24

The rat heart protection offered by vitamin E against oxidative stress after ischaemia-reperfusion was studied by using a new methodological approach. Functional recovery of hearts from ischaemia-reperfusion was correlated with a traditional index of oxidative stress such as lipid peroxidation and with antioxidant capacity and susceptibility to oxidants of the tissue evaluated by enhanced chemiluminescence techniques. Rats were treated with ten daily i.m. injections of 100 mg/kg body weight of vitamin E. The functional recovery during reperfusion (20 min, following 45 min ischaemia) of Langendorff preparations from control (vehicle-injected) and vitamin E treated rats was evaluated in terms of heart rate, left ventricular developed pressure (LVDP), double product (= heart rate. LVDP) and coronary flow recovery. Vitamin E treatment significantly improved functional recovery of heart rate, LVDP, double product and coronary flow. It also increased the level of vitamin E and reduced the levels of both malondialdehyde and hydroperoxides in the heart tissue at the end of the ischaemia-reperfusion protocol. In contrast, it did not affect the antioxidant capacity and the response of heart homogenates to in vitro oxidative stress measured after ischaemia-reperfusion. These results show a protective action of vitamin E treatment against lipid peroxidation and cardiac dysfunction associated with ischaemia-reperfusion. Although the precise mechanism of this protection is not evident, our model in part suggests a role of vitamin E other than as a free radical scavenger.
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PMID:Protection against ischemia-reperfusion induced oxidative stress by vitamin E treatment. 1045 56

Hyperthyroidism has been reported to decrease heart antioxidant capacity and increase its susceptibility to in vitro oxidative stress. This may affect the heart response to ischemia-reperfusion, a condition that increases free radical production. We compared the functional recovery from in vitro ischemia-reperfusion (Langendorff) of hearts from euthyroid (E), hyperthyroid (H, ten daily intraperitoneal injections of T3, 10 microg/100g body weight), vitamin E-treated (VE, ten daily intramuscular injections, 20 mg/100g body weight) and hyperthyroid vitamin E-treated (HVE) rats. We also determined lipid peroxidation, tissue antioxidant capacity and the tissue capability to face an oxidative stress in vitro. A significant tachycardia was displayed during reperfusion following 20 min ischemia by the hyperthyroid hearts, together with a low recovery of left ventricular developed pressure (LVDP) and left ventricular dP/dt(max). When H hearts were paced at 300 beats/min, the functional recovery (LVDP and dP/dt(max)) was close to 100% and significantly higher than in E paced hearts. At the end of the ischemia-reperfusion protocol, myocardium antioxidant capacity was significantly lower, whereas lipid peroxidation and the susceptibility to in vitro oxidative stress were higher in the T3 treated (H) than in euthyroid rats. The in vitro tachycardic response, the reduction in the antioxidant capacity and the increase in lipid peroxidation were prevented by treatment of hyperthyroid rats with vitamin E (HVE). These results suggest that the tachycardic response to reperfusion following chronic T3 pretreatment was associated with the reduced capability of the heart to face oxidative stresses in hyperthyroidism.
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PMID:Effect of vitamin E on the response to ischemia-reperfusion of Langendorff heart preparations from hyperthyroid rats. 1068 May 78

The effects of low-intensity, prolonged swimming on functional recovery of the rat heart (Langendorff preparations) from ischaemia-reperfusion (I/R) were investigated. Three groups of rats (120 days old) were used: sedentary rats (S) and rats exercised by a single bout of swimming lasting 5 (E5) or 8 h (E8), respectively. The effect of exercise on the response to I/R was related to an index of oxidative damage such as lipid peroxidation, as well as to the tissue antioxidant capacity and the response of heart tissue to in vitro oxidative stress. The intrinsic performance of E5 Langendorff preparations paced at 220 beats x min(-1) was also determined. A group of sedentary animals was used for H2O2-treated preparations. The effect of antioxidant treatment on inotropic recovery during reperfusion was studied on preparations from 5 or 8 h swimming vitamin E-treated (EVT5 and EVT8 and 5 or 8 h swimming untreated (EVU5 and EVU8) rats. Hearts from exercised animals displayed a reduced preischaemic inotropism, which in E5 rats was accompanied by an increase in the intrinsic heart rate. The lower intrinsic cardiac inotropism of E5 animals was confirmed in the paced preparations. The reduced contractility found in control hearts after addition of H2O2 to perfusion medium suggested that the low inotropism of E5 and E8 hearts was due to an exercise-induced increase in reactive oxygen species. Inotropic recovery during reperfusion was low in the S hearts, was significantly increased in the E5 hearts, and was again reduced to the S level in the E8 hearts. In the E8 hearts the indexes of cellular damage (LDH release) and oxidative stress increased, and antioxidant capacity decreased, while in E5 hearts there was no evidence of significant changes in such parameters. Performance and reperfusion recovery of hearts from 5 h swimming rats was not affected by vitamin E treatment, while those of hearts from 8 h swimming rats was the highest observed. We suggest that the higher inotropic recovery during reperfusion in the hearts from the E5 rats is related to the negative inotropic effect of exercise. The fall in recovery following the 8 h exercise was instead related to the increased oxidative stress.
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PMID:Effects of prolonged aerobic exercise on myocardial responses to ischaemia-reperfusion in the rat. 1142 51


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