Neuroprotective Effects of Ebselen on Experimental Spinal Cord Injury in Rats

Spinal cord injury (SCI) results in rapid and significant oxidative stress. This study was aimed to investigate the possible beneficial effects of Ebselen in comparison with Methylprednisolone in experimental SCI. Thirty six Wistar albino rats (200–250 g) were divided in to six groups; A (control), B (only laminectomy), C (Trauma; laminectomy + spinal trauma), D (Placebo group; laminectomy + spinal trauma + serum physiologic), E (Methylprednisolone group; laminectomy + spinal trauma + Methylprednisolone treated), F (Ebselen group; laminectomy + spinal trauma + Ebselen treated), containing 6 rats each. Spinal cord injury (SCI) was performed by placement of an aneurysm clip, extradurally at the level of T11–12. After this application, group A, B and C were not treated with any drug. Group D received 1 ml serum physiologic. Group E received 30 mg/kg Methylprednisolone and, Group F received 10 mg/kg Ebselen intraperitoneally (i.p.). Rats were neurologically examined 24 h after trauma and spinal cord tissue samples had been harvested for both biochemical and histopathological evaluation. All rats were paraplegic after SCI except the ones in group A and B. Neurological scores were not different in traumatized rats than that of non-traumatized ones. SCI significantly increased spinal cord tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities compared to control. Methylprednisolone and Ebselen treatment decreased tissue MDA and PC levels and prevented inhibition of the enzymes SOD, GSH-Px and CAT in the tissues. However, the best results were obtained with Ebselen. In groups C and D, the neurons of the spinal cord tissue became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in groups E and F were very well protected, but not as good as the control group. The number of neurons in the spinal cord tissues of the groups C and D were significantly less than the groups A, B, E and F. We concluded that the use of Ebselen treatment might have potential benefits in spinal cord tissue damage on clinical grounds.     

Persistence of hyperbaric oxygen-induced oxidative effects after exposure in rat brain cortex tissue

Hyperbaric oxygen (HBO) causes oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. Many studies have reported oxidative effects of HBO, but there is no comprehensive data about how long this effect persists. The aim of this study was to elucidate the duration of HBO-induced oxidative/antioxidant action. Male Sprague-Dawley rats were divided into 5 groups. Except for the controls, the animals were subjected to 100% oxygen for 2 h at 3 atm and differed from each other by the time to dissection after exposure that began at 30, 60, 90, or 120 min. Thiobarbituric acid-reactive substances (TBARS), as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity was determined in brain cortex tissue. Additionally, nitrite-nitrate (NO(x)) concentrations were measured. All measured parameters were found to be significantly increased 30 min after exposure. SOD and GSH-Px levels persisted at significantly high levels for 60 min. In conclusion, the oxidative effect of HBO was shown to persist only for 1 h. Further studies should be performed to elucidate the possible molecular interactions during this period.     

Exposure Time Related Oxidative Action of Hyperbaric Oxygen in Rat Brain

Hyperbaric oxygen (HBO) is known to cause oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. The present study was performed to elucidate the relation of HBO exposure time to its oxidative effects in rats’ brain cortex tissue. For this purpose, 49 rats were randomly divided into five groups. Except the control group, study groups were subjected to three atmospheres HBO for 30, 60, 90, and 120 min. Their cerebral cortex layer was taken immediately after exposure and used for analysis. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and nitrate–nitrite (NO_X) levels were determined. TBARS and SOD levels were found to increase in a time-dependent manner. GSH-Px activity reflected an inconsistent course. NO_X levels were found to be increased only in the 120 min exposed group. The results of this study suggests that HBO induced oxidative effects are strongly related with exposure time.     

Effects of Chronic Restraint Stress and 17-β-Estradiol Replacement on Oxidative Stress in the Spinal Cord of Ovariectomized Female Rats

Previous studies have shown sex-specific oxidative changes in spinal cord of rats submitted to chronic stress, which may be due to gonadal hormones. Here, we assessed total radical-trapping potential (TRAP), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and lipid peroxidation (evaluated by the TBARS test) in the spinal cord of ovariectomized (OVX) female rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided into controls and chronically stressed (for 40 days). Our findings demonstrate that chronic stress decreased TRAP, and increased SOD activity in spinal cord homogenates from ovariectomized female rats and had no effect on GPx activity. On the other hand, groups receiving 17β-estradiol replacement presented a decreased GPx activity, but no alteration in TRAP and in SOD activity. No differences in the TBARS test were found in any of the groups analyzed. In conclusion, our results support the idea that chronic stress induces an imbalance between SOD and GPx activities, additionally decreasing TRAP. Estradiol replacement did not reverse the effects of chronic stress, but induced a decrease in GPx activity. Therefore, estradiol replacement in ovariectomized chronically stressed rats could make the spinal cord more susceptible to oxidative injury.     

Effects of a Single Intravenous Glucocorticoid Dose on Biogenic Amine Levels in Cat Lumbar Spinal Cord

Abstract: The effects of a single large intravenous dose of methylprednisolone on the steady state levels of dopamine, norepinephrine, and 5-hydroxytryptamine in cat lumbar spinal cord, as a function of dose (15, 30, or 90 mg/kg) and time (1 or 24 h) after administration, were examined by high performance liquid chromatography with electrochemical detection. Methylprednisolone produced a dose-related increase in the levels of dopamine and 5-hydroxytryptamine, but not norepinephrine, measured at 1 h. The effect of the single glucocorticoid dose was biphasic, however, as measurement of the three amines at 24 h showed each to be depressed below the levels found in untreated animals. The possible mechanistic basis and the significance of these glucocorticoid effects are discussed.     

Cardioprotective effect of the alcoholic extract of Terminalia arjuna bark in an in vivo model of myocardial ischemic reperfusion injury

The present study was designed to investigate the effects of chronic administration of the alcoholic extract of Terminalia arjuna (TAAE) bark on isoproterenol induced myocardial injury. The TAAE was administered orally to Wistar albino rats (150-200 g) in three different doses, by gastric gavage [3.4 mg/kg: (T1), 6.75 mg/kg: (T2) and 9.75 mg/kg: (T3)] 6 days/week for 4 weeks. At the end of this period, all the animals, except the normal untreated rats that served as the control group, were administered isoproterenol (ISO) 85 mg/kg, S.C., for two consecutive days to induce in vivo myocardial injury. After 48 hours rats were anaesthetized with anaesthetic ether, then sacrificed and the hearts were harvested for biochemical and histological studies. A significant rise in myocardial thiobarbituric acid reactive substances (TBARS) and loss of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (suggestive of increased oxidative stress) occurred in the hearts subjected to in vivo myocardial ischemic reperfusion injury. The 6.75 mg/kg TAAE treatment group (baseline) shows a significant increase in myocardial TBARS as well as endogenous antioxidants (GSH, SOD, and catalase), but not in the other treatment groups. In in vivo ischemic reperfusion injury of the TAAE treated rats there was a significant decrease in TBARS in all the groups. In 6.75 mg/kg treatment group, a significant rise in the levels of GSH, SOD and catalase were observed, and it shows better recovery profile than the other groups subjected to in vivo ischemic reperfusion injury. In histological studies, all the groups, except the isoproterenol treated group, showed preserved myocardium. The present study demonstrates that the 6.75 mg/kg TAAE augments endogenous antioxidant compounds of the rat heart and also prevents the myocardium from isoproterenol induced myocardial ischemic reperfusion injury.     

Lipid peroxidation and activity of antioxidant enzymes in diabetic rats

We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis of diabetic complications. We therefore investigated the levels of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin (STZ)-induced diabetic rats. The animals were divided into two groups: control and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and liver, heart, pancreas, kidney and blood were collected for measurement of various biochemical parameters. Diabetes was associated with a significant increase in TBARS in pancreas, heart and blood. The activity of CAT increased in liver, heart and blood but decreased in kidney. GSH-Px activity increased in pancreas and kidney while SOD activity increased in liver, heart and pancreas. Our findings suggest that oxidative stress occurs in diabetic state and that oxidative damage to tissues may be a contributory factor in complications associated with diabetes.     

自噬在高压氧预处理预防脊髓缺血再灌注损伤中 的作用机制研究*

目的:研究自噬在高压氧预处理预防脊髓缺血再灌注损伤中的机制。方法:新生大鼠脊髓神经元原代培养,分为对照组(氧糖剥夺)和高压氧(HBO)预处理组。通过应用免疫组织化学、Western blot分析两组LC3-Ⅱ与凋亡相关分子Beclin-1,Bcl-2,Casp-ase-3的表达变化。结果:发现重复高压氧预处理对氧糖剥夺诱导原代培养的脊髓神经元损伤具有明显的保护作用。免疫组化和Western blot显示与对照组相比高压氧预处理显著增加脊髓神经元细胞Bcl-2的表达,降低Beclin-1,Caspase-3以及自噬的特异性标记蛋白LC3-Ⅱ的表达。氧糖剥夺后对照组与高压氧组相比,LDH释放量明显增多(P<0.05)。结论:HBO预处理通过调节自噬减轻缺血再灌注损伤,为HBO预处理神经保护提供一条新的作用机制。     

Exogenously administered and endogenously produced melatonin reduce hyperbaric oxygen-induced oxidative stress in rat lung

Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A known side effect of HBO is the production of reactive oxygen species. Many antioxidants such as vitamins C and E, riboflavin and selenium have been used successfully to scavenge the reactive oxygen species caused by HBO administration. In this study, we aimed to see if melatonin, a newly discovered antioxidant, has a protective effect against the overproduction of reactive oxygen species produced by HBO in rat lung tissue. Sixty male Sprague-Dawley rats were divided into 5 groups as follows: control, daytime HBO (3 ATA, 120 min), daytime HBO plus melatonin (10 mg/kg), nighttime HBO and nighttime HBO (under light exposure). The MDA, SOD and CAT levels of daytime and nighttime HBO (under light exposure) increased significantly. This significance was not found in the daytime HBO plus melatonin and nighttime HBO groups when compared with the control. In this study, HBO caused oxidant stress, and melatonin decreased the levels of MDA, SOD and CAT. Moreover, endogenous melatonin was found to be a more effective antioxidant than exogenous 10 mg/kg melatonin.     

Resveratrol,an antioxidant,protects spinal cord injury in rats by suppressing MAPK pathway

Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS)/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury. Spinal cord ischemia–reperfusion injury (IRI) was performed by the infrarenal abdominal aorta with mini aneurysm clip model. The expressions of iNOS and p38MAPK and the levels of biochemical parameters, including nitrite/nitrate, malondialdehyde (MDA), advanced oxidation products (AOPP), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in control and experimental groups. IRI-induced rats treated with 10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by improved biological parameters measured in spinal cord tissue homogenates. The resveratrol treatment significantly decreased the levels of plasma nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK in IRI-induced rats. Further, IRI-produced free radicals were reduced by resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant levels such as GSH, SOD and CAT. Taken together, administration of resveratrol protects the damage caused by spinal cord ischemia with potential mechanism of suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of oxidative stress due to IRI.     

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by d-galactose in rat liver

d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU?+?GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.     

Does Hypothermic Treatment Provide an Advantage After Spinal Cord Injury Until Surgery? An Experimental Study

We compared the effects of early and late stage hypothermia treatment after spinal cord injury. Five groups each consisting of seven rats were included in this study. In Group 1a (Clip applied-non-treatment group) and Group 1b (Clip applied-treated group) the spinal cords were harvested 1 h after the injury. In Group 2a (clip applied, non-treated group) and Group 2b (clip applied-treated group) the injured segments were harvested 24 h after injury. Group 3 was designed as the sham-operated group. The significantly lower levels of TBARS and GSH-Px in Group 2a, as compared with Group 1b suggests that the hypothermia was effective in the early stage of treatment (P < 0.05). In contrast, TBARS and GSH-Px levels were significantly increased at the 24 h timepoint following treatment (P < 0.05).Short-term systemic hypothermia reduces lipid peroxidation in the early stages after spinal cord injury. This beneficial effect disappears 24 h following systemic hypothermic treatment.     

Effect of Nrf2 signaling pathway on the improvement of intestinal epithelial barrier dysfunction by hyperbaric oxygen treatment after spinal cord injury

Disruption of the intestinal epithelial barrier following spinal cord injury (SCI) seriously affect long-term quality of life. Oxidative stress-induced epithelial cells’ injury contributes to the epithelial barrier dysfunction. Hyperbaric oxygen (HBO) treatment has been proved to alleviate SCI. However, it is unclear whether or not HBO treatment affects intestinal barrier function following SCI. In this study, our purpose was to explore the impact of HBO treatment on intestinal epithelial barrier function and underlying mechanisms following SCI. An SCI model was established in rats, and the rats received HBO treatment. Intestinal injury, mucosal permeability, intercellular junction proteins, and oxidative stress indicators were evaluated in our study. We found that HBO treatment significantly alleviated intestinal histological damage, reduced mucosal permeability, and markedly prevented bacterial translocation. Furthermore, HBO treatment significantly increased the expression of Claudin-1 and E-cadherin, inhibited intestinal tissue oxidative stress as demonstrated by upregulation of superoxide dismutase and glutathione, and HBO downregulated malondialdehyde. Mechanically, we demonstrated that HBO treatment ameliorated intestinal oxidative stress possibly through upregulating nuclear factor E2-related factor 2 (Nrf2) and its downstream targets, Heme oxygenase-1(HO-1), NADH-quinone oxidoreductase-1(NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC). These results suggested that HBO treatment triggered antioxidative effects against intestinal epithelial barrier dysfunction by promoting Nrf2 signaling pathway after SCI.     

Preconditioning with hyperbaric oxygen induces tolerance against oxidative injury via increased expression of heme oxygenase-1 in primary cultured spinal cord neurons

Hyperbaric oxygen (HBO) preconditioning can induce ischemic tolerance in the spinal cord. The effect can be attenuated by the administration of an oxygen free radical scavenger or by inhibition of antioxidant enzymes. However, the mechanism underlying HBO preconditioning of neurons against ischemic injury remains enigmatic. Therefore, in the present study primary cultured spinal cord neurons were treated with HBO and then subjected to a hydrogen peroxide (H(2)O(2)) insult. The results show that H(2)O(2) stimulation of the cultured spinal neurons caused severe DNA damage and decreased cell viability, and that these neurons were well protected against damage after a single exposure to HBO preconditioning (0.35 MPa, 98% O(2), 37 degrees C, 2 h). The protective effect started 4 h after pretreatment and lasted for at least 24 h. The cultured neurons after HBO treatment also exhibited increased heme oxygenase-1 (HO-1) expression at both the protein and mRNA levels, which paralleled the protective effect of HBO. Treatment with tin-mesoporphyrin IX (SnMP), a specific HO-1 inhibitor, before HBO pretreatment abolished the HBO-induced adaptive protection noted in the cultured spinal neurons. In conclusion, HBO preconditioning can protect primary cultured spinal cord neurons against oxidative stress, and the upregulation of HO-1 expression plays an essential role in HBO induced preconditioning effect.     

The effect of hyperbaric oxygen treatment on aspiration pneumonia

We have studied whether hyperbaric oxygen (HBO) prevents different pulmonary aspiration materials-induced lung injury in rats. The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250 to 300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + HBO treated, BIO + HBO treated, and HCl + HBO treated. Saline, BIO, HCl were injected into the lungs in a volume of 2 ml/kg. A total of seven HBO sessions were performed at 2,4 atm 100% oxygen for 90 min at 6-h intervals. Seven days later, rats were sacrificed, and both lungs in all groups were examined biochemically and histopathologically. Our findings show that HBO inhibits the inflammatory response reducing significantly (P < 0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonar aspiration significantly increased the tissue HP content, malondialdehyde (MDA) levels and decreased (P < 0.05) the antioxidant enzyme (SOD, GSH-Px) activities. HBO treatment significantly (P < 0.05) decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase, TUNEL and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with HBO therapy. It was concluded that HBO treatment might be beneficial in lung injury, therefore, shows potential for clinical use.     

The protective mechanisms of defibrotide on liver ischaemia-reperfusion injury

During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischaemia-reperfusion (I/R) injury and hepatic dysfunction. In this study the protective effect of defibrotide (DEF) was evaluated in a rat model of liver I/R injury. Four groups of rats were subjected to the following protocols: saline infusion without ischaemia, DEF infusion without ischaemia, DEF infusion with hepatic I/R, and saline infusion with hepatic I/R. After a midline laporatomy, liver ischaemia was induced by 45 min of portal occlusion. DEF 175 mg/kg(-1) was infused before ischaemia in 10 ml of saline. The same volume of saline was infused into the control animals. At the end of the 45-min reperfusion interval, the animals were sacrified. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were determined in haemolysates, and malondialdehyde (MDA) level in the liver tissue was measured. Tissue MDA levels were significantly higher in the I/R plus saline group compared to the sham operation control groups (p < 0.01 and p < 0.05, respectively). Tissue MDA levels decreased in the DEF plus I/R group compared to the I/R plus saline group (p < 0.05), but DEF could not reduce tissue lipid peroxidation to the levels of the control sham operation groups. SOD and GSH-Px enzyme activities were significantly higher in DEF-treated animals than in the other groups (p < 0.05). These results suggest that DEF protects liver against I/R injury by increasing the antioxidant enzyme levels.     

Oxidative Stress Parameters in Different Brain Structures Following Lateral Fluid Percussion Injury in the Rat

Free radicals mediated damage of phospholipids, proteins and nucleic acids results in subsequent neuronal degeneration and cell loss. Aim of this study was to evaluate the existence of lipid and protein oxidative damage and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in various rat brain structures 24 h after lateral fluid percussion brain injury (LFPI). Parietal cortex, hippocampus, thalamus, entorhinal cortex, and cerebellum from the ipsilateral hemisphere were processed for analyses of the thiobarbituric acid reactive substances (TBARS) and oxidized protein levels as well as for the SOD and GSH-Px activities. Immunohistochemical detection of oxidized proteins was also performed. Results of our study showed that LFPI caused significant oxidative stress in the parietal cortex and hippocampus while other brain regions tested in this study were not oxidatively altered by LFPI. GSH-Px activities were significantly increased in the parietal cortex and hippocampus, while the SOD activities remained unchanged following LFPI in all regions investigated.     

Effects of repeated desflurane and sevoflurane anesthesia on enzymatic free radical scavanger system

Background: To investigate the possible effects of repeated sevoflurane and desflurane anesthesia on hepatocellular system by evaluating the free radical metabolism, hepatocellular enzymes and histopatholgical changes in rats. Methods: Four groups of animals were studied. Sevoflurane 2% (v/v) and desflurane 6% (v/v) in air/O₂ were administered to animals in group II (n = 9) and III (n = 9) respectively. 100% (v/v) O₂ was administered in group IV (n = 9). Administration was done for 60 minutes over 3 days. Nine animals were allocated to control group (group I), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), glutathione-s-transferase (GST) and thiobarbituric acid reactive substances (TBARS) were studied. Also electron microscopy was performed. Results: Catalase, SOD, GSH-Px, GST activities and TBARS levels were significantly higher in groups II and III than in group I (p < 0.05). All parameters were significantly higher in groups II versus group IV (p < 0.05). On the other hand, SOD, GSH-Px and GST activities were significantly elevated in group III than IV, but CAT activity and TBARS levels were not significantly. Catalase, SOD, GSH-Px, GST but not TBARS levels were significantly higher in groups II and III than in group IV (p < 0.05). TBARS levels were higher in group III than in group IV, but this elevation was not statistically significant. CAT, SOD and GSH-Px activities were significantly higher in groups II than in group III (p < 0.05). Conclusion: Although electron microscopy findings were similar for group II and III, we can conclude that sevoflurane might cause more cellular damage than desflurane by causing higher activation of free radical metabolising enzymes.     

Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.     

Effect of BQ-123 and nitric oxide inhibition on liver in rats after renal ischemia-reperfusion injury

Ischemia-reperfusion (I/R) injury induces an inflammatory response and production of oxygen-derived reactive species which affect many organs including heart, brain, kidney and gastrointestinal tract. The aim of this study was to assess the hepatic changes after renal I/R injury. Male Sprague Dawley rats were subjected to either sham operation or treatment with L-NAME, L-arginine and BQ-123 during 30 min renal ischemia and 2 h reperfusion injury. Hepatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) activities, and thiobarbituric acid-reactive substances (TBARS) and nitric oxide (NO) levels were evaluated to show hepatic response to renal I/R injury. Catalase and SOD activities showed significant differences between the control and the other groups after I/R. On the other hand, GSH-Px activity did not show any significant changes between the control and the other experimental groups mentioned under above conditions. Meanwhile, levels of TBARS were not different between the control and the other experimental groups, whereas NO level showed changes between the control and experimental groups except the one to which endothelin receptor antagonist agent (BQ-123) subjected. Experimental period may not be enough to determine the changes in GSH-Px activity and level of TBARS. However, catalase and SOD activities decreased in experimental groups treated by chemical agents. NO level decreased in chemicalagent-applied experimental groups but not in the group to which endothelin receptor antagonist BQ-123 was applied alone.