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1.
Rasagiline [N-propargyl-l(R)-aminoindan] is a selective irreversible MAO-B inhibitor as is (-)deprenyl. The effect of the drug on antioxidant enzyme activities on dopaminergic tissue was examined in male F-344 rats (8.5-months-old). Two experimental groups were infused subcutaneously with rasagiline saline solutions by means of osmotic minipumps implanted subcutaneously in the back of the rats. Control animals were also similarly implanted with saline filled mini-pumps. Three-and-one-half weeks later, animals were sacrificed and selected tissue samples removed from brain, kidney and heart. Two doses of rasagiline (0.5 mg/kg/day, 1.0 mg/kg/day, both for 3.5 weeks) significantly increased catalase activities about 2-fold in substantia nigra and striatum but not in hippocampus. Interestingly, in both renal cortex and medulla. catalase (CAT) activities were significantly increased. Both Mn- and Cu,Zn-superoxide dismutase (SOD) activities were increased 2 to 4 fold in substantia nigra, striatum and renal cortex and heart. Several groups, including our own have reported an extension of survival of deprenyl-treated animals of different species. Although the mechanism(s) of the life extension by deprenyl remains unresolved, it would be interesting to investigate the effect of rasagiline on the survival of animals, since deprenyl also was shown to increase antioxidant enzyme activities in brain dopaminergic regions.  相似文献   

2.
M C Carrillo  K Kitani  S Kanai  Y Sato  G O Ivy 《Life sciences》1992,50(25):1985-1992
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.  相似文献   

3.
Six-month old male rats were treated with 0.25 mg/kg, s.c., (-)p-fluoro-deprenyl (n = 40) or salt solution (n = 20) three times a week for 25 months. Three of the 20 saline-treated and 15 of the 40 drug-treated males survived (p = 0.05). Sexual activity of the survivors was tested at the end of the experiment. Three of the (-)p-fluoro-deprenyl-treated 31-month-old males proved to be sexually fully active, though, Wistar rats lose their ability to ejaculate by completing their second year of life. Non-copulator, 13 month old male rats were treated instead of the usually used 0.25 mg/kg dose with 0.01 mg/kg, s.c., (-)deprenyl (n = 9), (-)p-fluoro-deprenyl (n = 9) and salt solution (n = 9), three times a week, for 82 weeks and mating activity was tested weekly. The lifespan of the non-copulators was very short: 102 weeks for saline (n = 9), 106 weeks for (-)deprenyl (n = 8) and 104 weeks for (-)p-fluoro-deprenyl (n = 7). Survival was lightly changed by this very small dose treatment, one (-)deprenyl-treated male and two (-)p-fluoro-deprenyl-treated rats remained alive. The copulatory activity, however, was substantially improved.  相似文献   

4.
Aging is characterized by development of diseases and cancer due to loss of central and peripheral neuroendocrine-immune responses. Free radicals exert deleterious effects on neural-immune functions in the brain, heart, and lymphoid organs and thus, affecting the health. Bacopa monnieri (brahmi), an Ayurvedic herb, and l-deprenyl, a monoamine oxidase-B inhibitor, have been widely used in the treatment of neurodegenerative diseases. The purpose of this study was to investigate whether brahmi (10 and 40 mg/kg BW) and deprenyl (1 and 2.5 mg/kg BW) treatment of 3-month old female Wistar rats for 10 days can modulate the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)] in the brain and spleen. In addition, the effects of these compounds on the expression of tyrosine hydroxylase (TH), nerve growth factor (NGF), the intracellular signaling markers, p-ERK1/2, p-CREB, and p-NF-kB, and nitric oxide (NO) production were measured in the spleen by Western blot analysis. Both brahmi and deprenyl enhanced CAT activity, and p-TH, NGF, and p-NF-kB expression in the spleen. However, deprenyl alone was found to enhance the p-ERK1/2 and p-CREB expression in the spleen. The activities of SOD, CAT, and GPx in the thymus, mesenteric lymph nodes, heart, and brain areas (frontal cortex, medial basal hypothalamus, striatum, and hippocampus) were differentially altered by brahmi and deprenyl. Brahmi alone enhanced NO production in the spleen. Taken together, these results suggest that both brahmi and deprenyl can protect the central and peripheral neuronal systems through their unique effects on the antioxidant enzyme activities and intracellular signaling pathways.  相似文献   

5.
Brain antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels were studied in the brains of early diabetic (72 hr) and long term diabetic (one month) rats. Diabetes was induced by injecting streptozotocin (50 mg/kg, i.p.) in citrate buffer. One group of diabetic rats was treated with insulin (1U/day/animal). The results indicate that early diabetic rats exhibit increased SOD and CAT activities with no alteration in the GPX activity. On the contrary, increased CAT decreased GPX activities with no alteration in the SOD activity, was noted in the long-term Diabetic rats. Insulin treatment reversed these alterations in both the groups. It can be concluded that, in diabetic condition antioxidant enzyme levels are elevated and insulin treatment attenuated these changes. Hence, diabetes mellitus, if left untreated, may initiate degenerative processes and other CNS complications due to accumulation of oxidative free radicals.  相似文献   

6.
Studies have demonstrated that oxidative stress is associated with amphetamine-induced neurotoxicity, but little is known about the adaptations of antioxidant enzymes in the brain after amphetamine exposure. We studied the effects of acute and chronic amphetamine administration on superoxide dismutase (SOD) and catalase (CAT) activity, in a rodent model of mania. Male Wistar rats received either a single IP injection of d-amphetamine (1 mg/kg, 2 mg/kg, or 4 mg/kg) or vehicle (acute treatment). In the chronic treatment rats received a daily IP injection of either d-amphetamine (1 mg/kg, 2 mg/kg, or 4 mg/kg) or vehicle for 7 days. Locomotor behavior was assessed using the open field test. SOD and CAT activities were measured in the prefrontal cortex, hippocampus, and striatum. Acute and to a greater extent chronic amphetamine treatment increased locomotor behavior and affected SOD and CAT activities in the prefrontal cortex, hippocampus and striatum. Our findings suggest that amphetamine exposure is associated with an imbalance between SOD and CAT activity in the prefrontal cortex, hippocampus and striatum.  相似文献   

7.
The aim of this study was to investigate the long-lasting effects of prolonged administration of ethanol doses on oxidative processes of aged rats. We determined the activity of superox-ide dismutase (SOD), catalase (CAT), and gluta-thione peroxidase (GPx) in erythrocytes of rats 15, 20, and 24 months old treated with an average daily dose of 1.5 g/Kg of ethanol or saline administered intraperitoneally for 13 weeks and after a 2 month period of withdrawal from treatment. The activity of all three enzymes decreased significantly with aging in the controls, while no age-related changes were found among treated rats. These findings are important since they are the first to show a long-lasting toxic effect of low ethanol doses observed in association with the aging process.  相似文献   

8.
In this study, the antiulcerogenic effect of a water extract obtained from the lichen species Usnea longissima was investigated using indomethacin-induced ulcer models in rats. Experimental groups consisted of six rats. Antiulcerogenic activities of 50, 100 and 200mg/kg body wt. doses of the water extract were determined by comparing the negative (treated only with indomethacin) and positive (ranitidine) control groups. Although all doses of the water extract of U. longissima showed significant antiulcerogenic activity as compared to negative control groups, the highest activity was observed with 100 mg/kg body wt. doses (79.8%). The water extract of U. longissima showed moderate antioxidant activity when compared with trolox and ascorbic acids used as positive antioxidants. In addition, the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)] were determined in the stomach tissues of rats and compared with those of the negative and positive control groups to expose the effects of antioxidant enzymes on antiulcerogenic activity. SOD and GST enzymes activities in indomethacin-administrated tissues were reduced significantly by indomethacin in comparison to control groups. These enzymes were activated, however, by the water extracts of U. longissima. In contrast to SOD and GST activities, CAT activity was increased by indomethacin and reduced by all doses of U. longissima and ranitidine. The present results indicate that the water extract of U. longissima has a protective effect in indomethacin-induced ulcers, which can be attributed to its antioxidant potential.  相似文献   

9.
The antioxidant activity of tannoid active principles of E. officinalis consisting of emblicanin A (37%), emblicanin B (33%), punigluconin (12%) and pedunculagin (14%), was investigated on the basis of their effects on rat brain frontal cortical and striatal concentrations of the oxidative free radical scavenging enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and lipid peroxidation, in terms of thiobarbituric acid-reactive products. The results were compared with effects induced by deprenyl, a selective monoamine oxidase (MAO) B inhibitor with well documented antioxidant activity. The active tannoids of E. officinalis (EOT), administered in the doses of 5 and 10 mg/kg, i.p., and deprenyl (2 mg/kg, i.p.), induced an increase in both frontal cortical and striatal SOD, CAT and GPX activity, with concomitant decrease in lipid peroxidation in these brain areas when administered once daily for 7 days. Acute single administration of EOT and deprenyl had insignificant effects. The results also indicate that the antioxidant activity of E. officinalis may reside in the tannoids of the fruits of the plant, which have vitamin C-like properties, rather than vitamin C itself.  相似文献   

10.
Daily s.c. injection of (-)deprenyl (2.0 mg/kg/day) for three weeks in young male rats caused a threefold increase in superoxide dismutase (SOD) activity in the striatum of the brain compared with the value in saline-injected control rats. Furthermore, the activity of catalase (but not of glutathione peroxidase) was also increased significantly by deprenyl treatment. The results confirmed the previous findings of Knoll on SOD activity and furthermore provided evidence that the activity of catalase is also significantly induced by the drug, which was not found in the previous study.  相似文献   

11.
目的:研究阿里红黄酮对衰老模型小鼠的抗衰老作用。方法:将小鼠随机分为6组(n=12):正常对照组,衰老模型组,阳性对照组,低、中、高剂量阿里红黄酮组。除正常对照组外,其余各组均采用D-半乳糖颈背部皮下注射建立亚急性衰老小鼠模型,用不同剂量的阿里红黄酮(100、200和400 mg/(kg·d))灌服小鼠6周后,计算衰老模型小鼠脑指数及脾脏指数、胸腺指数,测定其脑组织丙二醛(MDA)含量及谷胱甘肽过氧化物酶(GSH-Px)活性、肝组织过氧化氢酶(CAT)及超氧化物歧化酶(SOD)活性。结果:阿里红黄酮3个剂量组可不同程度的升高衰老模型小鼠的脑指数、脾脏指数、胸腺指数、脑组织中的GSH-Px活性及肝组织中的CAT、SOD活性,降低其脑组织中的MDA含量。结论:阿里红黄酮可能通过提高机体的抗氧化能力而达到抗衰老作用。  相似文献   

12.
The effects of Echis pyramidum venom (EPV) (0.25, 0.50, and 1.00 mg/kg) on activities of superoxide dismutase (SOD) and catalase (CAT) and levels of thiobarbituric acid reactive substances (TBARS) and total thiols (T‐SH) in liver and kidneys of rats were investigated. EPV significantly and dose dependently decreased the activities of SOD and CAT in livers. Although the kidney SOD and CAT activities were not affected by low and medium doses of EPV, the high dose significantly reduced the activities of these enzymes. Liver and kidney TBARS levels were not affected by the low and medium doses of EPV, whereas the high dose significantly increased the TBARS after 6 h postdosing. There was a significant depletion of T‐SH in liver and kidneys of rats exposed to a high dose of EPV. The acute phase oxidative stress due to an EPV injection points toward the importance of an early antioxidant therapy for the management of snake bites.  相似文献   

13.
An imbalance between production of reactive oxygen species (ROS) and its elimination by antioxidant defense system in the body has been implicated for causes of aging and neurodegenerative diseases. This study was design to assess the changes in activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase), lipid peroxidation and reduced glutathione (GSH) levels in the brain of 2, 10 and 20 month old rats, and to determine the effect of safranal on the status of selected oxidative stress indices in the 10 and 20 month old rats. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results of this study demonstrated that aging caused significant increase in the level of lipid peroxidation as well decrease in the GSH level and activities of SOD and GST in the brain of aging rats. The results of this study showed that safranal ameliorated the increased lipid peroxidation level as well as decreased GSH content of the brain of 10 and 20 month old rats. In addition, safranal treatment to the 20 month old rats, which restored the SOD and GST activities. In conclusion, safranal can be effective to protect susceptible aged brain from oxidative damage by increasing antioxidant defenses.  相似文献   

14.
Antioxidants are free radical scavengers and protect living organisms against oxidative damage to tissues. Experimental evidence implicates oxygen-derived free radicals as important causative agents of aging and the present study was designed to evaluate the age-related effects of deprenyl on the antioxidant defense in the cerebellum of male Wistar rats. Experimental rats of three age groups (6, 12, and 18 months old) were administered with liquid deprenyl (2 mg/kg body weight/day for a period of 15 days i.p) and levels of diagnostic marker enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase) in plasma, lipid peroxides, reduced glutathione and activities of glutathione-dependent antioxidant enzymes (glutathione peroxidase and glutathione-S-transferase) and antiperoxidative enzymes (catalase and superoxide dismutase) in the cerebellar tissue were determined. Intraperitonial administration of deprenyl (2 mg/kg body weight/day for a period of 15 days) significantly (p < 0.05) attenuated the age-related alterations noted in the levels of diagnostic marker enzymes plasma of experimental animals. Deprenyl also exerted an antioxidant effect against aging process by hindering lipid peroxidation to an extent. Moderate rise in the levels of reduced glutathione and activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. The results of the present investigation indicated that the protective potential of deprenyl was probably due to the increase of the activity of the free radical scavenging enzymes or to a counteraction of free radicals by its antioxidant nature or to a strengthening of neuronal membrane by its membrane-stabilizing action. Histopathological observations also confirmed the protective effect of deprenyl against the age-related aberrations in rat cerebellum. These data on the effect of deprenyl on parameters of normal aging provides new additional information concerning the anti-aging potential of deprenyl.  相似文献   

15.
The effect of various doses (0, 10, 20, 40, or 80 mg/kg body weight) of naringin (a citrus flavonone) was studied on streptozotocin (STZ)-induced hyperglycaemic rats to evaluate the possible hypoglycaemic and antioxidant activity of naringin in diabetes. In comparison to the normoglycaemic group the treatment of rats with a single dose of STZ (65 mg/kg body weight) only revealed a significant increase (P < 0.05) in plasma hydrogen peroxide (H2O2) by 230%, increased the thiobarbituric acid reactive substances (TBARS) as index of the lipid peroxidation level by 69%, while total antioxidant activity was decreased by 36%, with a consistent significant decrease (P < 0.05) in the activity of erythrocytes antioxidative enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase (PON). Exogenous administration of individual gradual doses of naringin to hyperglycaemic rats causes a dose-dependent decrease of the glucose level, an increase of the insulin concentration, a decrease of the H2O2 and TBARS levels, as well as the increase of the total antioxidant status with an increase of antioxidant enzyme activities (CAT, SOD, GPx, and PON). From this study, it may be concluded that all doses of naringin provided a significant amelioration of hypoglycaemic and antioxidant activity in STZ-induced diabetic rats, however, the greatest effect of naringin was observed at 80 mg/kg body weight.  相似文献   

16.
Erythrocytes from young (6–8 month old) and old (28–31 month old) WF rats were separated into four age fractions by centrifugation on a discontinuous, isotonic, arabinogalactan density gradient. Specific activities of super-oxide dismutase (SOD) with respect to activity per unit hemoglobin (Hb) and activity per cell were determined for each cell age group. SOD activity was found to diminish with respect to erythrocyte age. More significantly, it was found that young erythrocytes of old animals already contain considerably reduced SOD activity as compared to cells of young animals. The level of SOD catalytic activity per unit enzyme antigen was also found to decrease with both increasing cell and animal age. Young cells of old animals contain significant amounts of catalytically altered molecules.  相似文献   

17.
Wistar albino rats (150-200 g) were fed raw garlic homogenate orally in three different doses (125, 250, 500 mg/kg/day) for 30 days. Isoproterenol (85 mg/kg, s.c. 2 doses at 24-h interval, animals sacrificed after 24 h of last injection) induced myocardial necrosis in control rats and after 30 days of garlic feeding. Myocardial oxidative stress was evident following isoproterenol administration by reduction in myocardial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities along with a rise in plasma thiobarbituric acid reactive substances (TBARS). Myocardial necrosis was evident from the light microscopic and ultrastructural changes, along with a rise in plasma lactate dehydrogenase (LDH). Significant preservation of myocardial SOD activity was observed in all the garlic-fed rats. However, there was no significant change in myocardial reduced glutathione level and GPx activity in any of the treated groups. Significant reduction in plasma TBARS and LDH levels was observed in the 500 mg/kg garlic treated group. Isoproterenol-induced myocardial morphological changes were least in the 250 and 500 mg/kg garlic treated groups. The results suggest that chronic oral administration of raw garlic offered protection against isoproterenol-induced myocardial necrosis and associated oxidative stress.  相似文献   

18.
It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. The protective effect of binaphthyl diselenide (NapSe)2 was investigated in ethanol (Etoh)-induced brain injury. Thirty male adult Wistar rats were divided randomly into five groups of six animals each and treated as follows: (1) The control group received the vehicle (soy bean oil, 1 mL/kg, p.o.). (2) Ethanol group of animals was administered with ethanol (70% v/v, 2 mL/kg, p.o.). (3) (NapSe)2 1 mg/kg, 1 mL/kg plus ethanol 70% (v/v, 2 mL/kg, p.o. (5) (NapSe)2 10 mg/kg, 1 mL/kg) plus ethanol 70% (v/v, 2 mL/kg, p.o). After acute treatment, all rats were sacrificed by decapitation. Evidence for oxidative stress in rat brain was obtained from the observed levels of thiobarbituric acid reactive species, of non-protein thiol (NPSH) groups, and of ascorbic acid, as well as from the activities of catalase (CAT) and of superoxide dismutase (SOD). (NapSe)2 compensated the deficits in the antioxidant defense mechanisms (CAT, SOD, NPSH, and ascorbic acid), and suppressed lipid peroxidation in rat brain resulting from Etoh administration. It was concluded that ethanol exposure causes alterations in the antioxidant defense system and induces oxidative stress in rat brain. (NaPSe)2 at 5 mg/kg restored the antioxidant defenses in rat brain and mitigated the toxic effects of alcohol, suggesting that could be used as a potential therapeutic agent for alcohol-induced oxidative damage in rat brain.  相似文献   

19.
Clinical studies have shown that anxiolytic and antidepressant drug therapy benefits patients with ulcers. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. This study investigated the antiulcer activities of tianeptine, trazodone, and venlafaxine on indomethacin-induced ulcers in rats; and evaluated tianeptine's effects on oxidant and antioxidant parameters in rat stomach tissue. The results show that trazodone and venlafaxine did not prevent indomethacin-induced ulcers. Tianeptine, however, decreased indomethacin-induced ulcers significantly at all doses used (6, 12, and 25 mg/kg). Famotidine, an H2 receptor blocker, showed the highest antiulcer activity. Tianeptine significantly prevented the decrease in glutathione (GSH) content that occurred in the indomethacin-only group's damaged stomach tissues. All doses of tianeptine, but especially the 25 mg/kg dose, significantly decreased catalase (CAT) activity in stomach tissue, compared to the control. All doses of tianeptine eliminated the decrease in superoxide dismutase (SOD) activity in the stomach tissue of rats given indomethacin. Although all doses of tianeptine significantly decreased the malondialdehyde (MDA) content, all doses of tianeptine, except 6 mg/kg, decreased myeloperoxidase (MPO) activities significantly compared to the control. Our results indicate that activating enzymatic and non-enzymatic antioxidant mechanisms and inhibiting some toxic oxidant mechanisms play a role in tianeptine's antiulcer effect mechanism.  相似文献   

20.
The aim of this study was to assess the effects of subchronic exposure to cadmium (Cd) on the antioxidant defense system of red blood cells (RBCs) and lipid peroxide concentration in the plasma, as well as the possible protective role of zinc (Zn). For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl2, administered in five doses (each of 0.4 mg Cd/kg BW) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg BW, i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl2, administered in doses of 0.8 mg Zn/kg BW, giving a total dose of 4 mg Zn/kg BW, i.p.; a control group received 0.5 mL of physiological saline in an identical manner.

It was shown that exposure to Cd induced a significant decrease (p<0.05) in superoxide dismutase (Zn/Cu SOD) and catalase (CAT) activities in RBCs. Increased lipid peroxide concentration, measured by thiobarbituric acid reactive substances (TBARS), was also observed in the plasma of cadmium-exposed rats. Cd had no effect on glutathione peroxidase (GSH-Px) activity. Zn administration had a beneficial effect on the Cd-induced decrease in Zn/Cu SOD activity (p<0.05) but not on CAT activity. Animals receiving Cd and Zn simultaneously had significantly (p<0.05) lower concentrations of lipid peroxides than rats exposed to Cd alone. Our results indicate that Cd causes oxidative stress and that Zn supply in conditions of exposure to Cd can partially protect against Cd-induced oxidative stress.  相似文献   


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