Non steroidal antiinflammatory drugs may be harmful to normal kidneys: experimental surgery model*.

BACKGROUND AND AIM: The exact effect of analgesics on normal kidneys is not known yet. We aimed to evaluate the impression of non steroidal antiinflammatory drugs (NSAID) used post-operatively on kidneys, in rat (tracheotomy) model. METHODS: Twenty-five non-uremic male wistar albino rats were included. For 18 rats, tracheotomy was performed and divided into two groups. First group, NSAID (diclofenac 10 mg/kg/day intramuscular (im)) (NSAID, n=8); second group isotonic (im)(Control, n=10) were administered for a week. For third group (Histological control,n=7) in order to evaluate normal histology neither surgery nor medication were applied. At the end (7th day), 24 hours urine collected then, blood samples were taken by intracardiac punction and were sacrified. One of the kidneys fixed for histological evaluation, the other was preserved for the measurements of tissue enzyme levels. Lipid peroxidation products and antioxidant enzyme levels were measured both from plasma and renal tissues. Histologically inflammation, regeneration, degeneration assessed semiquatitativelly and immunohistochemical dyes were applied. RESULTS: Hemoglobin thiobarbituric acid reactive substance level indicating the increase of lipid peroxidation in NSAID group was higher than control group (673±204 vs.373±27nmol/gHb respectively, p>0.05). Superoxide dismutase (one of the antioxidant enzymes responsible for reduction of reactive oxygen substances) and serum nitrate levels were lower in NSAID groups (700±68 vs.1371±164U/gHb and 26±4.4 vs.50.8±6.8 µmol/mL respectively, p<0.05).Although tissue levels were parallel to plasma levels but the difference wasn't significant. In histological assessment degeneration was present only in NSAID group (1.3±0.6 vs.0.0±0, p<0.05). Inflammation were lower than the control group (0.8±0.4 vs.1.2±0.2, p>0.05). Cyclooxygenase-2 expression was disappeared in NSAID group. CONCLUSIONS: NSAIDs mostly used post-operatively for analgesia, may cause unfavorable effects on kidneys by oxidative stress.

A monocentric pilot study of an antioxidative defense and hsCRP in pediatric patients with glycogen storage disease type IA and III.

BACKGROUND AND AIMS: Patients with glycogen storage disease type Ia (GSD Ia) and III (GSD III) do not develop premature atherosclerosis despite hyperlipidemia. The aim of the study was to investigate the oxidative-antioxidative conditions and high sensitivity C-reactive protein (hsCRP) levels in patients with glycogen storage disease type Ia and III. METHODS: We measured lipid profile and lipid peroxidation products in comparison with hsCRP and antioxidative status: trolox equivalent antioxidant capacity, total antioxidant activity, proteinaceous antioxidant enzymes (catalase, superoxide dismutase, paraoxonase, arylesterase), aqueous antioxidants (vitamin C, uric acid, bilirubin, total protein) and lipid-soluble antioxidants (alpha-tocopherol, beta-carotene). The study included 50 individuals: 22 with GSD Ia, 9 with GSD III, and 19 healthy subjects. RESULTS: GSD Ia patients showed a marked hypertriglyceridemia, whereas GSD III patients demonstrated hypercholesterolemia with elevated LDL-cholesterol and decreased HDL-cholesterol levels. Lipid peroxidation levels increased in both GSD groups. The antioxidant activity elevated in GSD Ia group. No significant differences were found in the activities of antioxidant enzymes. Uric acid and alpha-tocopherol levels increased, however, vitamin C and beta-carotene reduced in both GSD groups. The hsCRP levels did not differ among the groups. CONCLUSIONS: In summary our study revealed normal levels of hsCRP in spite of the dyslipidemic status in both GSD patients. The increased plasma antioxidative defense in GSD Ia might be attributed not only to the elevated uric acid but also to the supplemented vitamin E levels. These findings should motivate further investigations in the area of atherosclerotic escape of GSDs.

Broad-band ultraviolet B phototherapy is associated with elevated serum thiobarbituric acid reactive substance and nitrite-nitrate levels in psoriatic patients.

BACKGROUND: Although the local anti-inflammatory, immunosuppressive and oxidative activity of UVB is known, the systemic effect of UVB phototherapy in dermatological patients has not been investigated. OBJECTIVE: We aimed to investigate the lipid peroxidation status (as represented by thiobarbituric acid reactive substance, TBARS) and nitrite-nitrate levels in psoriatic patients under broad-band ultraviolet B (BB-UVB) phototherapy in order to determine the systemic effects of UVB. SUBJECTS AND METHODS: Thirty-two psoriatic patients and 20 healthy controls were included. Blood samples were obtained at the beginning, after 6-10 exposures to BB UVB phototherapy (mean 5 weeks) and at the end of the therapy period (mean 21 weeks). Serum TBARS and nitrite-nitrate levels were evaluated. RESULTS: There was no statistically significant difference in serum TBARS and nitrite-nitrate levels between psoriatic patients (basal) and healthy volunteers. There was no statistically significant correlation between disease duration, disease severity, or the total cumulative dose of UVB and serum levels of TBARS and nitrite-nitrate in psoriatic patients. Total nitrite levels in samples obtained during and at the end of therapy were significantly higher than basal levels (P=0.033 and P=0.005, respectively). TBARS levels in samples obtained during and at the end of therapy were significantly higher than basal levels (P=0 and P=0.026, respectively). There was a negative correlation (r=-0.576, P=0.039) between the total nitrite and TBARS levels in psoriatic patients at the end of therapy. CONCLUSION: Our study showed that chronic exposure to UV irradiation may lead to a systemic effect on lipid peroxidation and NO levels, which are shown by a significant elevation in TBARS and nitrite-nitrate levels in serum.

Atorvastatin improves peritoneal sclerosis induced by hypertonic PD solution in rats.

BACKGROUND: Peritoneal sclerosis is a complication of peritoneal dialysis and results in ultrafiltration failure. It is related to chronic peritoneal injury due to dialysis solution content and recurrent peritonitis. Statins have anti-inflammatory properties which may be of value in modulating responses to injury. We evaluated the capacity of atorvastatin to modify peritoneal alterations secondary to hypertonic glucose. METHODS: Thirty-two non-uremic rats were divided into three groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and group III received hypertonic PD solution (10 ml/day) plus 80 mg/L atorvastatin in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-beta 1 and VEGF levels were determined. RESULTS: Administration of atorvastatin resulted in preserved UF (4.9+/-0.8 vs 7.5+/-0.6 mL, p <0.01), protein loss (2.2+/-0.2 vs 2.1+/-0.1 g/L, p >0.05), and peritoneal thickness (53+/-3 vs 26+/-4 microm, p <0.01). D 1 /D 0 glucose was significantly reduced in the dextrose group (0.70+/-0.02 vs 0.56+/-0.04, p <0.01). Both higher levels of TGF-ss 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group. CONCLUSION: Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of atorvastatin led to prevention of these alterations. We suggest that the anti-inflammatory properties of statins are useful in providing protection of the peritoneal membrane from the effects of hypertonic glucose.

Effect of thyroid function on LDL oxidation in hypothyroidism and hyperthyroidism.

Oxidized low-density lipoproteins (LDL) are highly suspected of initiating the atherosclerosis process. Hypothyroidism is frequently associated with hypercholesterolemia and carries increased risk for atherosclerosis. In contrast to hypothyroidism, hyperthyroidism is not associated with increased LDL cholesterol, but is associated with increased oxidized LDL. This study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism or hyperthyroidism, and to reveal the effects of treatment in hypothyroidism and hyperthyroidism on LDL oxidation and lipid profiles. Thirty-two patients with hypothyroidism and 16 patients with hyperthyroidism were studied before the therapy and thereafter, when they were euthyroid with appropriate treatment. Plasma lipids and lipoproteins, and the oxidizability of LDL by determining the levels of malonaldehyde bis (dimethyacetyl) (MDA) and diene conjugation, were determined at baseline and after the patients were rendered euthyroid. The actual content of dienes in LDL particles was increased in hypothyroidism, with a decrease after T4 supplementation (p < .001). Dienes in LDL particles were increased in hyperthyroidism, with a decrease after treatment (p < .05). In hypothyroid patients, the lag phase was shorter in the pretreatment period than in the euthyroid period (p > .05). The lag phase of hyperthyroid patients was shorter in the pretreatment period than in the euthyroid period and hypothyroid state (p < .001). The Cu2+-catalyzed dienes of LDL and MDA oxidation in the hypothyroid state and the subsequent euthyroid states were decreased (p < .001). The Cu2+-catalyzed dienes of LDL (p < .01) and MDA oxidation (p < .001) in hyperthyroid patients after treatment were decreased. The enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.

Erythrocyte superoxide dismutase, catalase activities and plasma nitrite and nitrate levels in patients with Behçet disease and recurrent aphthous stomatitis.

Behçet disease (BD) and recurrent aphthous stomatitis (RAS) are two distinct diseases of unknown aetiology which are both characterized by oral aphthae. The aim of this study was to determine the possible association of both diseases with antioxidant status and nitric oxide levels. Twenty-six patients (17 female, nine male) with RAS, 28 patients (17 female, 11 male) with BD and 31 (22 female, nine male) healthy control subjects were included in the study. Blood samples were studied for erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities and plasma nitric oxide (NO) levels. Erythrocyte SOD activity in BD patients was significantly higher than in RAS patients and controls. Although SOD activity in RAS patients was higher than in controls, the difference was not statistically significant. No significant differences in CAT activities or NO levels were found between the three groups. In conclusion, changes in SOD activity may be important in the inflammatory reactions observed in BD and RAS, but NO does not seem to play a primary role in the aetiopathogenesis.

Effect of organophosphate intoxication on human serum paraoxonase.

Recently, interindividual variations in serum paraoxonase (PON1) activity and the differences in its metabolic activity towards different organophosphates (OPs) caused by the coding region polymorphisms L55M and Q192R have been found to be important risk factors in susceptibility to OP poisoning. In this study, we investigated the effect of PON1 on the outcome of acute OP intoxication and the effect of acute OP intoxication on PON1. Twenty-eight OP-poisoned patients and 66 healthy volunteers were studied. Patients were evaluated for the clinical manifestations of OP intoxication as well as PON1 activity, PON1 mass and PON1 polymorphisms. Butyrylcholine-esterase (BChE) activity was 50% lower (2,276 +/- 738 U/L versus 5,037 +/- 1,553 U/L, P<0.01) while PON1 activity was 30% lower [114.2 +/- 67.4 nmol/mL/min versus 152.9 +/- 78.9 nmol/mL/ min, P<0.05) in patients than in controls. We observed that the PON1 and BChE activities of eight of the original subjects returned to normal levels when they were reinvestigated six months after exposure. The frequency of the PON192Q allele was significantly higher in patients than controls (85.7% versus 59.7%, chi2=6.745, P=0.034). QQ/ MM individuals had the lowest activity towards paraoxon, while RR/LL individuals had the highest activity. Our data indicate that interindividual differences in PON1 activity and the PON1-55 and -192 polymorphisms are important risk factors in susceptibility to acute OP poisoning; therefore, identifying an individual's PON1 alloenzymes may play an important role in the treatment of patients suffering from OP intoxication.

Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may implicate poor glycemic control.

BACKGROUND: Previous studies suggest that elevated oxidative stress implicates poor glycemic control resulting in the development of diabetic complications. By evaluating the relationship between paraoxonase (PON) and antioxidant enzyme activities and glycemic control in diabetic patients with and without complications, we investigated whether there is a role of PON and/or antioxidant status in glycemic control. METHODS: A total of 107 patients with type 2 diabetes mellitus (DM) was included in the study. Seventy-five patients had complications including microangiopathy, proliferative retinopathy, and/or nephropathy while 32 had no complications. The control group consisted of 29 age- and sex-matched healthy persons. Serum superoxide dismutase (SOD) and catalase activities were measured according to Sun and Goth, respectively. Basal and salt-stimulated paraoxonase activities and arylesterase activity were determined using the method of Eckerson et al. RESULTS: There was an increase in the catalase activity and a decrease in the basal and salt-stimulated PON activity of patients when compared with controls, while no significant difference was observed in SOD activity. PON phenotypes had no effect on any parameter in patient and control groups. The ratio of catalase/SOD was 2.44 +/- 7.10 and 0.17 +/- 0.09 in diabetics and controls, respectively (p = 0.004); this was associated with an elevation in HbA1c levels. On the other hand, catalase/PON ratio was also enhanced in diabetic patients (2.8 +/- 5.2), showing a relationship with HbA1c levels compared to controls (0.29 +/- 0.3, p = 0.000). CONCLUSIONS: The data of this study reveal that enhanced catalase/SOD and catalase /PON ratios that are correlated with HbA1c levels are observed in diabetic patients; thus, these ratios may be used as markers of poor glycemic control and as risk factors in the development of diabetic complications.

Antioxidant enzymes and paraoxonase show a co-activity in preserving low-density lipoprotein from oxidation.

Oxidative modification of low-density lipoprotein in the artery wall plays a crucial role in the development of atherosclerosis. This physiopathological mechanism is clearly inhibited by high-density lipoprotein possibly via paraoxonase enzyme activity, present in high-density lipoprotein. In this study, we determined the in vitro susceptibility of low-density lipoprotein to oxidation and the effect of various factors, such as paraoxonase phenotypes, on this process. Low-density lipoprotein from healthy volunteers (n=66) was isolated using the precipitant reagent and the oxidation was evaluated by measuring the malonyl dialdehyde and diene levels. Low-density lipoprotein cholesterol and phospholipid, vitamin E, serum cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels, and erythrocyte antioxidant enzymes were also determined. There was no difference among the parameters with regard to gender. Low-density lipoprotein samples obtained from subjects with the AA allele were more prone to oxidation, as observed by their higher stimulated conjugated diene (P=0.041) and thiobarbituric acid-related substance (P=0.042) levels, than samples from subjects with AB or BB alleles. The subjects with the BB allele had higher superoxide dismutase (P=0.021) and catalase (insignificant increase) activities, while their conjugated diene (P=0.000) levels were lower. In conclusion, our results revealed that the high low-density lipoprotein oxidation is related to the high low-density lipoprotein cholesterol content and low phospholipid content. The present study demonstrated an increase in superoxide dismutase and catalase activities, as well as PON1 activities, in subjects with the BB allele. Since these enzymes all show activity against low-density lipoprotein oxidation, we propose that future investigations on atherosclerotic processes should address PON1 polymorphism as well as PON1 and other antioxidant enzymes.

The effects of melatonin on the antioxidant systems in experimental spinal injury.

Melatonin has been recently shown by various in-vivo and in-vitro studies to exert potent neutralising effects on hydroxyl radicals, stimulate glutathione peroxidase (GSH-Px) activity, and protect catalase (CAT) from the destructive activity of hydroxyl radicals in neural tissue. We aimed to investigate the possible effects of pharmacological dose of melatonin on some of the antioxidant defence systems in an in-vivo study of experimental spinal injury. Seven groups of adult male Sprague Dawley rats were used in the following scheme: Group I: Naive (n = 6), Group II: Lesion (n = 8), Group III: Melatonin (n = 5), Group IV: Melatonin + Lesion (n = 8), Group V: Placebo + Lesion (n = 5), Group VI: Sham operation (n = 5), and Group VII: Placebo (n = 5). Experimental spinal injury was induced at level T7-T8 by 5 sec compression of the total cord with an aneurysm clip on anaesthetised and laminectomized animals. The total 10 mg/kg dose of melatonin (Sigma) dissolved in alcohol-water was administered i.p. four times in 2.5 mg/kg doses, at 20 min pre-, at the time of and at 1 h and 2h post-compression. At 24 +/- 2h post-injury, the rats were euthanized and the lesioned segments of cord were dissected and homogenised with special care taken to distribute equal amount of injured tissue in each sample for analysis of reduced glutathione (GSH), oxidised glutathione (GSSG), superoxide dismutase (SOD), and CAT activity. Compression injury decreased GSH/GSSG ratio significantly (p < .0001). Melatonin, by itself, significantly decreased GSSG content (p < .05) and increased CAT activity (p < .05) in the naïve rats. Melatonin treatment decreased GSSG activity, thus elevating GSH/GSSG ratio, and also increased SOD and CAT activity without reaching statistical significance in the lesioned animals. In conclusion, pharmacological dose of systemically applied melatonin seemed to support some features of the antioxidant defence systems in our hands.

Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine.

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.

Catalase and paraoxonase in hypertensive type 2 diabetes mellitus: correlation with glycemic control.

OBJECTIVES: Type 2 diabetes mellitus (DM) is well recognized as being associated with increased prevalence of hypertension. Experimental and epidemiologic studies have shown that oxygen-free radicals are elevated because antioxidant enzyme activities are altered both in uncontrolled essential hypertension and DM itself. Recently paraoxonase (PON) has been recognized as an antioxidant enzyme that hydrolyzes lipid peroxides. The aim of this study is to evaluate simultaneously PON activities and antioxidant status in hypertensive type 2 DM cases and to establish any possible relationship between these parameters and duration of hypertension or diabetes, hemoglobin (Hb) A1c levels, and lipid parameters. DESIGN AND METHODS: Nineteen normotensive subjects with type 2 DM, 37 hypertensive (diastolic blood pressure 90 mm Hg or more) subjects with type 2 DM, and 25 normotensive control subjects with normal glucose tolerance were selected for this study. Superoxide dismutase (SOD), catalase, and basal-stimulated PON activities were measured by the methods of Sun et al.; Goth; and Eckerson, Wyte, and La Du, respectively; other lipid parameters were determined using an autoanalyzer. RESULTS: Catalase activities of either hypertensive patients with type 2 DM or type 2 DM patients without complication were found to be higher than controls (p<0.01), although no significant difference in SOD and basal-stimulated PON activities was observed between these groups. A significant elevation in catalase activity (p = 0.004) of patients with high HbA1c levels (>7.0%) (n = 37) compared with patients with low HbA1c levels (<7.0%) (n = 19) was detected. There was also a positive correlation between the catalase activities and fasting glucose levels and HbA1c concentrations in hypertensive patients with type 2 DM (r = 0.4567, p<0.05 and r = 0.3686, p<0.05, respectively). An increase in catalase activity of patients with B and/or AB phenotype compared with patients with A phenotype was also noted. CONCLUSION: Poor glycemic control in diabetes is strongly associated with an increase in free radicals and consequent diabetic complications. Uncontrolled glucose metabolism may also be the cause of alterations in antioxidant enzymes. Among these, catalase correlates best with poor glycemic control. The current data reveal that B allele carriers of PON are more susceptible to oxidant stress.

Paraoxonase and acetylcholinesterase activities in humans exposed to organophosphorous compounds.

Different kinds of organophosphorous compounds (OP) are used as pesticides in Turkish agriculture. Suicidal, accidental, or occupational exposure may occur in developing countries. OP inhibit acetylcholinesterase (AChE) activities; on the other hand, serum paraoxonase (PON1) hydrolyzes the toxic metabolites of a variety of OP. In recent years, some studies have shown that PON1 activity is an important marker in individuals who are exposed to OP. Both serum cholinesterase and PON1 activities were measured spectrophotometrically from 18 male agricultural workers who were chronically exposed to azinphos methyl, chlorpyriphos, or malathion and other pesticides during cereal spraying, transportation, and storage. The individuals were classified according to PON1 phenotypes using the antimode 60% stimulation method to determine the dividing point between non-salt-stimulated, A type (homozygotes for the low-activity allele), and salt-stimulated AB (heterozygotes) and B types (homozygotes for the high-activity allele). A positive correlation was found between AChE activities and percent of PON1 stimulation. The individuals with phenotype A had the lowest enzyme activities. This study suggests that individuals with phenotype A might be more sensitive to OP-induced toxicity.

Effect of N-dicyclopropylmethyl-amino-2-oxazoline (S-3341) on antioxidant status and nitric oxide in hypertensive patients.

Defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of nitric oxide (NO) or increased production of free radicals, mainly the superoxide anion, may facilitate the development of an arterial functional spasm. Although it has been shown that many antihypertensive drugs can normalise both the antioxidant activity and NO, the antioxidant effect of N-dicyclopropylmethyl-amino-2-oxazoline (S-3341), an alpha-adrenoreceptor agonist, has not been investigated. In this study we investigated the antioxidant and NO status in hypertensive patients and whether there was any effect of S-3341 on these parameters. Eleven patients with mild hypertension (mean systolic blood pressure 159.5 +/- 2.5 mmHg) were administered S-3341 (1 mg/day) for 4 weeks. Plasma vitamin E, nitrite-nitrate and MDA levels, and catalase activity, were measured both before and after treatment with S-3341. There was significant reduction in both mean systolic and diastolic blood pressure during the treatment. We found an increase in catalase activity (p < 0.05), a decrease in malondialdehyde (MDA) levels (p < 0.01) and an insignificant increase in vitamin E levels in hypertensive patients following the S-3341 treatment. We propose that S-3341 may prevent oxidant stress in hypertensive patients by inhibiting free-radical formation.

Effect of vitamin E on antioxidant enzymes and nitric oxide in ischemia-reperfused kidney injury.

The effects of Vitamin E administration on antioxidant enzyme activities and nitrite-nitrate levels of the reperfused rat kidney tissues were investigated by performing a 60 min ischemia followed by 24 and 72 hours of reperfusion. Vitamin E administration or the placebo (SF) was applied as 100 mg/kg BW. As expected, catalase (CAT) (p<0.05) and superoxide dismutase (SOD) (p<0.05) activities of ischemia/reperfused (I/R) kidney tissue were lower and malondialdehyde (MDA) levels were higher than control kidneys in both SF and vitamin E treated groups following 24 h reperfusion. During reperfusion of long term (72 h), vitamin E triggered a decrease in the MDA levels in the ischemic tissue, while it did not provoke a significant effect on SOD and catalase activities. Total nitrite levels of ischemic tissues in both of the groups were higher than matched control kidneys and this elevation was more clear in the vitamin E treated group. Our results showed that vitamin E has a protective effect on I/R injury, by a direct chain breaking effect on lipid peroxidation (LPO) and hence preventing the nitric oxide (NO) reservoir of ischemic tissue. Alfa-tocopherol may be a promising agent for the prevention of tissue injury caused by free oxygen radicals.

Possible supportive effects of co-dergocrine mesylate on antioxidant enzyme systems in aged rat brain.

Free radical damage is implicated in the course of many diseases, including age-related dementias. Oxidative deamination of primary monoamino oxidase (MAO) produces NH3 and H2O2 with established or potential toxicity. MAO activity is increased in aged rat brain and significantly lowered by chronic hydergine (codergocrine mesylate, Sandoz) treatment. The aim of this study was to investigate the effects of hydergine on enzymatic antioxidant defense systems. Hydergine or vehicle was administered systemically to young (3 months) and aged (18 months) Sprague-Dawley rats for 20 days and 24 h after the termination of the treatment, superoxide dismutase (SOD) and catalase (CAT) activities were determined in some brain regions. SOD and CAT activities were higher in the aged animals and were further increased with hydergine treatment. The increase in SOD levels caused by hydergine treatment in the aged animals were the most prominent in the hippocampus and in the corpus striatum. There was no region-specific effect of hydergine treatment on CAT levels in aged animals. The possible causal relationship between increased MAO activity, a generator of free radicals, and increased antioxidant defense in aging brain require further investigation. Decreasing MAO levels and supporting the antioxidant enzymes may underlie the efficacy of hydergine in the treatment of age related cognitive decline.

Sex differences in nitrite/nitrate levels and antioxidant defense in rat brain.

This study assessed sex differences in stable metabolites of nitric oxide and major enzymes involved in antioxidant defense in various regions of rat brain. Nitrite/nitrate levels and activities of superoxide dismutase and catalase were determined in cortex, hippocampus, corpus striatum, midbrain and cerebellum of adult male and female Sprague-Dawley rats. Nitrite/nitrate levels were significantly higher in the cortex and the hippocampus of male than female rats, while catalase activity was higher in the cortex of females than in males. These sex differences may have significant effects on brain function in health and disease.

The endogenous scavengers in cerulein-induced acute pancreatitis.

Studies in animal models suggest that oxygen radicals are important in the pathogenesis of acute pancreatitis. Cerulein, a decapeptide isolated from the skin of the frog, Hyla caerula, is closely related to the C-terminus of cholecystokinin and it is a potent stimulant of pancreatic exocrine secretion. The aim of the present study was to measure the activity of endogenous scavengers, superoxide dismutase, catalase and glutathione levels in cerulein-induced acute pancreatitis in rats. We found that the plasma amylase and ribonuclease levels in the pancreatitis group were both significantly high (p < 0.01, p < 0.05, respectively) when compared with the control group. Although superoxide dismutase and glutathione levels of pancreatic tissue were decreased significantly (p < 0.01, p < 0.01 respectively), we observed a significant increase (p < 0.01) in catalase activity in the cerulein treated group compared to the control group. Therefore, we concluded that the profound alteration of the activities of endogenous scavengers (superoxide dismutase, catalase) and glutathione depletion occurring after cerulein-induced pancreatitis seemed to be important in tissue injury and may provide the basis for successful therapy of the disease.