Effects of agomelatine on rat liver regeneration following partial hepatectomy.

Primary or metastatic hepatic malignancies are common. Partial hepatectomy (PH) is the primary treatment for both benign and malignant hepatic neoplasms; it also is used for living donor liver transplantation. The regenerative potential of the liver after PH is 70-80% in humans. We investigated the protective and therapeutic effects of agomelatine (AGM) on rat liver regeneration following PH. We used 32 rats distributed equally into four groups: group 1, sham control; group 2, PH group; group 3, administered 20 mg/kg AGM orally once/day for 7 days following PH; group 4, administered 20 mg/kg AGM orally once/day 3 days before and 7 days following PH for 10 days. Liver samples were analyzed for antioxidants and free radicals. Tissue samples were processed and stained with hematoxylin and eosin to assess histopathological status and stained immunohistochemically for Ki-67. We found that PH reduced antioxidant enzymes and increased tissue reactive oxygen species, whereas AGM treatment had the opposite effect on these parameters. Our biochemical and histopathological findings were consistent. PH caused sinusoid congestion and dilation. Intensity of Ki-67 immunostaining of hepatocytes was increased in group 2, whereas these were reduced in group 4. Intensity of Ki-67 immunostaining of hepatocytes was increased in group 2, whereas it was reduced in the group 4 compared to group 1. We found that AGM was hepatoprotective following PH due to its antioxidant and free radical scavenger properties.

Effect of a honey and arginine-glutamine-hydroxymethylbutyrate mixture on the healing of colon anastomosis in rats immunosuppressed with tacrolimus.

We compared the effect of honey and a mixture of arginine-glutamine-hydroxymethylbutyrate (AGHMB) on healing of a descending colon anastomosis in rats that were immunosuppressed with tacrolimus (Tac). Sprague-Dawley rats were divided into four groups: untreated control, Tac, Tac + honey and Tac + AGHMB. Colon resection and anastomosis were performed on day 14 and re-laparotomy was performed on the day 21 of the study. Anastomotic bursting pressure, macroscopic adhesion score, weekly body weight changes, histopathological features and immunohistochemical staining of TGF-ß1 were determined for all groups. We found no significant difference in anastomotic bursting pressure among the experimental groups. We found significant weekly increases in body weight for the Tac + honey group. We found no significant difference in the weekly body weight measurements for the Tac + AGHMB group. We found significant increases in TGF-ß1 expression in the Tac + honey group compared to the control and Tac groups. No significant differences in inflammatory cell infiltration, fibroblast proliferation or collagen deposition were found between the Tac + honey and Tac + AGHMB groups; however, a significant difference in neovascularization between these groups was found. Neovascularization in the Tac + honey group was significantly greater than for the Tac + AGHMB group. We found that both honey and the AGHMB mixture were beneficial for anastomotic wound healing in rats that were immunosuppressed using Tac.

Neuroprotection against CCl4 induced brain damage with crocin in Wistar rats.

Owing to its lipophilic property, carbon tetrachloride (CCl4) is rapidly absorbed by both the liver and brain. We investigated the protective effects of crocin against brain damage caused by CCl4. Fifty rats were divided into five groups of ten: control, corn oil, crocin, CCl4 and CCl4 + crocin. CCl4 administration decreased glutathione (GSH) and total antioxidant status (TAS) levels, and catalase (CAT) activity, while significant increases were observed in malondialdehyde (MDA) and total oxidant status (TOS) levels and superoxide dismutase (SOD) activity. The cerebral cortex nuclear lamina developed a spongy appearance, neuronal degeneration was observed in the hippocampus, and heterochromatic and pyknotic neurons with increased cytoplasmic eosinophilia were observed in the hippocampus after CCl4 treatment. Because crocin exhibits strong antioxidant properties, crocin treatment increased GSH and TAS levels and CAT activities, and decreased MDA and TOS levels and SOD activity; significant improvements also were observed in histologic architecture. We found that crocin administration nearly eliminated CCl4 induced brain damage by preventing oxidative stress.

Effects of molsidomine on retinal ischemia/reperfusion injury in rabbits.

We investigated the effect of molsidomine (MOL) on ischemia/reperfusion (I/R) injury. Rabbits were assigned to four groups: group 1, sham; group 2, I/R; group 3, MOL treatment for 4 days after I/R; group 4, MOL treatment for 1 day before I/R and 3 days after I/R. Retinal I/R was produced by elevating the intraocular pressure to 150 mm Hg for 60 min. Seven days after I/R, the eyes were enucleated. Retinal changes were examined using histochemistry. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) also were measured. We found a significant increase in the thickness of the outer nuclear layer of group 3 compared to the other groups. In groups 3 and 4, caspase-3 stained cells in the ganglion cell layer were decreased compared to group 2. We found a significant increase in caspase-3 stained cells in the inner nuclear layer (INL) of group 2 compared to the other groups. We found a significant increase in caspase-3 stained cells in group 3 compared to group 4 in the INL. The MDA level in group 2 was significantly higher than group 1 and MOL significantly decreased MDA levels in groups 3 and 4. We found that MOL protected the retina from I/R injury by enhancing antioxidative effects and inhibiting apoptosis of retinal cells.

The role of the eNOS G894T and T-786C gene polymorphism in the development of ascites in cirrhosis.

OBJECTIVE: Increased nitric oxide (NO) production in cirrhotic patients causes splanchnic vasodilation, leading to the development of the hyperdynamic circulatory syndrome. One factor that influences plasma NO concentration is eNOS gene polymorphism; consequently, the aim of this study was to investigate whether the eNOS gene G894T and T-786C polymorphisms play any role in the development of ascites in such patients. PATIENTS AND METHODS: Three groups were created: 70 cirrhotic patients with ascites, 69 cirrhotic participants without ascites (stable cirrhosis), and 60 healthy controls. Polymorphisms were determined using polymerase chain reaction (PCR) and melting curve analysis. The plasma nitrite (NO marker) level was measured by deploying the spectrophotometric Griess reaction. RESULTS: Plasma nitrite levels in the cirrhosis with ascites and stable cirrhosis groups were significantly higher than in the controls (p < 0.0001). The frequency of GG, GT, and TT genotypes for the eNOS G894T polymorphism in the cirrhosis with ascites group was 55.7%, 38.6%, and 5.7% respectively, while in the stable cirrhosis group these figures were 60.9%, 36.2%, and 2.9%. In the controls, the distribution was 63.3%, 33.3%, and 3.3%, respectively. The frequency of TT, TC, and CC genotypes for the eNOS-786C polymorphism in the first group was 52.9%, 34.2%, and 12.9% respectively; in the second group, this was 46.4%, 42%, and 11.6%, and in the controls, 48.3%, 46.7%, and 5%. There were no significant differences in genotype and allele distributions of the eNOS-786C and eNOS G894T polymorphisms among the groups. CONCLUSIONS: Plasma nitrite concentration is enhanced in cirrhotic patients, and there is no relationship between the G894T and eNOS-786C polymorphisms and the development of ascites.

The effects of caffeic acid phenethyl ester on streptozotocin-induced diabetic liver injury.

The aim of the present study was to clarify the role of oxidative stress in streptozotocin induced liver injury and the possible protective effect of caffeic acid phenethyl ester (CAPE) using histological and biochemical parameters. 32 male Wistar rats were divided into 4 groups as follows: Group 1: Control animals, Group 2: Control animals given CAPE Group 3: STZ-induced diabetic animals (DM group), Group 4: STZ-induced diabetic rats given CAPE (DM+CAPE group). All the injections started on the same day of single-dose STZ injection and continued for 20 days. At the end of this period, livers were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased compared with the control group. Significant increases in tissue malondialdehyde (MDA) level and decreases in superoxide dismutase (SOD) and total glutathione (GSH) activities were detected in DM group. Administration of CAPE significantly reduced these values. STZ-induced histopathological alterations including inflammatory cell infiltration around portal triad, congestion, loss of glycogen in the hepatocytes. Additionally, degenerative cellular alterations, such as numerous vacuolizations including myelinic figure formation, pyknotic nuclei with peripheral localization of heterochromatin condensation and mitochondrial elongation were observed in cytoplasm of hepatocytes. CAPE significantly reduced these histopathological changes. Our results indicate that CAPE should be considered in the prevention of oxidative stress in diabetic liver.

Investigation of the effects of acrylamide applied during pregnancy on fetal brain development in rats and protective role of the vitamin E.

A liberal amount of acrylamide (AA) is produced as a result of frying or baking foods in high temperatures, and individuals take certain amounts of AA everyday by consuming these food items. Pregnant women are also exposed to AA originating from food during pregnancy and their fetus are probably affected. The rats were divided into five different groups: control (C), corn oil (CO), vitamin E (Vit E), AA, and Vit E + AA, with eight pregnant rats in each group. On the 20th day of pregnancy, fetuses were removed and brain tissues of fetuses were examined for biochemical and histological changes. AA caused degeneration in neuron structures in fetal brain tissue and caused hemorrhagic damages; dramatically decreased brain-derived neurotrophic factor levels; increased malondialdehyde, total oxidant capacity levels; and decreased reduced glutathione and total antioxidant capacity levels (p < 0.05). On the other hand, it was determined that the Vit E, a neuroprotectant and a powerful antioxidant, suppressed the effects of AA on fetal development and fetal brain tissue damage for the above-mentioned parameters (p < 0.05). It is recommended to consume food containing Vit E as a protection to minimize the toxic effects of food-oriented AA on fetus development due to the widespread nature of fast-food culture in today's life and the impossibility of protection from AA toxicity.

Quercetin protection against ciprofloxacin induced liver damage in rats.

Ciprofloxacin is a common, broad spectrum antibacterial agent; however, evidence is accumulating that ciprofloxacin may cause liver damage. Quercetin is a free radical scavenger and antioxidant. We investigated histological changes in hepatic tissue of rats caused by ciprofloxacin and the effects of quercetin on these changes using histochemical and biochemical methods. We divided 28 adult female Wistar albino rats into four equal groups: control, quercetin treated, ciprofloxacin treated, and ciprofloxacin + quercetin treated. At the end of the experiment, liver samples were processed for light microscopic examination and biochemical measurements. Sections were prepared and stained with hematoxylin and eosin, and a histopathologic damage score was calculated. The sections from the control group appeared normal. Hemorrhage, inflammatory cell infiltration and intracellular vacuolization were observed in the ciprofloxacin group. The histopathological findings were reduced in the group treated with quercetin. Significant differences were found between the control and ciprofloxacin groups, and between the ciprofloxacin and ciprofloxacin + quercetin groups. Quercetin administration reduced liver injury caused by ciprofloxacin in rats. We suggest that quercetin may be useful for preventing ciprofloxacin induced liver damage.

Beneficial effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin in rats: A histological and biochemical study.

Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg(-1) day(-1) gavage for 21 days), ciprofloxacin (20 mg kg(-1) twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman's space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues.

The aim of this study was to investigate the protective effects of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues in rats.The rats were divided into four groups. Acrylamide administration increased MDA levels in all tissues significantly (p < 0.05). But acrylamide+NAC administration decreased MDA levels significantly as compared to the acrylamide group, and lowered it to a level close to the control group values (p < 0.05). GSH levels in liver and small intestine tissues reduced significantly in the acrylamide group (p < 0.05). But acrylamide+NAC administration increased GSH levels significantly in all tissues. Whereas GST activity decreased significantly in the acrylamide group in liver and small intestine tissues as compared to the other groups (p < 0.05), the GST activity increased significantly in the acrylamide+NAC group in all tissues as compared to the acrylamide group (p < 0.05). Liver histopathology showed that the liver epithelial cells were damaged significantly in the acrylamide group. Small intestine histopathology showed that the intestinal villous epithelial cells were damaged significantly in the acrylamide group.Our results indicate that a high level of acrylamide causes oxidative damage in liver and small and large intestine tissues, while N-acetylcysteine administration in a pharmacological dose shows to have an antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66).

Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats.

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia-reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (p < 0.01) and XO (p < 0.05) activities and elevated GSH (p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin.

Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p < 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p < 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.

The effects of montelukast against amikacin-induced acute renal damage.

BACKGROUND AND OBJECTIVES: The therapeutic and protective effects of montelukast against amikacin-induced acute renal damage were investigated. MATERIAL AND METHODS: 35 Wistar albino female rats were divided into 5 groups as follows: Group I: Control; Group II: Control+montelukast; Group III: Amikacin; Group IV: Amikacin+montelukast; Group V: Montelukast+amikacin. At the end of the experiment, the kidney tissues and the blood of rats were collected. Malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione (GSH) levels were determined from kidney tissues. Blood urea nitrogen (BUN), creatinine (Cr), TNF-alpha, and IL-1beta levels were assessed in the serum. In addition the kidney tissues were examined histologically. RESULTS AND DISCUSSION: The MDA, MPO, BUN, and Cr levels of group III significantly increased when compared to groups I and II. These parameters of group IV decreased when compared to group III. In addition, GSH levels significantly increased when compared to the first three groups. MDA, BUN and Cr levels of group V did not reach significant level in comparison with the control group. The most significant histological damage was observed in the group III followed by the groups IV and V. Immunohistochemically, group III showed a significantly increased apoptotic staining. In group IV, it was observed that montelukast treatment reduced the expression of apoptotic cells. CONCLUSIONS: Montelukast treatment after amikacin injection could reduce the amikacin-induced kidney damage.

Effects of electromagnetic radiation produced by 3G mobile phones on rat brains: magnetic resonance spectroscopy, biochemical, and histopathological evaluation.

OBJECTIVE: The effects of electromagnetic radiation (EMR) produced by a third-generation (3G) mobile phone (MP) on rat brain tissues were investigated in terms of magnetic resonance spectroscopy (MRS), biochemistry, and histopathological evaluations. METHODS: The rats were randomly assigned to two groups: Group 1 is composed of 3G-EMR-exposed rats (n = 9) and Group 2 is the control group (n = 9). The first group was subjected to EMR for 20 days. The control group was not exposed to EMR. Choline (Cho), creatinin (Cr), and N-acetylaspartate (NAA) levels were evaluated by MRS. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were measured by spectrophotometric method. Histopathological analyses were carried out to evaluate apoptosis in the brain tissues of both groups. RESULTS: In MRS, NAA/Cr, Cho/Cr, and NAA/Cho ratios were not significantly different between Groups 1 and 2. Neither the oxidative stress parameters, CAT and GSH-Px, nor the number of apoptotic cells were significantly different between Groups 1 and 2. CONCLUSIONS: Usage of short-term 3G MP does not seem to have a harmful effect on rat brain tissue.

Melatonin ameliorates cerebral vasospasm after experimental subarachnoidal haemorrhage correcting imbalance of nitric oxide levels in rats.

In the present study, we investigated the in vivo effects of melatonin on SAH-induced cerebral vasospasm and oxidative stress, resulting from SAH in an experimental rat model. Twenty-eight rats (225-250 g) were divided into four groups equally: group 1; control, group 2; SAH, group 3; SAH plus placebo, and group 4; SAH plus melatonin. We used double haemorrhage method for SAH groups. Beginning 6 h after SAH, 20 mg/kg melatonin or equal volume of 0.9% saline was administered intraperitoneally twice daily for 5 days to groups 3 and 4, respectively. Melatonin or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificed at the end of this period. Brain sections at the level of the pons were examined by light microscopy. The lumen diameter and the vessel wall thickness of basilar artery were measured using a micrometer. The serum levels of cerebral vasodilator nitric oxide (NO), the brain levels of an intrinsic antioxidant superoxide dismutase (SOD) and a NO regulator arginase activities were measured. The brain levels of inducible nitric oxide (iNOS) and nitrotyrosine, a nitrosative stress parameter immunohistochemiacally determined. In conclusion, melatonin administration ameliorated cerebral vasospasm by increasing serum NO level and decreasing the brain the levels of arginase and oxidative stress. It is therefore possible that increased brain arginase activity after SAH may also have a significant role in the pathogenesis of vasospasm by limiting the availability of arginine for NO production.

Effect of resveratrol in experimental osteoarthritis in rabbits.

OBJECTIVE: Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found in high concentration in the skins of grapes and red wines which has been shown to have antiinflammatory, anticancerogen and antioxidant properties. Resveratrol is a potent and specific inhibitor of nuclear factor kappa B (NF-kappaB). Resveratrol also inhibits COX-2 gene expression and enzyme activity. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental osteoarthritis (OA) model in rabbits. METHODS: As OA model, rabbits underwent unilateral anterior cruciate ligament transection (ACLT). Five weeks after test group was injected with 10 microMol/kg resveratrol in dimethylsulphoxide (DMSO) in the knees once daily for two weeks and as the control group at the same time DMSO was injected into the knees. All rabbits were killed one week after the last injection. Cartilage tissue and synovium were evaluated with a histological scoring system. RESULTS: Histological evaluation of cartilage tissue by H&E staining revealed a significantly reduced average cartilage tissue destruction score of 1.7 in the resveratrol group versus 2.8 in the control group (p = 0.016). Loss of matrix proteoglycan content in cartilage was also much lower, as determined by safranin O staining. Scores of synovial inflammation didn't show difference between groups (1.3 vs 2.2; p = 0.057). CONCLUSION: A characteristic parameter in arthritis is the progressive loss of articular cartilage. This study suggests that intraarticular injections of resveratrol starting at the onset of disease may protect cartilage against the development of experimentally induced OA.

Protective effects of melatonin on myocardial ischemia/reperfusion induced infarct size and oxidative changes.

Free radicals, calcium overloading and loss of membrane phospholipids play an important role in the development of ischemia/reperfusion (I/R) injury. Melatonin is a well-known antioxidant and free radical scavenger. Melatonin may also reduce the intracellular calcium overloading and inhibit lipid peroxidation. This study was designed to investigate the effects of melatonin on the I/R-induced cardiac infarct size in an in vivo rat model. We also investigated glutathione (GSH) levels, an antioxidant the levels of which are influenced by oxidative stress, and malondialdehyde (MDA) levels, which is an index of lipid peroxidation. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Melatonin (10 mg/kg) or vehicle was given 10 min before ischemia via the jugular vein. Infarct size, expressed as the percentage of the risk zone, was found significantly greater in I/R group than in the melatonin-treated I/R group. MDA levels were significantly higher, but GSH levels were lower in the I/R group than in the control group. Melatonin significantly reduced the MDA values and increased the GSH levels. These results suggest that oxidative stress contributes to myocardial I/R injury and melatonin administration exerts a mitigating effect on infarct size. Furthermore, the results indicated that melatonin improves the antioxidant capacity of the heart and attenuates the degree of lipid peroxidation after I/R.

Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats.

Aminoglycoside antibiotics have long been used in antibacterial therapy. Despite their beneficial effects, aminoglycosides have considerable nephrotoxic and ototoxic side effects. It has been reported that reactive oxygen radical species (ROS) play role in the pathophysiology of aminoglycosides-induced nephrotoxicity. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against nephrotoxicity. We investigated the effects of AG on amikacin (AK)-induced changes of renal malondialdehyde (MDA), glutathione (GSH), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) which are used to monitor the development of renal tubular damage. Morphological changes in the kidney were also examined using light microscopy. A total of 21 rats were equally divided into three groups which were: (1) injected with saline, (2) injected with AK, and (3) injected with AK + AG, respectively. AK administration to control rats increased renal MDA and decreased GSH levels. AG administration before AK injection caused significant decreases in MDA and increases in GSH levels in kidneys compared to rats treated with AK alone. The serum BUN level increased slightly, Cr and serum Alb did not change as a result of any treatment. AG tended to decrease the level of serum BUN and did not cause any change in Alb or Cr levels. Morphological changes, including glomerular, tubular epithelial alterations and interstitial edema, were clearly observed in AK-treated rats. In addition, AG reversed the morphological damage to the kidney induced by AK. The results show that AG has a protective effect on nephrotoxicity induced by AK and may therefore improve the therapeutic index of AK.

Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behçet's syndrome.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a cytokine participating in inflammation with potent endothelial cell effects. It is produced by macrophages, neutrophils and vascular endothelial cells and can alter vessel permeability. Behçet's syndrome is a systemic inflammatory disorder with unknown etiology. Vascular endothelial dysfunction is one of the prominent features of the disease. We previously demonstrated the possible involvement of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, soluble interleukin-2 receptor (sIL-2R), interleukin (IL)-6 and IL-8], nitric oxide (NO) and adrenomedullin in the etiopathogenesis of Behçet's syndrome. Since VEGF expression is induced by these cytokines and VEGF itself is a potent stimulator of NO production with endothelial cell effects, this study aimed to investigate whether VEGF was affected during the course of Behçet's syndrome. We also assessed the possible involvement of VEGF in ocular Behçet's syndrome or in disease activity. METHODS: This multicenter case-control study included a total of 39 patients with active (n = 22) or inactive (n = 17) Behçet's syndrome (mean age, 38.1 +/- 10.4 years; 21 men and 18 women) satisfying International Study Group criteria, and 15 healthy hospital-based control volunteers (mean age, 39.2 +/- 9.3 years; eight men and seven women) matched for age and gender from a similar ethnic background. Patients were examined by a dermatologist and an ophthalmologist with an interest in Behçet's syndrome. Plasma VEGF concentrations were measured using a newly established enzyme-linked immunosorbent assay. Clinical findings and acute-phase reactant parameters such as erythrocyte sedimentation rate, alpha1-antitrypsin, alpha2-macroglobulin, and neutrophil count were used to classify the disease in Behçet's patients as active or inactive. The Wilcoxon test or the Mann-Whitney U-test was used for statistical analysis as indicated and the results were expressed as mean +/- SD, with range. RESULTS: The mean plasma VEGF level in patients with Behçet's syndrome (291.9 +/- 97.1 pg/mL; range 121-532 pg/mL) was higher than that in control subjects (103.0 +/- 43.6 pg/mL; range 25-187 pg/mL) and the difference was significant (P < 0.001). Patients with active disease had significantly (P < 0.001) higher VEGF levels than patients with inactive disease (347.6 +/- 87.1 vs. 219.9 +/- 51.6 pg/mL). In addition, ocular Behçet's patients (n = 23) had higher VEGF levels (315.7 +/- 92.1 pg/mL) than nonocular patients (n = 16, 257.8 +/- 96.6 pg/mL) and the difference was of borderline significance (P = 0.041). The levels of all acute-phase reactant parameters were significantly higher in the active stage than in the inactive stage (for each, P < 0.01) or in control subjects (for each, P < 0.001). CONCLUSIONS: VEGF may participate in the course of Behçet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.

The attenuation of vasospasm by using a sod mimetic after experimental subarachnoidal haemorrhage in rats.

BACKGROUND: Delayed cerebral vasoconstriction and brain ischemia, are critical problems in the management of a patient affected by rupture of an intracranial aneurysm. Overexpression of Cu-Zn superoxide dismutase (Cu-Zn SOD) can reduce the extent of cerebral vasospasm. We, therefore investigated if vasospasm, can be prevented by a novel, stable, and cell permeable SOD mimetic, MnTBAP [Mn(III) tetrakis (4-benzoic acid) porphyrin] which permeates the biological membranes and scavenges superoxide anions and peroxynitrite. METHODS: 28 rats (225-250 g) were divided equally into four groups: group 1: control; group 2: SAH only; group 3: SAH plus placebo; and group 4: SAH plus MnTBAP. We used a double haemorrhage method to produce SAH. Starting six hours after SAH, 5 mg/kg MnTBAP (Calbiochem, Darmstadt-Germany; Cat. No 475870)) or an equal volume of 0.9% saline (37 degrees C) was administered by intraperitoneal injection twice daily for 5 days to groups 4 and 3 respectively. MnTBAP or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificed on the fifth day. Brain sections at the level of the pons were examined by light microscopy. Planimetric measurements were made for the cross-sectional areas of the lumen and the vessel wall (intima plus media) of the basilar artery by a micrometer. FINDING: Administration of MnTBAP significantly attenuated the vasoconstriction of the basilar artery in group 4 compared with the groups 2 and 3 (p<0.001). INTERPRETATION: These results suggest that this SOD mimetic (MnTBAP) attenuates delayed cerebral vasoconstriction following experimental SAH and that superoxide anions have a role in the pathogenesis of vasospasm after SAH.