Impact of calcineurin inhibitors on rat glioma cells viability / 영남의대학술지

BACKGROUND@#Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells.@*METHODS@#Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.@*RESULTS@#Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration.@*CONCLUSION@#CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.

Impact of calcineurin inhibitors on rat glioma cells viability / 영남의대학술지

BACKGROUND: Although kidney transplantation outcomes have improved dramatically after using calcineurin inhibitors (CNIs), CNI toxicity continues to be reported and the mechanism remains uncertain. Here, we investigated the neurotoxicity of CNIs by focusing on the viability of glioma cells.METHODS: Glioma cells were treated with several concentrations of CNIs for 24 hours at 37℃ and their cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.RESULTS: Exposure to 0, 0.25, 0.5, 2.5, 5.0, and 10.0 mM concentrations respectively showed 100%, 64.3%, 61.3%, 68.1%, 62.4%, and 68.6% cell viability for cyclosporine and 100%, 38.6%, 40.8%, 43.7%, 37.8%, and 43.0% for tacrolimus. The direct toxic effect of tacrolimus on glioma cell viability was stronger than that of cyclosporine at the same concentration.CONCLUSION: CNIs can cause neurological side effects by directly exerting cytotoxic effects on brain cells. Therefore, we should carefully monitor the neurologic symptoms and level of CNIs in kidney transplant patients.

Verification of learner’s differences by team-based learning in biochemistry classes / 한국의학교육

PURPOSE: We tested the effect of team-based learning (TBL) on medical education through the second-year premedical students’ TBL scores in biochemistry classes over 5 years. METHODS: We analyzed the results based on test scores before and after the students’ debate. The groups of students for statistical analysis were divided as follows: group 1 comprised the top-ranked students, group 3 comprised the low-ranked students, and group 2 comprised the medium-ranked students. Therefore, group T comprised 382 students (the total number of students in group 1, 2, and 3). To calibrate the difficulty of the test, original scores were converted into standardized scores. We determined the differences of the tests using Student t-test, and the relationship between scores before, and after the TBL using linear regression tests. RESULTS: Although there was a decrease in the lowest score, group T and 3 showed a significant increase in both original and standardized scores; there was also an increase in the standardized score of group 3. There was a positive correlation between the pre- and the post-debate scores in group T, and 2. And the beta values of the pre-debate scores and “the changes between the pre- and post-debate scores” were statistically significant in both original and standardized scores. CONCLUSION: TBL is one of the educational methods for helping students improve their grades, particularly those of low-ranked students.

Effect of Immunosuppressive Drugs on the Metalloproteinase in the Glioma Cells and Osteoblasts / 계명의대학술지

The matrix metalloproteinases (MMPs) play a key role in the normal physiology of connective tissue during development, morphogenesis, and wound healing. Dysregulation of their activity has been implicated in numerous diseases including encephalopathy and the process of bone loss. Thus, MMPs may play a role in the encephalopathy and post-transplantation bone disease by immunosuppressive drugs such as cyclosporine (CsA) and tacrolimus. Gelatin zymography of MMP-9 and MMP-2 was performed in the glioma cells and osteoblast after CsA or tacrolimus treatment. Glioma cells or rat osteoblast ROS17/2.8 cells were treated with CsA or tacrolimus to make final concentration from 2 to 250 µM. After incubation, gelatin zymography of MMP-9 and MMP-2 was performed. And the density for the MMP bands were measured using luminescent image analyzer system. Both MMP-9 and MMP-2 activities in the osteoblast cells were decreased depending on the concentration of CsA or tacrolimus. MMP-2 activity was increased after CsA or tacrolimus treatment in the glioma cells. However, MMP-9 activities were decreased after CsA or tacrolimus treatment in the glioma cells. These results indicate that dysregulation of MMPs in the osteoblast and in the glioma cells by immunosuppressive drugs may one of the contributing factors in post-transplantation bone disease and in the encephalopathy by tacrolimus or cyclosporine.

Effect of Amino Acids and Albumin on Damage Induced by Cyanate in Osteoblast / 대한신장학회지

PURPOSE: Cyanate, known as one of the uremic toxins and derived spontaneously from urea, has several effects on the biologic substances including erythropoietin, antioxidant and ceruloplasmin. To find out the protective materials from the hazardous effect of cyanate in osteoblast, we added twenty amino acids, albumin globulin and hemoglobin in the culture media containing osteoblastic cells with cyanate. METHODS: Osteoblastic ROS 17/2.8 cells, exposed to various concentrations of sodium cyanate, were used to analyze for the cytotoxicity. The cyanate-induced cytotoxicity was assessed by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay by measuring the absorbance of the reaction solution at 570 nm. Viability of the treated cells was expressed as A570 of sample/A570 of control. The degree of the carbamylation was measured using trinitrobenzenesulphonic acid. The degree of the carbamylation in amino acid was about 50% in average. RESULTS: The degree of the carbamylation in albumin was increased depending on the incubation time with cyanate and the concentration of the cyanate. The degree of the carbamylation in globulin and hemoglobin was nearly zero. Asp, Glu, Leu, Trp and Tyr among the twenty amino acids revealed the protective effect against the damage induced by cyanate. And only albumin among the three proteins revealed the protective effect. CONCLUSION: On the basis of these results, Asp, Glu, Leu, Trp, Tyr and albumin are useful tools for the protection against damages by cyanate carbamylation.

Antioxidant Status in Nonalcoholic Steatohepatitis / 대한간학회지

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is chronic liver disease that can potentially progress to end stage liver disease. Oxidative stress to the vulnerable fatty liver has been reported as a key mechanism in development of NASH. Several antioxidant pathways have been identified, but reports that involved quantitative analysis of each antioxidant systems are rare, and these reports have shown various results. So, we investigated antioxidant status and the degree of oxidative stress by measuring several antioxidant enzymes, the total antioxidant status (TAS), and the metabolites of superoxide in NASH patients. METHODS: Nineteen NASH patients who were confirmed by liver biopsy and fifteen controls were involved in this study. The levels of body mass index (BMI), AST, ALT, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, TAS, hydrogen peroxide (H2O2), and malondialdehyde (MDA) were compared between both groups. The relationship between the histologic severity and the levels of each antioxidants were analyzed in the NASH group. RESULTS: The activities of SOD and catalase were lower in the NASH group. The concentrations of TAS and H2O2 were higher in NASH group. The level of GPx and MDA showed no significant differences between both groups. There were no significant relationships between the above variables and the pathological severity. CONCLUSIONS: The disturbed metabolism of superoxide due to the decreased activities of SOD and catalase seem to be important in the pathogenesis of NASH. Further investigations about the nonenzymatic secondary antioxidant mechanism are necessary because the TAS was higher for the NASH group. The lack of difference between both groups for the concentration of MDA indicates that mechanisms other than lipid peroxidation also may be important in the pathogenesis of NASH.

Metabolism of Reactive Oxygen Species in Neutrophils from Patients with End-Stage Renal Disease / 대한신장학회잡지

BACKGROUND: The present study was aimed to know the cause of impaired bactericidal activity, especially the metabolism of oxygen free radicals in neutrophils from patients with end-stage renal disease (ESRD). METHODS: We measured the amount of superox ide anion, the activity of three antioxidant enzymes, myeloperoxidase, copper ion level, zinc ion level and the amount of malondialdehyde in neutrophils from patients with ESRD before and after hemodialysis. Reverse transcription-polymerase chain reaction (RT-PCR) for superoxide dismutase (SOD) was also done. RESULTS: The malondialdehyde level, the amount of superoxide anion, catalase, and myeloperoxidase levels in the neutrophils from the patients with ESRD were higher than those from healthy controls. SOD activity, hydrogen peroxide level and zinc level were lower in ESRD patients. On the RT-PCR, the relative index, which is defined the ratio of the band densities for SOD to glyceraldehyde 3-phosphate dehydrogenase, was decreased in neutrophils from patients with ESRD. Glutathione peroxidase activity in the neutrophils from ESRD patients did not show any significant change. CONCLUSION: These results indicate that there are some alterations in metabolism of oxygen free radicals including lower levels of hydrogen peroxide which exerting a direct germicidal ability, due to decreased gene expression and mineral levels. And these alterations might be one of the major mechanisms of impaired microbicidal activity in patients with ESRD.

Protective Effect of Melatonin on the Nephrotoxicity by Cisplatin / 대한신장학회잡지

BACKGROUND: Cisplatin (CP), an antitumor agent widely used in the treatment of cancers, has nephrotoxicity. This side effect is closely related to oxidative stress. In the present study, we attempted to reduce CP-induced nephrotoxicity in rats by administering melatonin, an antioxidant. METHODS: Male Sprague-Dawley rats were divided into different groups and were treated as follows: (1) saline control; (2) CP (16 mg/kg, i.p.); (3) CP plus melatonin (10 mg/kg, i.p.). The rats were sacrificed at the 6th day after CP treatment. To evaluate renal damage, BUN, serum creatinine, creatinine clearance and microscopic examination were done. Hydrogen peroxide which is one of the oxygen free radicals, and malondialdehyde which is known as a marker of the oxygen free radical mediated injury, and the activities of the antioxidant enzymes such as superoxied dismutase, catalase, and glutathione peroxidase were also measured. RESULTS: CP-treated rats showed the increase of BUN, serum creatinine, malondialdehyde, hydrogen peroxide and superoxide dismutase (SOD) in kidney. And CP-treated rats also showed the decrease of creatinine clearance and catalase levels. CP-treated rats showed severe tubular necrosis in proximal convoluted tubules under the light microscopic examination. The light microscopic finding and all of the parameters except SOD were restored in the rats injected with CP plus melatonin than those with CP alone. SOD level was higher in the rats injected with CP plus melatonin than that with CP alone. CONCIUSION: These results suggest that melatonin suppresses CP-induced nephrotoxicity by suppressing the production of reactive oxygen species via the activation of SOD and catalase.

The Effects of Coenzyme Q10, Kinetin, and Thioctic acid on Ultraviolet B Irradiated Cultured Human Skin Fibroblasts / 대한피부과학회지

BACKGROUND: Coenzyme Q10 is an endogenous lipid soluble antioxidant that scavenges reactive oxygen species (ROS) directly, inhibits biomolecule oxidation, and affects antioxidant defense in vivo. Kinetin (N6-furfuryladenine) belongs to the family of N6-substituted adenine derivatives known as cytokinins. Kinetin also exerts anti-aging effects. Commercial products of coenzyme Q10 and kinetin are developed and are selling as a rejuvenating drug. However, the action mechanisms of kinetin are not fully known, though it has been suggested to act both as an inhibitor of reactive oxygen species (ROS) formation and as a scavenger of ROS. Thioctic acid (alpha-Lipoic acid), which becomes a powerful antioxidant in its reduced form, has been suggested as a dietary supplement to treat diseases associated with excessive oxidant stress. Exposure of the skin to ultraviolet (UV) radiation, particulary UVB (290-320nm), causes adverse biological effects, including alterations in cutaneous immune cells, photoaging and photocarcinogenesis. Several studies have shown that coenzyme Q10, kinetin, and thioctic acid afforded the protection effects against UVB-induced inflammatory responses and photoaging. Objective and Method: In this study, we investigated the effects of coenzyme Q10, kinetin and thioctic acid on UVB irradiated human skin fibroblasts using a viability test, thiobarbituric acid assay and Northern blot analysis. RESULT: Cell survival curves after UVB irradiation showed a dose dependent decremental pattern by trypan blue exclusion assay. Only 30% of dermal fibroblasts survived at 150mJ/cm2 UVB irradiation. The damage was associated with cell membrane lipid peroxidation, as shown by accumulation malondialdehyde (MDA). By pre-cultivation with coenzyme Q10, kinetin and thioctic acid, a significant protection effect was noted as an increase in the absolute number of surviving cells and marked decrease in the levels of MDA. CONCLUSION: Coenzyme Q10, kinetin, and thioctic acid, which have been newly accepted as having UV protection properties, are effective membrane peroxidation inhibitors and inhibitors of reactive oxygen species (ROS) formation and scavenger of ROS.

Effect of Melatonin on the Cisplatin Induced Ototoxicity in Rats / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cisplatin (CP), an antitumor agent widely used in the treatment of head and neck cancers, has side effects such as ototoxicity and nephrotoxicity. These side effects are closely related to oxidative stress. In the present study, we attempted to suppress CP-induced ototoxicity in rats by administering melatonin, an antioxidant. MATERIALS AND METHOD: Male Sprague-Dawley rats were divided into different groups and were treated as follows: 1) saline control, 2) CP (16 mg/kg, i.p.), 3) CP plus melatonin (10 mg/kg, i.p.). The rats were sacrificed at the 6th day after CP treatment. RESULTS: CP-treated rats showed increase in cochlear malondialdehyde, hydrogen peroxide, glutathione peroxidase and glutathione reductase levels, and the decrease in cochlear superoxide dismutase (SOD) and catalase levels. CP-treated rats showed markedly decreased in the number of stereocilia on the inner hair cells and mildly decreased in the number of outer hair cells in organ of Corti under the light and scanning electron microscopic examination. Light and electron microscopic findings, and cochlear hydrogen peroxide, malondialdehyde, SOD, catalase, glutathione peroxidase and glutathione reductase levels were restored in the rats injected with CP plus melatonin than those with CP alone. CONCLUSION: These results suggest that melatonin suppresses CP-induced ototoxicity via the suppression of the increased production of reactive oxygen species.

Effect of Melatonin on Hemolysis Induced by Cyclosporine / 대한신장학회잡지

Hemolysis is one of the side effects of cyclosporine(CsA). Some experimental and clinical data have strongly suggested that CsA-induced hemolysis is resulted from the increased production of free radical species by CsA. Melatonin, a pineal secretory product, acts as a highly efficient free radical scavenger. Thus, melatonin may have a protective effect on the CsA-induced hemolysis. To test this hypothesis, the final concentration of 4.2x106/mL with human erythrocytes was incubated in test tube at 37 degrees C water bath with 1.67 mg/mL of CsA and 72 nmol/mL of melatonin. The degree of hemolysis and the amount of malondialdehyde which gives an indirect index of oxidative injury were measured in group 1 containing only isotonic buffer solution, in group 2 containing only CsA, and in group 3 containing both CsA and melatonin. The degrees of hemolysis in group 2 were higher than those of group 1. The degrees of hemolysis in group 3 were higher than those of group 1, and lower than those of group 2. The amounts of malondialdehyde in group 2 were higher than those of group 1. The amounts of malondialdehyde in group 3 were higher than those of group 1, and lower than those of group 2. These results indicate that the direct contact of erythrocytes with CsA results in free radical mediated hemolysis and the hemolysis by CsA can be prevented with melatonin.

Mechanism of Renal Oxidative Damage following 4-week Head-down Suspension in Rats

The purpose of this study was to observe the variation of malondialdehyde (MDA), an indirect index of oxidative damage, following 4-week of head-down suspension (HDS) at -45degreein rats as a model of simulated weightlessness. We also measured the activities of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase for clarifying the mechanisms of renal oxidative damage. MDA was increased (p<0.05) at the 4th week of HDS rats compared to control horizontal positioned rats. Following HDS, the renal activity of SOD was also significantly increased (p<0.01) at the 4th week of HDS whereas the changes of renal GSH-Px and catalase activities were not significantly different from controls. The expression of renal SOD mRNA used by polymerase-chain reaction method showed the similar pattern with the change of renal SOD activity and was more increased (p<0.05) than control horizontal positioned rat. These results indicate that simulated weightlessness induces the augmented SOD gene expression in the kidney which results in increased SOD activity, and thus increased production of MDA due to increased production of hydrogen peroxide. And under this condition, GSH-Px and catalase do not play their protective roles against hydrogen peroxide.

Effect of Cyanate on the Carbamylation and Biological Activity of Superoxide Dismutase / 대한신장학회잡지

The patients with end stage renal disease show several complications such as artherosclerosis, anemia and increased susceptibility to infection by damage due to oxygen free radicals. Superoxide dismutase(SOD) is directly linked to the fate of the highly reactive oxygen metabolites. If there is an alteration in the activity of SOD, this alteration may contribute to the complications by reactive oxygen species in patients with end stage renal disease. In this experiment, SOD activity and the effect of cyanate on the activity of SOD was studied to understand the mechanism of several complications mediated by oxygen free radicals in patients with end stage renal disease. SOD activity in the plasma and erythrocytes from patients with end stage renal disease was significantly lower than those from healthy controls. It is known that underproduction of SOD leads to excess production of superoxide and reduced iron favoring hydroxyl radical formation. The results in this experiment suggest that there is an overproduction of superoxide anion in patients with end stage renal disease. The overproduction of superoxide anion may contribute the patients with end stage renal disease susceptible to oxidant damages. To evaluate if cyanate could carbamylate SOD, SOD was incubated with cyanate. The level of carbamylated SOD increased as the time of exposure to cyanate increased from 0 hour to 72 hours. Furthermore, the degree of carbamylation of SOD increased as cyanate concentration in the incubation media rose from 20mM to 1M. There appears to be a maximum degree of carbamylation at a concentration of 1,000mM cyanate. To test the hypothesis that in vitro carbamylation of SOD alters its biological activity, SOD activity was measured after incubation with cyanate. The activity of carbamylated SOD decreased as the time of exposure to cyanate increased from 0 hour to 72 hours. Furthermore, the activity of carbamylated SOD decreased as cyanate concentration in the incubation media rose from 20mM to 1M and when albumin was added to the reaction mixture, the loss of SOD activity was prevented. These results are consistent with the hypothesis that SOD is also carbamylated and lost biological activity in end stage renal disease patients by cyanate, and that the degree of carbamylation depends on both the concentration of cyanate and the length of exposure. Also, these suggest that albumin may prevent carbamylation of SOD at least in vitro condition.

Effect of Cyanate on Lens Protein Carbamylation and Catalase Activuty

Proteins are known to be carbamylated as a result of reactions with ureaderived cyanate. We investigated the effect of carbamylation by cyanate on the catalase activity which is known that its decreased activity contributes to cataract formation, and on the lens protein. Catalase and lens protein were carbamylated by incubation with cyanate at 37degrees C. The extent of carbamylation was monitored by following the loss of free amino group using trinitrobenzenesulphonic acid. The level of carbamylated protein was 76% in patients with cataract. Carbamylated proteins in normal lens from rabbits and carbamylated catalase were increased as the time of exposure to cyanate activity. Our results suggest that cyanate is an inhibitor of catalase, and carbamylation of catalase as a result of reaction with ureaderived cyanate may contribute to cataract formation.

Effect of Cu Zn Levels on Superoxide Dismutase Activity in Erythrocytes from Patients with end Stage Renal Disease / 대한신장학회잡지

Suppressed superoxide dismutase activity, which is responsible for the dismutation of superoxide anion to hydrogen peroxide, is known to be one of the factors leading to lipid peroxidation in the erythrocyte membrane structures in the patients with end stage renal disease. In this study, copper and zinc levels were determined in the erythrocytes and plasma from 14 hemodialysis patients to explain the decreased activity of superoxide dismutase in erythrocytes. Before dialysis, superoxide dismutase, copper and zinc levels in erythrocytes were lower than those from healthy controls. Superoxide dismutase activity was normalized perfectly after hemodialysis. Copper level in the erythrocytes was normalized after hemodialysis, but its level was still lower than that in healthy controls. Zinc level in the erythrocytes was not changed after hemodialysis. Before hemodialysis, copper and zinc levels in plasma were higher than those from healthy controls. Copper level in the plasma was higher after hemodialysis than before hemodialysis. Zinc level in the plasma was not changed after hemodialysis. It is suggested that copper levels in erythrocytes from patients with hemodialysis affects partially to the superoxide dismutase activity, and superoxide dismutase activity is influenced more by copper levels than by zinc levels during hemodialysis.

Effect of Hemodialysis on Levels of Malondialdehyde and Antioxidant Enzymes in Erythrocytes from Patients with End Stage Renal Disease / 대한신장학회잡지

To clarify the mechanism of the protective effect of hemodialysis on lipid peroxidation in RBC membrane structures, the level of malondialdehyde (MDA) which is the lipid peroxidation product, and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) were determined before and after hemodialysis in the RBCs from 20 patients with end stage renal disease (ESRD), and from 14 healthy subjects. Before dialysis, MDA levels in the RBCs from the patients with ESRD were higher than those from healthy controls. SOD and catalase activities in the RBCs were lower. After hemodialysis, MDA, SOD, and catalase in the RBCs from the patients with ESRD were normalized. These results indicate that hemodialysis treatment is helpful to protect the peroxidative darnage through normalizing the activities of antioxidant enzymes.

Correlation between Levels of Serum Creatinine and Erythrocytic Malondialdehyde(MDA) and Antioxidant Enzymes in Patients with Diabetic Nephropathy / 대한신장학회잡지

Oxygen free radical activity is elevated in diabetes mellitus and has been implicated in the etiology of vascular complications and diabetic nephropathy is a serious microvascular complication in patients with IDDM. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and changes of peritubular microcirculation might deteriorate renal function in patients with IDDM. We performed this study to examine the oxidative stress and correlation between levels of serum creatinine and erythrocytic MDA, SOD, catalase, GPX in IDDM patients with diabetic nephropathy. Twenty one patients with IDDM(diabetic duration >5 years) and persistent albuminuria(albumin excretion>1000mg/day) and 15 normal healthy controls were investigated prospectively for erythrocytic MDA(thiobarbituric acid assay) and antioxidant enzymes[SOD(Hyland et al.), catalase(Nelson and Kiesow), GPX(Palgia and Valentine)] and correlation to serum creatinine levels. Levels of erythrocytic MDA were significantly higher in patients with diabetic nephropathy than in normal healthy controls(p0.05) and group 2(r=0.12,p>0.05) but there was significant correlation between serum levels of creatine and erythrocytic MDA in group 3(r=0.96, p0.05). We concluded that increased oxidative stress and decreased antioxidative defense mechanism might be factors in the initiation of diabetic nephropathy and the oxidative stress correlated with higher serum levels of creatinine(more than 5mg/dL)(p<0.05).

Activities of Hepatic Antioxidant Enzymes in Rats during 14 Days of Head-down Suspension as a Model of Simulated Weightlessness

Cells and tissues of human and animal are protected against free radicals by several complex mechanisms including the action of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase. There had been a few reports that simulated or actual weightlessness induced the decrease in activity of antioxidant enzymes and the increase in lipid peroxidation, The purpose of this study was to observe the time-course variation of antioxidant enzymes activities in rats during 14 days of head-down suspension(HDS) at -45 degrees as a model of simulated weightlessness. During HDS, the hepatic activity of SOD significantly decreased (p<0.05) at 3 day of HDS and then maintained a lower value compared to control horizontal position, GSH-Px activity also significantly decreased (p<0.05) at 3 and 7 day of HDS, thereafter showed a slight increasing trend to control horizontal value. The activity of hepatic catalase increased during HDS and the value at the end of HDS showed significant increase (p<0.05). From these results, there is a possibility that weightlessness induce the increase of oxygen free radicals according to the decrease of some antioxidant enzyme activities. The main scavenger to oxygen free radicals is operated via catalase system in rats during HDS. Therefore, we suggest that it is necessary to administrate the antioxidants for protection of the body against oxygen free radicals during first 1 week after exposure of weightlessness, at least.

Changes of Catecholamine Metabolic Enzymes in Rat Liver during 2 Weeks of Head-down Suspension

During simulated weightlessness and spaceflight, variations in plasma and urinary catecholamine(GA) levels haute been observed. The alterations of metabolism of CA In liver, the main site of metabolism, ate yet not known We measured the activity of catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO) In rat liver as Indicators of CA metabolism before and during head-down suspension The rats were placed In a -45 degress antiorthostatic position for 2 weeks. Head-down suspension resulted In decrease other hepatic MAO B activity By contrast, the activities of other hepatic degrading enzymes, COMT and MAO A, did not altered These findings Indicate that a prolonged exposure to simulated weightlessness exerts no remarkable effect on CA degradation in rat liver.

The protective effect of allopurinol on cholestatic liver injury induced by bile duct ligation

To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.