High cholesterol diet leads to oxidant load and peroxidation in the rabbit kidney tissue.

OBJECTIVES: The aim of this study was to investigate possible effects of high cholesterol diet on oxidant/antioxidant status in rabbit kidney tissues. BACKGROUND: Although a number of experimental animal models have suggested that hyperlipidemia is associated with progressive kidney failure data remain sparse on the role of dietary cholesterol intake on kidney disease. METHODS: Twelve male New Zealand albino rabbits were randomly divided into two groups (control and cholesterol). Both groups were fed on a standard laboratory diet. Animals in the cholesterol group additionally received cholesterol (1 g/kg/day), orally. The study period was 12 weeks. Activities of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide synthase (NOS), xanthine oxidase (XO), paraoxonase (PON), adenosine deaminase (ADA) enzymes and levels of malondialdehyde (MDA) and nitric oxide (NO) were measured in kidney tissue samples. Histological examination of the kidney tissue samples was also done. RESULTS: SOD, GSH-Px and XO enzyme activities were found to be decreased and NOS and PON activities increased significantly in cholesterol group compared to controls. As an indication of oxidation, MDA levels were found to be increased in cholesterol group. Histological examination revealed some derangements in the kidney tissue. CONCLUSION: High cholesterol diet creates oxidant load and causes peroxidation, which in turn, leads derangements in the rabbit kidney tissue (Tab. 2, Fig. 2, Ref. 69).

Effects of aqueous soybean, mistletoe and red clover extracts on activities of adenosine deaminase and xanthine oxidase enzyme.

Soybean (Glycine max), mistletoe (Viscum album) and red clover (Trifolium pratence) have been argued to have anti-cancer effects. In the present study it was aimed to investigate possible effects of these plant extracts on the activities of DNA turn-over enzymes, namely adenosine deaminase (ADA) and xanthine oxidase (XO) in cancerous and non-cancerous gastric and colon tissues. For this aim, 6 cancerous and 6 non-cancerous adjacent human gastric tissues, and 7 cancerous and 7 non-cancerous adjacent colon tissues were obtained by surgical operations. Our results suggest that aqueous soybean, mistletoe and red clover extracts may exhibit anti-tumoral activity by depleting hypoxanthine concentration in the cancer cells through XO activation, which may lead to lowered salvage pathway activity necessary for the cancer cells to proliferate in the cancerous colon tissue. Some foods like soybean, mistletoe and red clover may provide nutritional support to medical cancer therapy through inhibiting and/or activating key enzymes in cancer metabolism (Tab. 4, Ref. 33).

The effects of dexamethasone on oxidant/antioxidant status in kidneys of rats administered mercuric chloride.

The study was aimed to evaluate the possible effects of dexamethasone on oxidant/antioxidant status in kidney tissues of rats administered mercuric chloride (HgCl2). Thirty male Wistar-albino rats were enrolled in this study. Rats were divided into 4 groups: G1 (n=7) underwent no therapy (control group), G2 (n=8) received HgCl2 + physiological saline, G3 (n=7) dexamethasone (DM) + physiological saline and G4 (n=8) received HgCl2 + DM. HgCl2 was injected subcutaneously into rats in the G2 and G4 on the first day of the study. Dexamethasone was injected intraperitoneally into rats in the G3 and G4 for 3 days. Malondialdehyde (MDA) levels, catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and superoxide dismutase (SOD) activities were evaluated in the kidney tissues. Serum creatinine levels were also measured. Xanthine oxidase activity was increased in the G2 compared to the control group. Catalase activity in the control group was significantly higher compared to the other groups. In the histopathological examination of kidneys, there was a tubular degeneration in G2 and G4. It was concluded that HgCl2 administration may cause oxidative stress through increasing XO and decreasing CAT activities. Dexamethasone injection may partially protect the rat kidneys against oxidative reactions by preventing the increase in XO activity (Tab. 1, Ref. 33).

Nitric oxide metabolism in cancerous and non-cancerous oral gingivomucosal tissues: possible implications of nitric oxide in cancer process.

PURPOSE: Nitric oxide (NO) is a molecule that plays various roles in the body tissues. NO plays important roles in vasodilatation, platelet aggregation, cytokine stimulation, neurotransmission, immune function, etc. NO also exerts dual functions as an oxidant and antioxidant substance depending on its concentrations and environmental conditions. In this study, we aimed to examine possible correlation between NO levels and NO synthase (NOS) activity in the patients with oral cancer. MATERIALS AND METHODS: The study included 19 tissues from human subjects (11 malign and eight benign lesions). RESULTS: NO level and NOS activity were found decreased in the malign lesions compared with those of the benign ones. CONCLUSIONS: In conclusion, two suggestions can be made; first, decreased NO synthesis may be an attempt to suppress angiogenesis, which is known to provide more essential nutrients to malign lesions and/or second, malign lesions may suppress NO production to be capable of creating more rapid proliferation as it has been known that NO is also a powerful free radical inducing apoptosis.

Effect of propolis on oxidative stress and histomorphology of liver tissue in experimental obstructive jaundice.

BACKGROUND: Propolis is a natural product collected by honey bees from various plant sources. We aimed to determine the possible effects of propolis on oxidative stress and hepatocyte apoptosis in experimental obstructive jaundice. METHODS: Thirty rats were divided into three groups: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BDL followed by oral supplementation of propolis in a daily dose of 100 mg/kg. Liver samples were examined under the light microscope and transmission electron microscope. Hepatocyte apoptosis was quantitated using the transferase-mediated uridine nick end labeling (TUNEL) assay. Plasma and liver malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were measured. RESULTS: The plasma and liver levels of MDA were significantly lower in the propolis group than in the BDL group (p < 0.05 and 0.014, respectively). Although liver GSH-Px activities were significantly higher in the propolis group than in the BDL group (p < 0.001), there was no significant difference between the plasma GSH-Px activities of these groups (p > 0.05). In the propolis group, the enlargement of hepatocytes, dilatation of canaliculi and the edema regressed. The regenerating and normal hepatocytes were demonstrated. In the TUNEL assay, propolis administration reduced hepatocyte apoptosis. CONCLUSION: Propolis showed a significant hepatoprotective effect in this experimental obstructive jaundice model.

Oxidant status in maternal and cord plasma and placental tissue in gestational diabetes.

The aim of this study was to measure oxidant/antioxidant status in maternal and cord plasma and in placental tissue in gestational diabetes and to correlate the results with the quality of glycemic control of the mother. To achieve this, blood and placental tissue samples have been obtained from pregnant women with gestational diabetes mellitus (GDM) and from the umbilical cord of their fetuses. The same samples have been collected from pregnant women without GDM. In all the samples, oxidant and antioxidant parameters have been studied. It has been observed that the antioxidant defense system was impaired; xanthine oxidase, which is the main free radical-producing enzyme (XO) in the living cells, was activated; and oxidation reactions were accelerated in the samples obtained from patients with GDM. Results suggest presence of oxidant stress in the gestational diabetes, the reason probably being impaired antioxidant defense mechanism and increased free radical production through XO activation.

Human cytochrome c oxidase isoenzymes from heart and skeletal muscle; purification and properties.

Human cytochrome c oxidase was isolated in an active form from heart and from skeletal muscle by a fast, small-scale isolation method. The procedure involves differential solubilisation of the oxidase from mitochondrial fragments by laurylmaltoside and KCl, followed by size-exclusion high-performance liquid chromatography. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate showed differences between the subunit VI region of cytochrome c oxidases from human heart and skeletal muscle, suggesting different isoenzyme forms in the two organs. This finding might be of importance in explaining mitochondrial myopathy which shows a deficiency of cytochrome c oxidase in skeletal muscle only. In SDS polyacrylamide gel electrophoresis most human cytochrome c oxidase subunits migrated differently from their bovine counterparts. However, the position of subunits III and IV was the same in the human and in the bovine enzymes. The much higher mobility of human cytochrome c oxidase subunit II is explained by a greater hydrophobicity of this polypeptide than of that of the subunit II of the bovine enzyme.

Bovine cytochrome c oxidases, purified from heart, skeletal muscle, liver and kidney, differ in the small subunits but show the same reaction kinetics with cytochrome c.

(1) Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate of purified cytochrome c oxidase preparations revealed that bovine kidney, skeletal muscle and heart contain different cytochrome c oxidase isoenzymes, which show differences in mobility of the subunits encoded by the nuclear genome. No differences in subunit pattern were observed between the oxidase preparations isolated from kidney and liver. (2) The kinetics of the steady-state reactions between bovine ferrocytochrome c and the four types of bovine cytochrome c oxidase preparation were compared under conditions of both high- and low-ionic strength. Also the pre-steady-state kinetics were studied. Only minor differences were observed in the electron-transfer activity of the isoenzymes. Thus, our experiments do not support the notion that the subunits encoded by the nuclear genome act as modulators conferring different activities to the isoenzymes of cytochrome c oxidase. (3) The cytochrome c oxidase preparation from bovine skeletal muscle was found to consist mainly of dimers, whereas the enzymes isolated from bovine kidney, liver and heart were monomeric.

The effect of detergents on bovine cytochrome c oxidase: a kinetic approach.

(1) Investigation of the relationship between the detergent concentration and steady-state and pre-steady-state kinetics of cytochrome c oxidase proved to be a valid approach in the study of protein-detergent interaction. (2) Laurylmaltoside, sodium cholate and Triton X-100 influenced the kinetics of cytochrome c oxidase cooperatively at detergent concentrations near their critical micelle concentration. This mode of interaction reflects disaggregation of the oxidase as a result of cooperative binding of the detergent. (3) Addition of increasing concentrations of Tween-80 to the aggregated enzyme caused a more gradual decrease in aggregation of the oxidase, which did not result in a change in activity of the enzyme. This suggests that aggregation of cytochrome c oxidase occurs in a highly regular manner in which no catalytic sites are shielded off. (4) Oxidase aggregates present at detergent concentrations below the critical micelle concentration of laurylmaltoside and Triton X-100 showed considerable activity. Their kinetics were equal to those of the oxidase in Tween-80, suggesting that the protein molecules are aligned in a similar way in all oligomers. Aggregates present in low concentrations of sodium cholate showed turnover rates that were twice as low as those observed with other aggregates. (5) Solubilisation of the oxidase by sodium cholate or Triton X-100 resulted in almost complete inhibition of enzymic activity, whereas the association rate of ferrocytochrome c was almost equal to that found for monomeric oxidase in laurylmaltoside. These results are in agreement with a mixed-type inhibition.

A potential role for nitric oxide pathway in tuberculous pleural effusion.

SETTING: Tuberculous pleural effusion leads to an immune response involving mainly immune and mesothelial cells. Nitric oxide (NO) produced by these cells may have antimycobacterial effects against Mycobacterium tuberculosis. OBJECTIVE: To investigate the possible role of NO in connection with the arginase enzyme, which controls the synthesis of NO through arginine depletion. DESIGN: Pleural fluid samples from 20 patients with tuberculous pleural effusion were used for arginase activity and NO level determination. Results were compared with those from 12 lung cancer, 12 pneumonia and 12 congestive heart failure (CHF) patients. RESULTS: Pleural arginase activity in tuberculosis patients was found to be significantly decreased compared to lung cancer and pneumonia groups, while the NO level was higher in tuberculosis patients. All groups except the CHF group had significant correlations between NO level and white blood cell count. Arginase activity and red blood cell count correlated significantly in lung cancer and CHF groups. CONCLUSION: The arginine-NO pathway seems to be involved in the pathogenesis of tuberculous pleural effusion. Decreased arginase activity may cause arginine accumulation, which may then lead to increased NO synthesis by immune and mesothelial cells, reflecting a host defence mechanism.

Adenosine deaminase, 5' nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues.

We determined activities of adenosine deaminase (ADA), 5' nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (Cu-Zn SOD), and catalase (CAT) enzymes in 15 human laryngeal tissues with well-differentiated squamous cell carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal laryngeal tissues. We found lower ADA and 5NT and higher XO, Cu-Zn SOD, and CAT activities in cancerous tissues than those in corresponding noncancerous ones. In the correlation analysis, we established one positive intercorrelation, which was between ADA activities of tumor tissues and noncancerous adjacent tissues. We also found some significant intracorrelations between enzyme activities of the tissues, all of which were positive in cancerous ones.

Adenosine deaminase, 5'nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human bladder tissues.

Activities of adenosine deaminase (ADA), 5'nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (SOD), and catalase (CAT) enzymes were measured in cancerous and cancer-free adjacent bladder tissues from 36 patients with bladder cancer and in control bladder tissues from 9 noncancer patients. Increased ADA and decreased XO, SOD, and CAT activities were found in cancerous bladder tissues compared with those of cancer-free adjacent tissues and of control bladder tissues. Differences were also found between enzyme activities in the bladder of different disease stages and grades. In the cancerous tissues, only positive intracorrelations were found, but in the cancer-free adjacent tissues and control tissues, both positive and negative correlations were established between enzyme activities. Results suggested that purine metabolism and salvage pathway activity of purine nucleotides were accelerated in the cancerous human bladder tissues via increased ADA and decreased XO activities, probably together with changes in some other related enzyme activities and, free radical metabolising-enzyme activities were depressed in cancerous bladder tissues, which indicated exposure of cancerous tissues to more radicalic stress.

Adenosine deaminase, 5'-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients with gastric cancer.

The activities of some of the enzymes participating in nucleotide metabolism were measured in cancerous and noncancerous gastric tissues from patients with gastric cancer. The enzyme activities measured were found to be higher in the cancerous tissues than in the non-cancerous tissues. Adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), guanase (GUA) and cytidine deaminase (CD) activities in the cancerous tissues were 56.0 +/- 24.0, 45.0 +/- 20.0, 0.34 +/- 0.16 and 4.65 +/- 2.04, respectively. The activities in non-cancerous tissues were 13.2 +/- 6.0, 19.8 +/- 8.3, 0.12 +/- 0.06 and 1.65 +/- 0.8, respectively. Cancerous tissues consisted of 7 gastric tissues with Grade I-II and 8 tissues with Grade III-IV adeno cancer. Non-cancerous adjacent tissues were obtained from the same patients with Grade I-II cancer. There were no meaningful differences between enzyme activities of the gastric tissues with Grade I-II and Grade III-IV cancer. Enzyme activity ratios indicates that ADA activity increased by the highest amount relative to other enzyme activities in the cancerous tissues. In the correlation analysis, we found positive correlations between some of the enzyme activities in the cancerous tissues. Results suggest that increased activities of these enzymes might play a part in the accelerated nucleotide metabolism in the cancerous gastric tissues.

The effects of gentamicin on the activities of glutathione peroxidase and superoxide dismutase enzymes and malondialdehyde levels in heart tissues of guinea pigs.

In this study, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels were measured in heart tissues from guinea pigs treated with gentamicin and gentamicin plus vitamin E combination. Mean values were compared with those of the controls treated with only physiological saline solution. The activities of SOD and GSH-Px were found to be lower and the MDA level higher in the hearts from gentamicin-treated animals compared with those of the controls. In the gentamicin plus vitamin E group, however, tissue SOD activity was found to be increased and MDA level decreased significantly relative to the gentamicin group. GSH-Px activity was lowest in this group. Results suggest that gentamicin suppresses SOD and GSH-Px activities in heart tissue, thereby making the tissue more vulnerable to oxidative stress and peroxidative attacks, an important indicator of which is increased MDA level in the heart tissues from gentamicin-treated guinea pigs. This effect might be deleterious when gentamicin is used after cardiac surgery since a potential risk of free radical injury exists in the heart tissue during and/or after cardiac surgery owing to ischaemia and reperfusion processes, and, possibly, in the management of the patients with certain types of heart disease. Our results showed that vitamin E given concomitantly with gentamicin could protect the heart tissue against free radical injury.

The effect of red wine on blood antioxidant potential.

We investigated the effects of red wine on blood antioxidant potential in an attempt to elucidate molecular mechanisms concerning the possible protective role of red wine in atherosclerosis. Volunteer subjects in the study group consumed a standard meal and drank red wine (5 mg/kg) while controls consumed the same meal and drank water. Over 4 1/2 hours, blood samples were taken, and malondialdehyde (MDA) and antioxidant potential (AOP, obtained from MDA levels before and after superoxide radical attack) values were measured in the plasma and erythrocytes. We found that AOP values of plasma and erythrocyte samples from the study group were at their highest after 1 1/2 hours and then declined to basal values at 4 1/2 hours. There were no statistically significant differences between the basal AOP values of the study group and the control group. With regard to MDA levels, gradual increases were seen in the plasma of the control group during the 3 hours after food, but no changes were seen in the plasma of the study group in this period. Although there were increases in erythrocyte MDA levels of both groups over 3 hours, the MDA production rate was significantly higher in the control group. Our results suggest that red wine causes significant increases in AOP values of plasma and erythrocytes, which may prevent cellular peroxidation reactions and lessen atherosclerotic complications through inhibition of LDL.

Comparison of antioxidant potentials of red wine, white wine, grape juice and alcohol.

Antioxidant potential (AOP) and non-enzymatic superoxide radical scavenger activity (NSSA) values of red wine, white wine, grape juice and ethyl alcohol were assessed and values were compared. The effects of these beverages on serum AOP and NSSA values were also measured in vitro. Red wine, white wine and grape juice exert strong antioxidant activity in similar degrees and all produce significant effects on serum AOP and NSSA values. However, ethyl alcohol does not have either AOP or NSSA, nor does it have an effect on serum AOP or NSSA values. AOP values (nmol/ml h) of red wine, white wine and grape juice were 20.8 +/- 4.2, 23.2 +/- 4.0 and 24.6 +/- 4.8, respectively. NSSA values (U/ml) of red wine, white wine and grape juice were 30.4 +/- 6.8, 26.8 +/- 5.6 and 32.6 +/- 5.8, respectively. There were no statistically meaningful differences between AOP and NSSA values of the groups (p > 0.05 for all). Results suggest that red wine, white wine and grape juice all have high antioxidant potential to protect cellular structures against peroxidation reaction owing to their rich phenolic contents.

An unusual central retinal dystrophy associated with ichthyosis vulgaris.

A number of ichthyosis syndromes may have retinal abnormalities such as the retinitis pigmentosa-like diffuse rod-cone dystrophy in Refsum's syndrome and the maculopathy in Sjögren-Larsson syndrome. We present two sisters who have an unusual, almost identical, bilaterally symmetric central retinal dystrophy associated with ichthyosis vulgaris in the absence of other systemic disorders. We believe that this dystrophy has not been previously described in patients with any of the known varieties of ichthyosis.

Bilateral megalocornea with unilateral lens subluxation.

Megalocornea refers to an enlarged cornea that measures 13 mm or more in horizontal diameter in the absence of raised intraocular pressure. We describe a five-month-old boy with bilateral megalocornea with unilateral lens subluxation. No other ophthalmological abnormality was present. In all previously reported cases with megalocornea and ectopia lentis, the lens was cataractous and the dislocation was in the inferior and posterior direction. In contrast, our case had a clear lens which was displaced superonasally.

Pars plana vitrectomy with pars plana tube implantation in eyes with intractable glaucoma.

AIMS: Intractable glaucoma is glaucoma resistant to medical therapy and conventional surgical procedures. In this study, a planned surgical technique is discussed for controlling the increased intraocular pressure in selected cases with intractable glaucoma. METHODS: Total pars plana vitrectomy with pars plana tube implantation was performed in 17 eyes of 17 cases with intractable glaucoma. Patients with neovascular glaucoma were not included in this study. The mean age of these patients (seven men, 10 women) was 44.6 (SD 22.1) years and mean follow up period was 30.3 (15.5) months (range 4-71). Drainage implants with a disc were used in 16 cases, whereas, a tube with scleral buckle (Schocket surgery) was preferred in one case. An intraocular pressure below or equal to 20 mm Hg without any adjunctive medication or with only one type of antiglaucomatous drop was considered as an adequate operative outcome. RESULTS: 16 out of 17 eyes maintained adequate pressure control. Only three out of these 16 eyes required prophylactic antiglaucomatous medications. One patient underwent reoperation for pressure control. The most severe complications observed postoperatively were intravitreal haemorrhage (one case), choroidal detachment (one case), implant failure (one case), total retinal detachment (two cases), and corneal endothelial decompensation (five cases). CONCLUSION: Pars plana placement of drainage tube following pars plana vitrectomy should be considered as an alternative method for controlling increased intraocular pressures in selected patients with intractable glaucoma.

Malignant melanoma of the optic nerve head in a case of oculodermal melanocytosis.

Malignant melanoma of the uveal tract, orbit, and brain have been reported to occur in patients with oculodermal melanocytosis. A 60-year-old Caucasian man with oculodermal melanocytosis developed a malignant melanoma of the optic nerve head in the left eye. This case is the first reported example of a malignant melanoma developing in the optic nerve associated with oculodermal melanocytosis. After presentation the patient refused surgery for 19 months and the progression of the tumour necessitated an exenteration of the orbit.