Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity1

Embryonic bioactivation and formation of reactive oxygen species (ROS) are implicated in the mechanism of phenytoin teratogenicity. This in vivo study in pregnant CD-1 mice evaluated whether maternal administration of the antioxidative enzymes superoxide dismutase (SOD) and/or catalase conjugated with polyethylene glycol (PEG) could reduce phenytoin teratogenicity. Initial studies showed that pretreatment with PEG-SOD alone (0.5–20 KU/kg IP 4 or 8 h before phenytoin) actually increased the teratogenicity of phenytoin (65 mg/kg IP on gestational days [GD] 11 and 12, or 12 and 13) (p < .05), and appeared to increase embryonic protein oxidation. Combined pretreatment with PEG-SOD and PEG-catalase (10 KU/kg 8 or 12 h before phenytoin) was not embryo-protective, nor was PEG-catalase alone, although PEG-catalase alone reduced phenytoin-initiated protein oxidation in maternal liver (p < .05). However, time-response studies with PEG-catalase (10 KU/kg) on GDs 11, or 11 and 12, showed maximal 50-100% increases in embryonic activity sustained for 8-24 h after maternal injection (p < .05), and dose-response studies (10–50 KU/kg) at 8 h showed maximal respective 4-fold and 2-fold increases in maternal and embryonic activities with a 50 KU/kg dose (p < .05). In controls, embryonic catalase activity was about 4% of that in maternal liver, although with catalase treatment, enhanced embryonic activity was about 2% of enhanced maternal activity (p < .05). PEG-catalase pretreatment (10-50 KU/kg 8 h before phenytoin) also produced a dose-dependent inhibition of phenytoin teratogenicity, with maximal decreases in fetal cleft palates, resorptions and postpartum lethality at a 50 KU/kg dose (p < .05). This is the first evidence that maternal administration of PEG-catalase can substantially enhance embryonic activity, and that in vivo phenytoin teratogenicity can be modulated by antioxidative enzymes. Both the SOD-mediated enhancement of phenytoin teratogenicity, and the inhibition of phenytoin teratogenicity by catalase, indicate a critical role for ROS in the teratologic mechanism, and the teratologic importance of antioxidative balance.     

Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats

When exposed continuously to hyperoxia (100% O2, 760 Torr barometric pressure), rats pretreated with polyethylene glycol (PEG)-attached superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 + 7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative edematous lung injury, as assessed by increases in lung oxidized glutathione (GSSG) contents, pleural effusions, and lung lavage albumin concentrations than saline-pretreated rats. Rats pretreated with the long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or PEG-albumin also had decreased acute oxidative edematous lung injury compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or saline. In vitro studies suggested that PEG itself may have contributed to protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.) or H2O2. Compared with more effective endogenous (via preexposure to hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant enzymes, PEG enzymes are less protective against lung injury from continuous hyperoxia.     

H2O2 mediates O2 toxicity in cultured fetal rat distal lung epithelial cells.

It is unknown which of the reactive oxygen species is primarily responsible for the cytotoxicity of 95% O2 for rat distal fetal lung epithelial cells in vitro. Incubation of cells with 25 U/ml polyethylene glycol (PEG)-conjugated SOD and 50 U/ml PEG-catalase, but not PEG-SOD or SOD mimics alone, significantly reduced 95% O2-mediated cytotoxicity. Liposome-entrapped catalase, without SOD, also significantly reduced 95% O2-mediated cytotoxicity. Increased formation of lipid hydroperoxides, as assessed by the formation of 8-isoprostane and aldehydes, was attenuated by both 100 microM Trolox, a vitamin E analogue, and by 5 microM U74389G, an amino steroid. Trolox, but not U74389G, prevented an increase in cell-derived H2O2, hydroxyl radical and 95% O2-mediated cytotoxicity. An increase in hydroxyl radical formation, but not cell death, observed in 95% O2, was prevented by 0.1 microM phenanthrolene, a cell permeant iron chelator. DNA extracts of rat distal fetal lung epithelial cells maintained under serum-free conditions had an electrophoretic pattern consistent with some degree of apoptosis. However, no increase in laddering was seen with exposure to 95% O2. These data are consistent with hydrogen peroxide, but not lipid hydroperoxides or hydroxyl radical, being a critical effector of O2-mediated necrotic cell death in distal lung epithelial cells.     

The effects of oxygen free radicals on the preserved kidney

This study evaluated the effect of specific scavengers of oxygen derived free radicals on the results of kidney preservation. The immediate function of rabbit kidneys preserved for 24 hr by hypothermic perfusion was studied on an ex vivo shunt. A significant improvement in creatinine clearance was seen when the perfusate was treated with superoxide dismutase (SOD) and catalase (CAT), with values of 261 ± 82 ml/hr vs control values of 203 ± 72 ml/hr, P < 0.05. This effect was enhanced if a long-persistent polyethylene glycol-linked form of SOD, namely PEG-SOD, was used (330 ± 58 ml/hr, P < 0.01). Recipient treatment and other modifications designed to protect against free radicals resulted in similar improvement in function. In contrast, no effect of free radical scavengers could be demonstrated in kidneys which were preserved by flush cooling, whether the agents were added to the flushing solution, given to the recipient, or both.     

Effect of ethanol in vivo on enzymes which detoxify oxygen free radicals

The effects of ethanol administered as a 15% solution in drinking fluid on weight gain, soluble liver protein and the activity of the three enzymes of oxygen radical metabolism (i.e., superoxide dismutase, catalase, and glutathione peroxidase) were studied in five inbred strains of mice (129/ReJ, BALB/c, C3H/HeSnJ, C57BL/6J, Csb) and Sprague Dawley rats, relative to age, sex, and genotype matched controls. Animals maintained on ethanol exhibited lower weight gains and elevation of soluble liver protein than controls. Total superoxide dismutase, catalase and glutathione peroxidase activity in ethanol-treated animals were in general reduced in comparison to that of their matched controls, with each strain showing genotype specific enzyme activity. Such ethanol feeding results are attributed to the direct and indirect effects of this treatment protocol and raise the possibility that ethanol-fed animals may be susceptible to free radical damage and at least some of the cellular damages observed following ethanol challenges could be attributed to the reduced level of these protective enzymes.     

Effects of growth hormone on hypothalamic catalase and Cu/Zn superoxide dismutase

Age-associated changes in hypothalamic catalase activity and level, and Cu/Zn superoxide dismutase (Cu/Zn SOD) activity were examined in Ames dwarf mice with growth hormone (GH) deficiency and prolonged lifespan, in PEPCK-hGH transgenic mice with overexpression of GH and reduced lifespan, and compared to values measured in normal controls. Hypothalami from young (3-4 months), middle-aged (9-10 months), and old (19-23 months) male mice were examined using spectrophotometric assay and Western blot. In dwarf mice, Cu/Zn SOD and catalase activities declined with age, and were higher than the corresponding normal values in young and middle-aged groups. Catalase levels also declined with age, but were similar to values in normal controls. In GH transgenic mice, age-associated decline of both catalase and Cu/Zn SOD occurred earlier than in normal animals. Catalase levels and activities in transgenic animals were similar to controls, whereas Cu/Zn SOD activity was higher in transgenics than in normal mice. The present results suggest that dwarf mice, during early life, have enhanced hypothalamic free radical defenses, which may contribute to their extended lifespan. However, from the present results in GH transgenic mice, it is impossible to conclude whether early decline of hypothalamic catalase and Cu/Zn SOD in these animals represents a correlate of accelerated aging, or contributes to their reduced lifespan.     

Suppressions of Ischemic Paw Oedema in Mice, Rats and Guinea Pigs by Superoxide Dismutases from Different Sources

Various sources of superoxide dismutases (SOD) suppressed ischaemic paw oedemata (tourniquet poditis) of mice, rats and guinea pigs with different potencies. Intravenous (i.v.) dosing of mouse Cu, Zn-SOD had no effect on mouse ischaemic oedema, yet rat and guinea pig Cu, Zn-SOD suppressed ischaemic oedemata of rats and guinea pigs. Homologous SOD was anti-inflammatory at least in these two models. Guinea pig SOD was one of the most potent in all models, but showed a very narrow range of effective dose. This bell-shape suppressive pattern was ameliorated by concomitant catalase injection. Bovine and human Cu, Zn-SOD had a rather broad range of effective dose. Bacterial Mn-SODS were suppressive in mice, as well as the oxygen radical scavenger MK-447 and cytochrome c. Dexamethasone was effective only when administered more than 3 hrs in advance. As ischaemic paw oedema of mice was not sensitive to cyclooxy-genase and lipoxygenase inhibitors, this model could serve for screening new types of anti-inflammatory or anti-ischaemic drugs.     

Suppressions of Ischemic Paw Oedema in Mice,Rats and Guinea Pigs by Superoxide Dismutases from Different Sources

Various sources of superoxide dismutases (SOD) suppressed ischaemic paw oedemata (tourniquet poditis) of mice, rats and guinea pigs with different potencies. Intravenous (i.v.) dosing of mouse Cu, Zn-SOD had no effect on mouse ischaemic oedema, yet rat and guinea pig Cu, Zn-SOD suppressed ischaemic oedemata of rats and guinea pigs. Homologous SOD was anti-inflammatory at least in these two models. Guinea pig SOD was one of the most potent in all models, but showed a very narrow range of effective dose. This bell-shape suppressive pattern was ameliorated by concomitant catalase injection. Bovine and human Cu, Zn-SOD had a rather broad range of effective dose. Bacterial Mn-SODS were suppressive in mice, as well as the oxygen radical scavenger MK-447 and cytochrome c. Dexamethasone was effective only when administered more than 3 hrs in advance. As ischaemic paw oedema of mice was not sensitive to cyclooxy-genase and lipoxygenase inhibitors, this model could serve for screening new types of anti-inflammatory or anti-ischaemic drugs.     

Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels

Reactive oxygen species (ROS) have been proposed to mediate vasodilation in the microcirculation. We investigated the role of ROS in arachidonic acid (AA)-induced coronary microvascular dilation. Porcine epicardial coronary arterioles (110 +/- 4 microm diameter) were mounted onto pipettes in oxygenated Krebs buffer. Vessels were incubated with vehicle or 1 mM Tiron (a nonselective ROS scavenger), 250 U/ml polyethylene-glycolated (PEG)-superoxide dismutase (SOD; an O2- scavenger), 250 U/ml PEG-catalase (a H2O2 scavenger), or the cyclooxygenase (COX) inhibitors indomethacin (10 microM) or diclofenac (10 microM) for 30 min. After endothelin constriction (30-60% of resting diameter), cumulative concentrations of AA (10(-10)-10(-5)M) were added and internal diameters measured by video microscopy. AA (10-7 M) produced 37 +/- 6% dilation, which was eliminated by the administration of indomethacin (4 +/- 7%, P < 0.05) or diclofenac (-8 +/- 8%, P < 0.05), as well as by Tiron (-4 +/- 5%, P < 0.05), PEG-SOD (-10 +/- 6%, P < 0.05), or PEG-catalase (1 +/- 4%, P < 0.05). Incubation of small coronary arteries with [3H]AA resulted in the formation of prostaglandins, which was blocked by indomethacin. In separate studies in microvessels, AA induced concentration-dependent increases in fluorescence of the oxidant-sensitive probe dichlorodihydrofluorescein diacetate, which was inhibited by pretreatment with indomethacin or by SOD + catalase. We conclude that in porcine coronary microvessels, COX-derived ROS contribute to AA-induced vasodilation.     

Restoration of antioxidants in liver by methionine feeding in experimental rat urolithiasis.

The effect of methionine or citrate on antioxidant defense system has been studied in urolithic rat. Liver weight and its protein concentration did not change in the rats fed with calculi producing diet (CPD) when compared to normal diet fed rats. Feeding rats along with citrate (c-CPD) or methionine (m-CPD) improved their body weight gain. Liver microsomes and mitochondria fractions of CPD and c-CPD fed groups showed increased susceptibility for lipid peroxidation in presence of ascorbate and t-butyl hydroperoxide when compared to either control or m-CPD fed groups. Increased superoxide dismutase and xanthine oxidase activities, decreased catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities, decreased concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin-E and increased formation of hydroxyl radical, hydroperoxides and diene conjugates were observed in the liver of both CPD fed group as well as c-CPD fed group. Except SOD and xanthine oxidase, all other parameters were normalized in m-CPD fed group. This suggested that feeding methionine reduced the susceptibility for lipid peroxidation by restoration of the level of free radical scavengers.     

Modulation of restraint stress induced oxidative changes in rats by antioxidant vitamins

In the present study we examined immobilization stress-induced antioxidant defense changes in rat plasma and also observed the antioxidant effects of pre and post vitamins A, E and C administration (15 mg/Kg of body weight) individually and in combination (vit E + C) on these alterations.Following immobilization stress the circulating activities of superoxide dismutase, catalase and glutathione-S-transferase were decreased, while the level of thiobarbituric acid reactive substances (TBARS) was increased as compared to non-stressed control rats.Post treatment with individual vitamins A, E and C (after exposure to stress) resulted in a less marked alteration of plasma TBARS levels and activities of SOD, GST and catalase as compared to pre vitamin stress or stress alone treatments. Both pre and post vitamin treatments were effective in preventing stress induced derangement of free radical metabolism with a relative dominance by latter. The combined treatment with vitamin E and C did not show any additive antioxidant effect on restraint stress induced altered free radical metabolism, rather a predominant effect similar to vitamin E alone was observed. The prevention of oxidative stress generated in response to restraint stress by the vitamins can be summarized as: vitamin (E + C) i.e. vit E > vit C > vit A, thus combined vitamin (E + C) treatment though showed maximum preventive effect, but was similar to vitamin E treatment alone, in terms of the circulating activities of SOD, GST, catalase and TBARS levels.     

The Effects of Alpha-Tocopherol on Hippocampal Oxidative Stress Prior to in Pilocarpine-Induced Seizures

Reactive oxygen species have been implicated in seizure-induced neurodegeneration, and there is a correlation between free radical level and scavenger enzymatic activity in the epilepsy. It has been suggested that pilocarpine-induced seizures is mediated by an increase in oxidative stress. Current research has found that antioxidant may provide, in a certain degree, neuroprotection against the neurotoxicity of seizures at the cellular level. Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol (TP) in rats, against oxidative stress caused by pilocarpine-induced seizures. 30 min prior to behavioral observation, Wistar rats were treated with, 0.9% saline (i.p., control group), TP (200 mg/kg, i.p., TP group), pilocarpine (400 mg/kg, i.p., P400 group), or the combination of TP (200 mg/kg, i.p.) and pilocarpine (400 mg/kg, i.p.). After the treatments all groups were observed for 6 h. The enzymatic activities, lipid peroxidation and nitrite concentrations were measured using speccitrophotometric methods and these data were assayed. In P400 group mice there was a significant increase in lipid peroxidation and nitrite levels. However, no alteration was observed in superoxide dismutase (SOD) and catalase activities. In the TP and pilocarpine co-administered mice, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content, as well as increased the SOD and catalase activities in rat hippocampus after seizures. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus during pilocarpine-induced seizures, indicate that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and imply that strong protective effect could be achieved using alpha-tocopherol.     

Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary

The potential role of oxygen free radicals in hCG-induced ovulation was investigated using the free radical scavenging enzymes superoxide dismutase (SOD) and/or catalase with the in-vitro perfused rabbit ovary preparation. SOD (25 micrograms/ml) and SOD + catalase (25 micrograms/ml) significantly reduced the % of large follicles that ovulated during perfusion (P less than 0.005). Neither maturity nor degeneration of ovulated ova and follicular oocytes was affected by SOD and/or catalase. Progesterone concentration in the perfusate was significantly increased in the SOD + catalase treatment group (P less than 0.01). These results indicate a significant role for oxygen free radicals in the process of ovulation.     

Thyroxine induced stress and its possible prevention by catechin

Free radicals are all known to damage cell components. The present study was designed to evaluate the free radical generation in the testis and liver and also to determine the testicular and hepatic antioxidant enzyme activities with and without catechin administration in thyroxine induced male Sprague-Dawley rats. The experimental animals were divided into four groups, six on each division. L-thyroxine (T4) (0.3 mg/kg body weight) was administered to experimental groups for 15 days. Another group (CAT-T4) was administered with L-thyroxine (T4) in the dose as mentioned and catechin (100 mg/kg of body weight/day) simultaneously. Third group was administered only with catechin, and the remaining group was kept as control. Lipid peroxidation level (LPO) increased in L-thyroxine treated rats as compared to control, while LPO level was almost normal in L-thyroxine (T4) and catechin (CAT-T4) treated group. Superoxide dismutase (SOD) and catalase activities were increased in L-thyroxine (T4) treated rats as compared to control, where as there were almost at normal level in L-thyroxine (T4) and catechin (CAT-T4) treated groups. The results show that, thyroxine administration develops oxidative stress; the organism defends it against the effects of oxidative stress by increasing SOD and catalase activities as a protective mechanism and catechin, being an antioxidant, normalizes lipid peroxidation in testis and liver including SOD and catalase activities.     

Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas

The aim of this study was to analyze the effect of the flavonoid silymarin, a free radical scavenger that prevents lipoperoxidation, on the pancreatic activity of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) in rats with alloxan-induced diabetes mellitus. Alloxan intoxicated rats were treated with silymarin in two manners, simultaneously (four or eight doses) or 20 days after alloxan administration for 9 weeks. Alloxan elicited a transient increase in the activity of the three enzymes, which decreased after 5 days of treatment. On its own, silymarin significantly increased the activity of these enzymes. Simultaneous treatment with alloxan and silymarin also induced an increment in the activity of the enzymes followed by a delayed decrease (four doses). However, a longer treatment with silymarin (eight doses) induced a more sustained effect. Interestingly, silymarin treatment recovered to control values for the activity of the three-antioxidant enzymes that were significantly diminished after 20 days of alloxan administration. It is suggested that the protective effect of silymarin on pancreatic damage induced by alloxan may be due to an increase in the activity of antioxidant enzymes that, in addition to the glutathione system, constitute the more important defense mechanisms against damage by free radicals.     

Antidiabetic effect of Scoparia dulcis: effect on lipid peroxidation in streptozotocin diabetes

Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. The antioxidant effect of an aqueous extract of Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India was studied in rats with streptozotocin-induced diabetes. Oral administration of Scoparia dulcis plant extract (SPEt) (200 mg/kg body weight) for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin. The aqueous extract also resulted in decreased free radical formation in tissues (liver and kidney) studied. The decrease in thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HPX) and increase in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and glutathione-S-transferase (GST) clearly show the antioxidant properties of SPEt in addition to its antidiabetic effect. The effect of SPEt at 200 mg/kg body weight was better than glibenclamide, a reference drug.     

Free radicals alter maximal diaphragmatic mitochondrial oxygen consumption in endotoxin-induced sepsis

Recent studies indicate that sepsis is associated with enhanced generation of several free radical species (nitric oxide, superoxide, hydrogen peroxide) in skeletal muscle. While studies suggest that free radical generation causes uncoupling of oxidative phosphorylation in sepsis, no previous report has examined the role of free radicals in modulating skeletal muscle oxygen consumption during State 3 respiration or inhibiting the electron transport chain in sepsis. The purpose of the present study was to examine the effects of endotoxin-induced sepsis on State 3 diaphragm mitochondrial oxygen utilization and to determine if inhibitors/scavengers of various free radical species would protect against these effects. We also examined mitochondrial protein electrophoretic patterns to determine if observed endotoxin-related physiological derangements were accompanied by overt alterations in protein composition. Studies were performed on: (a) control animals, (b) endotoxin-treated animals, (c) animals given endotoxin plus PEG-SOD, a superoxide scavenger, (d) animals given endotoxin plus L-NAME, a nitric oxide synthase inhibitor, (e) animals given only PEG-SOD or L-NAME, (f) animals given endotoxin plus D-NAME, and (g) animals given endotoxin plus denatured PEG-SOD. We found: (a) no alteration in maximal State 3 mitochondrial oxygen consumption rate at 24 h after endotoxin administration, but (b) a significant reduction in oxygen consumption rate at 48 h after endotoxin, (c) no effect of endotoxin to induce uncoupling of oxidative phosphorylation, (d) either PEG-SOD or L-NAME (but neither denatured PEG-SOD nor D-NAME) prevented endotoxin-mediated reductions in State 3 respiration rates, (e) some mitochondrial proteins underwent tyrosine nitrosylation at 24 h after endotoxin administration, and (f) SDS-page electrophoresis of mitochondria from endotoxin-treated animals revealed a selective depletion of several proteins at 48 h after endotoxin administration (but not at 24 h); (g) administration of L-NAME or PEG-SOD prevented this protein depletion. These data provide the first evidence that endotoxin-induced reductions in State 3 mitochondrial oxygen consumption are free radical-mediated.     

Early macrophage infiltration in mice treated with low-dose streptozocin decreases islet superoxide dismutase levels: prevention by silica pretreatment.

It has been hypothesized that streptozocin (STZ) given in low doses for 5 consecutive days produces diabetes by induction of peroxidation phenomena similar to those induced by free radicals. Moreover, it has been demonstrated that macrophages are among the first to invade the pancreatic parenchyma and destroy islet B cells supposedly by the release of interleukin-1 that induces free radical formation. Superoxide dismutase (SOD) is a free radical scavenger present in cells, and islet B cells are known to have extremely low levels of this enzyme. Therefore, our aim was to observe SOD activity concomitantly with the appearance of intra-islet macrophages, in early diabetes induced by low-dose streptozocin (LDS). Silica-pretreated mice showed SOD values which were comparable to those found in control animals. In LDS-only-treated mice we found that SOD levels were decreased even after only 4 days from the last STZ injection and that it is at this time that the first 'recruited' macrophages appear in the islets. Moreover, the SOD levels found at this early stage (animals were still normoglycaemic and therefore not as yet diabetic) were similar to levels found by us in a previous work, in prediabetic Bio Breeding rats, thereby ascribing a crucial factor to the lowering of SOD levels even in LDS-induced diabetes.     

Prevention of oxygen toxicity with superoxide dismutase and catalase in premature lambs

The use of high oxygen concentrations and high mean airway pressures during mechanical ventilation of premature newborn infants with respiratory distress syndrome leads in 20%–30% of the survivors to chronic lung disease. This study explores if exogenous polyethylene glycol conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) mitigate oxygen toxicity in premature lambs with respiratory distress syndrome. Six pairs of premature lambs were delivered by cesarean section and treated by tracheal instillation of 60 mg natural sheep surfactant/kg/body weight. After birth, all lambs were ventilated with 100% oxygen, and one of each pair received a single intravenous injection of 1 million U/kg PEG-CAT and 50,000 U/kg PEG-SOD. At 8 h of age or after respiratory failure was established, the lambs were killed and the lungs were removed intact. Lung damage was assessed by microscopy. The arterial blood gases, pH, and mean airway pressures of the lambs treated with PEG-SOD/PEG-CAT did not differ from those of the controls. Mean PaO₂ was > 140 mmHg during the first 4 h of the experiments. In the lambs treated with PEG-SOD/PEG-CAT, SOD and CAT levels were very high during the study period and less bronchiolar epithelial damage and lung hemorrhages were found at microscopy.     

The ability of (-)deprenyl to increase superoxide dismutase activities in the rat is tissue and brain region selective.

In a previous study we have shown that chronic administration of (-)deprenyl increases activities of superoxide dismutase (SOD) and catalase (CAT) in rat striatum (1). The present study attempted to clarify how specific the effect of deprenyl is to certain tissues and brain regions in the rat. Two mg/kg/day of deprenyl was continuously infused s.c. in young male Fischer-344 rats. On the 22nd day, rats were sacrificed and enzyme activities of SOD and CAT were determined in several different brain regions and the liver. Activities of both SOD and CAT were significantly increased in striatum and substantia nigra but not in hippocampus, cerebellum or liver. Both types of SOD (i.e. Cu Zn-SOD and Mn-SOD) were significantly increased in striatum, substantia nigra. Interestingly, in cerebral cortices of three different regions, activities also tended to increase (especially those of Mn-SOD), although the increase was not so striking as in substantia nigra and striatum. The results confirm the previous observation that (-)deprenyl can increase free radical scavenger enzyme activities in striatum and provide further evidence that this effect is selective to certain brain regions and tissue types.