Evaluation of cardiovascular risk in children with solitary functioning kidney.

BACKGROUND: The present study investigates cardiovascular risk and kidney damage in patients with solitary kidneys. METHODS: Included in the study were 40 children with a unilateral functioning kidney and 60 healthy controls, all of whom were evaluated for carotid intima-media thickness, ischemia-modified albumin and oxidative stress parameters, and 24-h ambulatory blood pressure monitoring. RESULTS: Serum creatinine and urine microalbumin levels were higher and creatinine clearance was lower in the patient group than in the control group, and serum ischemia-modified albumin, carotid intima-media thickness, aldosterone, plasma renin activity and blood pressure were all higher in the patient group than in the control group. In addition, the patient group was showed a non-dipper pattern. CONCLUSION: Children with a normal functioning solitary kidney are likely at higher risk of developing cardiovascular disease and such patients should be followed closely before marked kidney impairment occurs.

The effect of fucoidin on kidney and lung injury in a rat infrarenal aortic ischemia-reperfusion model.

BACKGROUND: The aim of this study was to investigate the effects of fucoidin on rat kidney and lung in an infraaortic ishemia reperfusion model. METHODS: Forty Wistar rats were randomly divided into five groups (n = 8) as sham, control (IR), before ischemia (BI), before reperfusion (BR), and before ischemia and before reperfusion (BI/BR). Rats were subjected to 120 minutes ischemia followed by 120 minutes reperfusion with application of infrarenal aortic clamping. BI received intravenous fucoidin (25 mg/kg) ten minutes before establishing ischemia and BR received ten minutes before reperfusion. BI/BR group received half equal doses of fucoidin both before ischemia (12.5 mg/kg) and reperfusion (12.5 mg/kg) periods, respectively. After sacrification blood and tissue samples were obtained for biochemical (Malondialdehyde (MDA), Nitric oxide (NO), Myeloperoxidase (MPO), Catalase (CAT), Plasma Chitotriosidase (CHIT) and serum ischemia modified albumin (IMA)) and histologic examinations. RESULTS: MDA, NO, MPO, CAT, and IMA levels were lower in BR and BI/BR groups compared to control group (p < 0.001). Plasma CHIT levels in BR and BI/BR groups were lower than in control group (p < 0.05). According to histological examination kidney and lung injury scores were lower in BR and BI/BR groups compared to control group (p < 0.01 and p < 0.001, respectively). CONCLUSION: The study showed that fucoidin is effective in preventing kidney and lung injury if administered before reperfusion or both before ischemia and reperfusion. However, it has no effect if administered only before ischemia.

In vivo effects of Viscum album and probiotics against carbon tetrachloride-induced liver injury.

This study tested the possible protective and therapeutic effects of Viscum album extract and probiotics against carbon tetrachloride (CCl4)-induced acute/chronic liver injury. Male Wistar rats were assigned to seven groups: Control, acute CCl4, acute V. album + CCl4, acute V. album + Probiotics + CCl4, chronic CCl4, chronic CCl4 + V. album, and chronic CCl4 + V. album + Probiotics. Acute and chronic liver injuries were induced by 2 mg/kg CCl4 (i.p.) and 1 mg/kg CCl4 (i.p.), respectively. The extract and probiotics were administered daily to related groups. Serum enzyme activities, lipid profile, total protein, albumin, bilirubin, heme oxgenase-1 and 8-hydroxydeoxyguanosine levels were measured. Liver tissue sections stained with Hematoxylin-Eosin. Acute or chronic CCl4-exposure caused to significant changes in concentrations/activities of the measured parameters. The oral administration of extract and probiotics showed protective and therapeutic effects against CCl4-induced liver-injury. The supplementation of intestinal flora by the use of probiotics may enhance the efficacy of orally given therapeutic extracts.

Effects of N-nitro L-arginine methyl ester and α-tocopherol on testicular oxidative stress caused by exposure to cigarette smoke.

Testis is a rich organ with blood vessels. For this reason, it is possible that the toxic substances of the cigarette carried in the blood change the balance between the oxidant and the antioxidant system in this organ. In this study, it was aimed to investigate the effects of N-nitro L-arginine methyl ester and α-tocopherol on testicular oxidative stress caused by exposure to cigarette smoke. 45 wistar male rats were used in the study. Five groups were formed: control, cigarette smoke, cigarette smoke + α-tocopherol, cigarette smoke + N-nitro L-arginine methyl ester and cigarette smoke + α-tocopherol + N-nitro L-arginine methyl ester. Biochemical and histological evaluations were performed to determine the damage caused by cigarette smoke. It was observed that there were structural and functional disturbances at the cellular and hormonal level in the smoking group. Biochemical evaluations showed that cellular damage was reduced in treatment groups. Histological examinations were revealed that the damage caused by cigarette smoke exposure was eliminated in treatment groups. As a result of our study, we think that oxidative damage and hormonal irregularity in the testes tissue caused by cigarette smoke exposure can be improved with α-tocopherol and N-nitro L-arginine methyl ester application.

Posttreatment Effects of Olea Europaea L. Leaf Extract on Carbon Tetrachloride-Induced Liver Injury and Oxidative Stress in Rats.

The aim of this study is to examine the therapeutic effects of Olea europaea L. leaf extract on carbon tetrachloride (CCl4)-induced liver damage in rats. In the experiments, 3- to 4-month-old 28 male Sprague-Dawley rats were divided into four groups: control, O. europaea leaf extract, CCl4, and curative. The CCl4 and curative groups received CCl4 (0.2 mL/kg) intraperitoneally for 10 days to form hepatic injury. O. europaea (80 mg/kg) leaf extract was given orally to the curative group dissolved in distilled water the following 14 days. Hepatic and antioxidant enzyme levels, p53, caspase 3, lipid peroxidation marker malondialdehyde (MDA), and also DNA fragmentation levels were determined to establish oxidative stress in hepatic cell damage and its consequences. After formation of liver damage, oral administration of the O. europaea significantly reduced CCl4-induced elevations of serum alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase levels (P < .001), MDA levels of both blood (P < .001) and liver tissues (P < .001), DNA fragmentation (P < .001), p53 (P < .001), and caspase 3 (P < .001) levels of liver tissues. Also this administration in curative group significantly increased CCl4-induced reductions of superoxide dismutase (SOD) (P < .001) and catalase (CAT) (P < .001) activity of blood samples and decreased SOD (P < .001) and CAT (P < .05) activity observed in liver tissue curative groups compared with CCl4 curative group. In CCl4 group, liver tissue samples exhibited remarkable damage because of CCl4 and reduction of these damages were observed in the curative group. Our results showed that O. europaea leaf extract was effective in reducing hepatic damage caused by CCl4 by reducing lipid peroxidation, regulating antioxidant enzymes, and minimizing DNA damage.

Effects of S-allyl cysteine on lung and liver tissue in a rat model of lipopolysaccharide-induced sepsis.

Sepsis is characterized by a severe production of reactive oxygen species (ROS) and other radical species with consequent oxidative stress. S-allyl cysteine (SAC) is a water-soluble organosulfur component present in garlic which is a potent antioxidant and free radical scavenger. In the present study, the purpose was to explore the anti-inflammatory, antioxidant, and anti-apoptotic actions of SAC on lipopolysaccharide (LPS)-induced sepsis in rats. Thirty-two male Wistar rats were separated into 4 groups. These were control, SAC control, sepsis, and sepsis + SAC-induced groups. Sepsis was induced by administration of LPS (5 mg/kg) into 2 groups. SAC (50 mg/kg) was given orally to SAC control and SAC treatment groups per 12 h during 2 days after intraperitoneal LPS injection. Serum AST, ALT, ALP, and hsCRP levels and liver and lung MPO, NO, and DNA fragmentation levels were evaluated. In sepsis group, elevated levels of ALT, AST, ALP, and hsCRP were observed. The abnormal increases were decreased in sepsis + SAC group compared to sepsis group. In lung tissue, MPO and NO levels were increased in sepsis group compared to the control group. MPO activity and NO levels were decreased by SAC application in sepsis + SAC group compared with sepsis group. In liver tissue, DNA fragmentation was significantly higher in sepsis group than that in the control group. In contrast, a decreased level of DNA fragmentation was noted in sepsis + SAC group when compared with the sepsis group. In conclusion, SAC ameliorates LPS-induced indicators of liver damage and suppresses the discharge of NO and MPO in lung tissue via its antioxidant properties.

Apoptotic effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats.

We evaluated the effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl2]Cl) on apoptosis during chemically induced hepatocellular carcinoma. 48 male Spraque-Dawley rats were divided into six groups; group I (control), group II [Dimethyl sulfoxide (DMSO)], group III ([Au(dppz)Cl2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl2]Cl (7th week). The rats in groups IV through VI were administrated with DEN in a single dose of intraperitoneal 175 mg/kg. After 2 weeks of DEN administration, these groups of rats were given daily PB in a dose of 500 ppm. In group V, after two weeks of DEN administration, [Au(dppz)Cl2]Cl complex (2 mg/kg) was given once a week by intraperitoneal injection. In the group VI, the rats were given a dose of 2 mg/kg [Au(dppz)Cl2]Cl complex once a week, 7 weeks after DEN administration. At the end of the study, blood and tissue samples were collected from the rats to determine levels of serum AST, ALT, and LDH, and caspase 3, p53, Bax, Bcl-2 and DNA fragmentation in liver. AST, ALT, LDH, and Bcl-2 levels were higher in group IV, compared to group I, but caspase 3 and p53 levels were lower. In group V, caspase 3, p53, Bax, and DNA fragmentation levels were higher than those of group IV. Caspase 3 and p53 levels increased in group VI compared with group IV. In conclusion, [Au(dppz)Cl2]Cl complex induced apoptosis by elevating levels of caspase 3, p53, Bax, and DNA fragmentation.

Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation.

Inflammation has an important role in many diseases such as cystic fibrosis, allergies and cancer. The free radicals produced during inflammation, can induce gene mutations and posttranslational modifications of cancer related proteins. Nigella sativa L. (N. sativa) is herbaceous plant and commonly used as a natural food. It has many pharmacological effects including antibacterial, antifungal, antitumor, analgesic, antipyretic activity. The aim of this study was to investigate the anti-inflammatuar and anti-oxidant activity of N. sativa in acute inflammation. Thus we used the experimental lipopolysaccharides (LPS)-induced model. Intraperitoneal LPS 1 mg/kg was administered to groups. N. sativa (500 mg/kg) and essential oil (5 ml/kg) were given orally to treatment groups, after 24-h of intraperitoneal LPS-injection. To determine the lung inflammation, 18F-fluoro-deoxy-D-glucose (0.8 ml/kg) was administrated under the anesthesia before the 1 h of PET-scanning. After the FDG-PET, samples were collected. Lung and liver 18F-FDG-uptake was calculated. Serum AST, ALT, LDH and hcCRP levels were determined and liver, lung and erythrocyte SOD, MDA and CAT levels were measured. Liver and lung NO and DNA fragmentation levels were determined. MDA levels were decreased in treated inflammation groups whereas increased in untreated inflammation group. SOD and CAT activities in untreated inflammation group were significantly lower. According to the control group, increased AST and ALT levels were found in untreated inflammation group. 18F-FDG uptake of inflammation groups were increased when compare the control group. We found increased 18F-FDG uptake, DNA fragmentation and NO levels in LPS-induced inflammation groups. We conclude that, in LPS-induced inflammation, N. sativa have therapeutic and anti-oxidant effects.

Antioxidant and anti-apoptotic activity of vasoactive intestinal peptide (VIP) against 6-hydroxy dopamine toxicity in the rat corpus striatum.

6-Hydroxydopamine (6-OHDA) is an oxidative stress neurotoxin, which is oxidized in neurons, causes respiratory inhibition, and induces free radical formation and oxidative stress. Therefore, a 6-OHDA-induced Parkinson's disease (PD) experimental model can be used to test a candidate molecule for use as an antioxidant that could be a promising therapeutic for treating Parkinson's disease. Recent studies have shown that vasoactive intestinal peptide (VIP) might be a good candidate agent for the treatment of PD. In this study, the anti-apoptotic and antioxidant actions of VIP were investigated using the 6-OHDA-lesioned rat model for PD. Twenty-four young adult Sprague-Dawley rats were used. The rats were separated into the following groups: group I (n = 8), sham operated; group II (n = 8), 6-OHDA lesioned; group III (n = 8), 6-OHDA lesioned + i.p. VIP-injected (25 ng/kg) every 2 days for 15 days. The first i.p. injection of VIP was made 1 h after the intrastriatal 6-OHDA microinjection. Antioxidant enzymatic activity [super oxide dismutase (SOD) and catalase (CAT)], lipid peroxidation, nitric oxide and DNA fragmentation were measured from homogenates isolated from the corpus striatum. SOD, CAT, malondialdehyde, and DNA fragmentation were measured using a spectrophotometer, and nitric oxide (NO) levels were measured by capillary electrophoresis. 6-OHDA significantly induced oxidative stress, lipid peroxidation, and DNA fragmentation in the corpus striatum of rats. VIP significantly protected neuronal tissue from oxidative stress and apoptosis by reducing lipid peroxidation and DNA fragmentation. 6-OHDA toxicity did not cause significant changes in NO production in the corpus striatum. However, VIP treatment significantly reduced NO levels in brain tissue.

NO levels in diabetes mellitus: Effects of l-NAME and insulin on LCAT, Na(+)/K(+) ATPase activity and lipid profile.

OBJECTIVES: Diabetes mellitus (DM) is a chronic disease and one of the most important health problems. Several factors may be responsible for the complications of diabetes mellitus including alterations in the activities of sodium-potassium adenosine triphosphatase (Na(+)/K(+) ATPase) and lecithin:cholesterol acyltransferase (LCAT) and also levels of nitric oxide (NO). We have investigated the effects of alterations in serum NO levels on activities of erythrocyte membran Na/K ATPase and serum LCAT enzymes. MATERIALS AND METHODS: The experiments were performed on male rats divided into four groups: group 1, control (standart diet); group 2, diabetic control (single dose of 65mg/kg of streptozotocin (STZ), i.p); group 3, STZ+insulin (8IU/kg/day s.c.); group 4 (STZ+l-NAME 5mg/kg/day orally). RESULT: Streptozotocin-induced diabetic rats, showed a significant increase in blood glucose and serum cholesterol (C) and triglyceride (TG). Compared to the control group with diabetic group plasma LCAT concentrations and erythrocyte membrane Na(+)/K(+) ATPase were found to be decreased. Activities of Na(+)/K(+) ATPase and serum NO level were decreased with the administration of l-NAME. We observed that insulin was ameliorated in all parameters. CONCLUSIONS: Serum NO levels is related to erythrocyte membrane Na(+)/K(+) ATPase activity. But serum NO levels did not affect the plasma LCAT activity and serum lipid profiles.

The effects of CCl4 on Na+/K+-ATPase and trace elements in rats.

CCl4 is an industrial agent with known toxic effects on the environment. There are so many studies about hepatotoxic effects of CCl4. We herein studied the effects of CCl4 on Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities on erythrocyte membranes and trace element levels of serum erythrocyte and liver tissue of rats. Study was performed on control group (group C, n=8) and a study group (group S, n=8) in which CCl4 was given. Na+/K+-ATPase and Ca2+/Mg2+-ATPase were significantly reduced in CCl4-treated group (p<0.01, p<0.001). Trace element levels also showed statistically significant differences in CCl4-treated group. Membrane Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities were diminished due to CCl4-induced injury on erythrocyte membranes. CCl4 also changed the trace element levels of serum erythrocyte membrane and liver by altering the mineral substance concentrations.

The protective effect of NG-nitro-L-arginine methyl ester and insulin on nitric oxide inhibition and pathology in experimental diabetic rat liver.

OBJECTIVE: To determine on protective role of NG-nitro-L-arginine methyl ester L-NAME, and insulin on the liver in streptozotocin STZ induced diabetic rats. METHODS: This study was performed in the Department of Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. Forty male Wistar albino rats were divided into 5 groups. These were untreated, diabetic control, STZ+insulin, STZ+L-NAME and STZ+insulin+L-NAME induced groups. The STZ was intraperitonally injected into 3 groups, and includes insulin, L-NAME, and their joint administrations as protective agents. The blood glucose and nitric oxide (NO) levels were determined. The tissue samples were obtained at the end of the fourth week. The liver tissue distortions were evaluated using hematoxylin and eosin staining. RESULTS: The serum glucose level was significantly higher in diabetic control (p=0.000), than the untreated group. Nitric oxide level was significantly lower in STZ+L-NAME (p=0.000) than the untreated group. The focal pseudo lobular structures without vena centralis increased portal fibrillary necrosis, and bile duct stenosis with coagulation necrosis of the peripheral hepatocytes were more observed in diabetic group than the protective agent groups. In addition, insulin, and L-NAME lead to hepatocyte regeneration; and minimal mononuclear cell infiltration was noted. CONCLUSION: NG-nitro-L-arginine methyl ester inhibits NO level in STZ+L-NAME induced group. NG-nitro-L-arginine methyl ester either alone, or with insulin combination significantly attenuates the liver morphological disarrangements in STZ induced diabetic rats.

The effects of captopril and losartan on erythrocyte membrane Na+/K(+)-ATPase activity in experimental diabetes mellitus.

Diabetes mellitus induces a decrease in sodium potassium-adenosine triphosphatase (Na+/K(+)-ATPase) activity in several tissues in the rat and red blood cells (RBC) and nervous tissue in human patients. This decrease in Na+/K(+)-ATPase activity is thought to play a role in the development of long-term complications of the disease. Angiotensin enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARBs) reduce proteinuria and retard the progression of renal failure in patients with IDDM and diabetic rats. We investigated the effects of captopril and losartan, which are used in the treatment of diabetic nephropathy, on Na+/K(+)-ATPase activity. Captopril had an inhibitory effect on red cell plasma membrane Na+/K+ ATPase activity, but losartan did not. Our study draws attention to the inhibitory effect of captopril on Na+/K+ ATPase activity. Micro and macro vascular complications are preceeding mortality and morbidity causes in diabetes mellitus. There is a strong relationship between the decrease in Na+/K+ ATPase activity and hypertension. The non-sulphydryl containing ACEi and ARBs must be the choice of treatment in hypertensive diabetic patients and diabetic nephropathy.

Nickel and cadmium concentrations in plasma and Na+/K+ ATPase activities in erythrocyte membranes of the people exposed to cement dust emissions.

The aim of this study was to determine the concentrations of nickel and cadmium in blood plasma of the people exposed to cement dust emissions and to investigate the effects of exposure period on the activities of Na+/K+ ATPase enzymes in their erythrocyte membranes. The study was carried out on people living in Eskisehir Cukurhisar rural area, located near a cement factory. Blood samples of the individuals residing in this area were taken from 80 subjects (30 for control) following a physical examination. The analysis of plasma samples showed that nickel concentrations in subject group were found to be significantly higher than those of the control group (p < 0.001). Cadmium concentrations were found to be within the reference values for both group and no difference was found between the subjects and controls (p > 0.05). Furthermore, no correlation was observed between the levels of Na+/K+ ATPase activity in erythrocyte membranes of the subject group and the ages of people living in the region (p > 0.05, r = 0.133). It was also observed that nickel concentrations increased by age (p < 0.001, r = 0.646) while no effect was observed in means of cadmium. Na+/K+ ATPase activities in the erythrocyte membranes were not affected. In conclusion although there was no difference between the Na+/K+ ATPase activity in means of age, there was an environmental pollution and may be it was due to the industrial plant.

Effect of quercetine and glutathione on the level of superoxide dismutase, catalase, malonyldialdehyde, blood pressure and neonatal outcome in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl ester.

OBJECTIVE: To anticipate the impact of antioxidant use on lipid peroxidation products, free oxygen radical scavengers, blood pressure (BP), proteinuria and neonatal outcome (as seen in percentage survival, litter birth weight) in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of nitric oxide synthase (NOS). MATERIAL AND METHODS: Female adult non-pregnant Sprague-Dawley rats (n=40) with timed pregnancies were allocated into four groups according to medication they received on day 17 to term. Rats were randomised into a sham-treated group (group I, n=10) and groups treated with L-NAME, 50 mg/day i.p., only (group II, n=10), L-NAME + quercetine, 10mg/kg i.p. (group III, n=10) and L-NAME + glutathione, 60 mg/kg i.p. (group IV, n=10). Blood levels of superoxide dismutase (SOD), catalase (CAT) and malonyldialdehyde (MDA) were assessed on day 22 of gestation. Intracardiac blood sampling and hysterotomy were performed on day 22 of gestation. Mean systolic BP (measured with a tail-cuff device), level of proteinuria, total urine output, pups birth weight and percentages of live and of dead pups were recorded. RESULTS: Mean systolic BP and SOD, CAT and MDA levels were higher in rats infused with L-NAME than in the sham-treated group. In group IV, SOD levels were lower than in group II (P <0.001). A linear positive correlation between BPs on day 20 and SOD levels (rp=0.39) was recorded, as were negative correlations between level of proteinuria and SOD levels (rp=-0.39) and between CAT and MDA levels (rp=-0.39). Birth weights were higher in the sham-treated group than in the other groups (P <0.001). Pups of hypertensive gravid rats treated with antioxidants had better survival rates than those of rats in group II and the sham-treated group (Chi-square=15.9, d.f.: 3, P <0.01).However, no correlation was detected between higher pup mortality rate and birth weight of pups. CONCLUSION: In this rat model of pre-eclampsia, adverse outcomes, such as proteinuria and high neonatal death rate, are reversed by exogenous antioxidant use, even though no significant improvement is detected in terms of BP and birth weight of pups.

Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic reperfusion injury.

The aim of the present study was to determine the potential therapeutic value of 21-aminosteroid U-74389G, on blood-brain barrier (BBB) breakdown and edema in association with the changes in synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPase activities in rat brain subjected to post-ischemic reperfusion injury. Brain ischemia was achieved by means of four-vessel occlusion model for 25 min and animals were sacrificed after 12 h reperfusion. An increase of cerebral tissue water content, blood-brain disruption and the changes of synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPases activities were evaluated. U-74389G was given intraperitoneally at two times as 5 mg/kg at 10 min prior to ischemia and at the beginning of reperfusion. Edema was determined by means of wet-dried weight method, and BBB of extravasation of Evan's blue dye. Extravasation of Evan's blue dye into brain following ischemia and reperfusion was 2.4-fold of control value and brought close to control levels by the effect of U-74389G (p<0.001). Post-ischemic reperfusion injury caused an increase of 3.7% in tissue water content of whole brain and administration of U-74389G lowered the cerebral edema (p<0.001). The loses in the Na(+)/K(+)-ATPase and Mg(2+)/Ca(2+)-ATPase activities occurred as 42.1% (p<0.01) and 65.7% (p<0.001) of control value, respectively. While Mg(2+)/Ca(2+)-ATPase activity was enhanced compared to vehicle-treated group of animals (p<0.01), Na(+)/K(+)-ATPase activity was fully recovered when compared to control by U-74389G (p>0.05). U-74389G also significantly attenuated neuronal necrosis (p<0.001) which was determined in the hippocampal CA1 subfield. Blood-brain barrier protection, attenuation of brain edema and neuronal necrosis concomitant with the stabilizing of membrane-bound enzymes brought about by the effect of U-74389G suggest that 21-aminosteroids are worthy of consideration in the acute treatment of cerebral ischemia.

Lazaroid attenuates edema by stabilizing ATPase in the traumatized rat brain.

OBJECTIVE: The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma. METHODS: Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals. RESULTS: Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1% (p<0.001) at 24h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg(2+)/Ca(2+)-ATPase activities were found as 39.5% (p<0.001) and 29.4% (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209% (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05). CONCLUSION: U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.