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1.
Treatment with catalase and SOD (superoxide dismutase) could diminish the damage due to oxygen free radical formation, but these enzymes are rapidly removed from circulation. The covalent attachment of monomethoxypolyethylene glycol (PEG) to catalase and SOD extended their plasma half-lives. Toxicity of PEG-catalase and PEG-SOD was evaluated in mice and rats prior to their use as free radical scavengers. Rodents used in acute, subacute, and subchronic toxicologic studies could tolerate large doses of PEG-catalase and PEG-SOD without developing toxic signs. The conjugates did not affect survival rate, appearance, behavior, food intake, blood chemistry, hematology, or urinalysis. In general, body weight gains, organ weights, and histomorphology were also unaffected. Massive doses of PEG-catalase caused slight weight loss, splenic hypertrophy, and generalized splenic stimulation in mice. Massive doses of PEG-SOD resulted in vacuolation in splenic macrophages in rats. PEG-catalase and PEG-SOD circulated for 3 days and 8 days, respectively, in mice following i.v. or i.m. administration.  相似文献   

2.
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.  相似文献   

3.
In previous experimental studies in rabbits, we have shown that vasodilating drugs (including nifedipine) cause distal digital defects. These defects were preceded by edema, hemorrhage, and finally necrosis of the developed cartilage in the phalanges. The underlying mechanism is most likely a fetal hypoxic response, secondary to maternal hypotension and decreased uteroplacental blood flow. Since phenytoin is known to cause distal digital defects both in man and rabbits, we decided to compare the defects provoked by oral administration of phenytoin (100 mg/kg) versus nifedipine (8.3 mg/kg) to New Zealand White rabbits on days 6-18 of gestation. In order to investigate phase-specificity, phenytoin (150 mg/kg) was given on days 14-17. The result of single dose administration on day 16 of phenytoin (300 mg/kg) versus nifedipine (33.2 mg/kg) was also studied. In this latter experiment maternal heart rate was measured up to 21 hours after phenytoin administration. Phenytoin induced digital defects identical with those produced by nifedipine and caused marked maternal cardiodepression. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanges. The distal phalanx of the fourth digit on the hindpaw was the first to be affected, with inclusion of other phalanges, both on the hind- and forepaws, with increasing dose. The sensitive period for induction and histological appearance of these defects was identical for phenytoin and nifedipine. These results suggest that vascular disruption due to a fetal hypoxic response lies behind phenytoin teratogenicity, as has been shown for vasodilators. A cardiodepressive action on the maternal and fetal hearts, possibly in combination with decreased uteroplacental blood flow, is discussed as a probable factor behind phenytoin teratogenicity.  相似文献   

4.
Selenium (Se) is a multifunctional trace element required in specific amounts for the optimal growth of aquatic finfish species. For this reason, this study investigated the effect of Se nanoparticles on the growth behavior, antioxidative capacity, and liver wellbeing of Striped catfish (Pangasianodon hypophthalmus). Striped catfish fed varying Se nanoparticles levels (0. 0.5, 1, and 2 mg/kg) in triplicate units and kept for 60 days. Striped catfish delivered dietary Se nanoparticles had markedly increased growth performance, specific growth rate (SGR), consumed feed, and protein efficiency ratio but reduced feed conversion ratio (FCR). The whole body, liver, muscle, and gills have higher Se accumulation levels in fish that received Se nanoparticles than the control with the highest level in fish fed 2 mg/kg. The carcass composition showed higher protein content in fish fed 1 and 2 mg/kg (p = 0.001 and 0.001) and higher ash content (p = 0.001 and 0.002) in fish fed 2 mg/kg than the remaining groups. Superoxide dismutase was meaningfully activated in Striped catfish delivered 1 and 2 mg Se nanoparticles/kg compared with the control (p < 0.05). Also, catalase and glutathione peroxidase activities were higher, and malondialdehyde level was lower in Striped catfish fed Se nanoparticles at 0.5, 1, and 2 mg/kg than the control (p < 0.05). The villi exhibited a visible increase in both height and branching with an increased level of Se nanoparticles in addition to the increased number of goblet cells. The Se nanoparticles-treated fish revealed dose-dependent modifications fluctuated from diffuse fatty vacuolization in hepatocytes with eccentric pyknotic hepatocytes nuclei. In conclusion, Se nanoparticles are required for the optimum growth behavior, antioxidative capacity, and liver wellbeing of Striped catfish. Based on SGR and FCR data's regression analysis, Se nanoparticles are recommended at 1.02–1.11 mg/kg diet.  相似文献   

5.
Pretreatment with diazoxide, KATP channel opener, increases tissue tolerance against ischemia reperfusion (IR) injury. In clinical settings pretreatment is rarely an option therefore we evaluated the effect of post-ischemic treatment with diazoxide on skeletal muscle IR injury. Rats were treated with either saline, diazoxide (KATP opener; 40?mg/kg) or 5-hydroxydecanoate (5-HD; mitochondrial KATP inhibitor; 40?mg/kg) after skeletal muscle ischemia (3?h) and reperfusion (6, 24 or 48?h). Tissue contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl-2 protein expression and muscle histology were determined. Apoptosis was examined (24 and 48?h) after ischemia. IR induced severe histological damage, increased MDA content and Bax expression (24 and 48?h; p?<?0.01) and decreased CAT and SOD activities (6 and 24?h, p?<?0.01 and 48?h, p?<?0.05), with no significant effect on Bcl-2 expression. Diazoxide reversed IR effects on MDA (6 and 24?h; p?<?0.05), SOD (6 and 24?h; p?<?0.01) and CAT (6 and 48?h, p?<?0.05 and 24?h p?<?0.01) and tissue damage. Diazoxide also decreased Bax (24 and 48?h; p?<?0.05) and increased Bcl-2 protein expression (24 and 48?h; p?<?0.01). Post-ischemic treatment with 5-HD had no significant effect on IR injury. Number of apoptotic nuclei in IR and 5-HD treated groups significantly increased (p?<?0.001) while diazoxide decreased apoptosis (p?<?0.01). The results suggested that post-ischemic treatment with diazoxide decrease oxidative stress in acute phase which modulates expression of apoptotic proteins in the late phase of reperfusion injury. Involvement of KATP channels in this effect require further evaluations.  相似文献   

6.
A murine embryo culture model was developed to study the potential contribution of enzymatic bioactivation to the teratogenicity of phenytoin. To assess the relative embryonic and maternal contributions to bioactivation, embryos were cultured respectively alone or in the presence of an exogenous source of cytochromes P-450 (P-450), which are thought to bioactivate phenytoin to a teratogenic reactive intermediate. Embryological development from gestational day 9 to day 10 was assessed, and bioactivation was quantified by the irreversible binding of radiolabeled phenytoin to embryonic protein. Embryos cultured with phenytoin and an exogenous P-450 bioactivating system showed a significant decrease in the incidence of turning and closure of the anterior neuropore, yolk sac diameter, and protein content as well as growth retardation. In the absence of an exogenous P-450 system, phenytoin did not decrease the incidence of turning or anterior neuropore closure but did cause growth retardation and a lesser but significant reduction in yolk sac diameter and embryonic protein content. An exogenous P-450 system enhanced the bioactivation of phenytoin, although significant activity also was detectable in embryos cultured without an exogenous bioactivating system. These results suggest that the embryo itself can enzymatically bioactivate embryotoxically significant amounts of phenytoin, and that bioactivation and embryotoxicity can be further enhanced, qualitatively and quantitatively, by an exogenous P-450 system, implicating a possible maternal contribution to phenytoin teratogenicity.  相似文献   

7.
Oxidative stress is revealed as the main contributor in the pathophysiology of neuroinflammation. Analyzing plasma and cerebrospinal fluid (CSF) of patients with different clinical phenotypes of neuroinflammation, defined as clinically isolated syndrome (CIS), and those defined as relapsing remitting multiples sclerosis (RRMS), we tested peripheral and CNS oxidative stress intensity in these neuroinflammatory acute attacks. All obtained values changes were assessed regarding clinical and radiological features of CNS inflammation. The obtained results revealed an increase in malondialdehyde levels in plasma and CSF in CIS and RRMS patients compared to control values (p < 0.05). The obtained values were most prevailed in both study group, CIS and RRMS, in patients with severe clinical presentation (p < 0.05). Measured activities of catalase and total superoxide dismutase were higher in CIS and RRMS patients in plasma compared to control values (p < 0.05), parallel with an increased catalase activity and decrease in superoxide dismutase activity in CSF regarding values obtained in control group (p < 0.05). The positive correlations regarding clinical score were obtained for all tested biomarkers (p < 0.01). Although the positive correlations were observed in MDA levels in plasma and CSF, for both study patients, and their radiological findings (p < 0.01), and a negative correlation in plasma SOD activity and CIS patients’ radiological findings (p < 0.01), no other similar correlations were obtained. These findings might be useful in providing the earliest antioxidative treatment in neuroinflammation aimed to preserve total and CNS antioxidative capacity parallel with delaying irreversible, later neurological disabilities.  相似文献   

8.
Alga-bacterium relationships between a Bacillus cereus strain L7 and Anabaena flos-aquae were studied based on the effects of the algicidal substances on algal growth indicators such as enzyme activity and membrane lipid peroxidation. When exposed to algae-lytic products at a concentration of 0.05?mg?mL?1, chlorophyll a (Chla), protein and phycobiliprotein contents increased significantly (p?<?0.05); superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and malondialdehyde (MDA) concentrations increased slightly to stimulate the algae growth. When exposed to algae-lytic products at a concentration of 0.5?mg?mL?1, algae growth and composition were inhibited. Chla, protein and phycobiliprotein concentrations decreased significantly (p?<?0.05 for protein, p?<?0.01 for Chla and phycobiliprotein). MDA concentrations increased significantly (p?<?0.05). POD and CAT activities increased by approximately six and three times, respectively, in 24?h compared with the control, then decreased to the initial level in 4?days. Algae-lytic products have not only inhibition but also stimulation effects on A. flos-aquae. Such effects are associated with antioxidative/oxidative reactions as indicated by the biomarkers SOD, POD, CAT, and MDA.  相似文献   

9.
Licorice has been used as an antitussive and expectorant herbal medicine for a long history. This work evaluated the activities of 14 major compounds and crude extracts of licorice, using the classical ammonia-induced cough model and phenol red secretion model in mice. Liquiritin apioside (1), liquiritin (2), and liquiritigenin (3) at 50?mg/kg (i.g.) could significantly decrease cough frequency by 30–78% (p?<?.01). The antitussive effects could be partially antagonized by the pretreatment of methysergide or glibenclamide, but not naloxone. Moreover, compounds 13 showed potent expectorant activities after 3?days treatment (p?<?.05). The water and ethanol extracts of licorice, which contain abundant 1 and 2, could decrease cough frequency at 200?mg/kg by 25–59% (p?<?.05), and enhance the phenol red secretion (p?<?.05), while the ethyl acetate extract showed little effect. These results indicate liquiritin apioside and liquiritin are the major antitussive and expectorant compounds of licorice. Their antitussive effects depend on both peripheral and central mechanisms.  相似文献   

10.
A/J strain mice have a high spontaneous incidence of cleft lip (ICL) and/or palate. The primary palate-related effects of sevoflurane on developing A/J strain mouse embryos (embryos) were studied using a whole-embryo culture (WEC) system. This system could separate the direct effects of sevoflurane from those that are maternally mediated. A total of 205 10.5-d embryos were cultured for 24 h in either a control group (control gas: 95% O2 and 5% CO2) or sevoflurane-administered groups (1/4, 1/2, and 1 minimum alveolar concentration (MAC) with control gas) for 8 h. After 16 h, 11.5-d culture embryos were examined in terms of crown-rump length, number of somites, and protein content. Crown-rump length in the 1 MAC was significantly shorter than in the control group (p?<?0.05). Protein content in the 1/2 MAC (p?<?0.05) and 1 MAC (p?<?0.001) was significantly lower than in the control group. The ICL showed no significant differences between each group. (The ICL rose with an increase in the sevoflurane concentration, but this was not significant). The positive findings in this study indicate that a WEC system is useful for studying the mechanisms of ICL (teratogenicity) associated with sevoflurane.  相似文献   

11.
The aim of this study was to assess the effects of graded levels (0, 3, 6, 9 and 12 g/kg) of dry Sea buckthorn (SB) berries on growth performance, gastrointestinal tract (GIT) development, jejunal histomorphology, bird antioxidant status and caecal short-chain fatty acid concentration when fed to female Ross 308 broiler chickens. In addition, expression of cytokine biomarker genes in the jejunum was evaluated. The five experimental diets were fed from 7 to 21 days age to 8 pens (two birds in each) following randomisation. Feeding SB did not influence bird growth performance (p > .05). There was a linear decrease in butyric, acetic and valeric acid concentrations in caecal digesta (p < .05) and a decrease (p < .05) in crypt depth. The expression of IFNG and CD40LG responded quadratically (p < .05), peaking at 6–9 g/kg dietary inclusion of SB, respectively. Other studied variables were not affected by dietary SB inclusion (p > .05). Feeding dry SB berries up to 12 g/kg of diet did not improve the zootechnical variables of healthy commercial-strain broilers in this study.  相似文献   

12.
Reactive oxygen species and lipid peroxidation reaction, causes of sperm damage, can be diminished by action of antioxidative enzymes. This study aimed to investigate effects of (1) the antioxidative enzymes; catalase, glutathione peroxidase and superoxide dismutase, on epipididymal cat sperm quality and (2) the lipid peroxidation reaction induced by a transition metal (ferrous ion (II); Fe2+) on sperm quality during the cryopreservation process. Epididymal spermatozoa harvested from 39 male cats were pooled and divided into 13 aliquots (n = 13). Each aliquot was resuspended with either a Tris egg yolk extender I (control; EE-I), or the Tris egg yolk extender I supplemented with 200 U/mL catalase (EE-CAT), or 10 U/mL glutathione peroxidase (EE-GPx), or 600 U/mL superoxide dismutase (EE-SOD), and then cryopreserved. After thawing, each sperm sample was subdivided into two groups; with and without lipid peroxidation induction (EE-I plus Fe2+, EE-CAT plus Fe2+, EE-GPx plus Fe2+ and EE-SOD plus Fe2+). Subjective sperm motility, membrane, and acrosome integrity were evaluated at the time of collection, after cooling, and at 0, 2, 4, and 6 h after thawing. Motility patterns assessed by computer-assisted sperm analysis (CASA), mitochondrial activity, and DNA integrity were evaluated during post-thaw incubation, whereas percentage of lipid peroxidation was detected at 0 and 6 h after thawing. The results demonstrate that catalase supplementation reduced linear motility and subjective motility immediately and 2 h after thawing (P < 0.05). Catalase supplementation, however, improved DNA integrity at 4 h (P < 0.05). Supplementation with glutathione peroxidase, compared to the control group, had a statistically significant positive effect on subjective motility at 0 and 6 h, linear motility at 6 h, mitochondrial activity at 6 h, membrane integrity at 2 and 6 h, and DNA integrity at 4 h after thawing. Although superoxide dismutase had a positive effect on sperm membrane integrity at 2 h after thawing (P < 0.05), it significantly reduced membrane integrity after cooling, linear motility at thawing, and acrosome integrity at 2 h after thawing. None of the three selected antioxidative enzymes significantly influenced acrosome integrity and none reduced the level of lipid peroxidation. Furthermore, induction of the lipid peroxidation reaction by Fe2+ negatively affected most of the sperm quality parameters, i.e., motility and DNA integrity, during post-thaw sperm incubation (P < 0.05). After thawing, there were, however, no significant differences between the control plus Fe2+ and the antioxidative enzymes supplementation plus Fe2+ groups. We can conclude that (1) glutathione peroxidase exhibits positive effects on post-thaw epididymal cat spermatozoa; but (2) none among the selected antioxidative enzymes could improve all sperm quality parameters; and (3) the lipid peroxidation reaction may be one cause of post-thaw epididymal sperm damage in cats, but the concentrations of antioxidative enzymes used in this study could not protect cat spermatozoa from lipid peroxidation induction.  相似文献   

13.
This study was aimed to investigate the effect of extremely low-frequency magnetic field (ELF-MF) on apoptosis and oxidative stress values in the brain of rat. Rats were exposed to 100 and 500 µT ELF-MF, which are the safety standards of public and occupational exposure for 2 h/day for 10 months. Brain tissues were immunohistochemically stained for the active (cleaved) caspase-3 in order to measure the apoptotic index by a semi-quantitative scoring system. In addition, the levels of catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidative capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were measured in rat brain. Final score of apoptosis and MPO activity were not significantly different between the groups. CAT activity decreased in both exposure groups (p?<?0.05), while TAC was found to be lower in ELF 500 group than those in ELF-100 and sham groups (p?<?0.05). MDA, TOS, and OSI values were found to be higher in ELF-500 group than those in ELF-100 and sham groups (p?<?0.05). In conclusion, apoptosis was not changed by long-term ELF-MF exposure, while both 100 and 500 µT ELF-MF exposure induced toxic effect in the rat brain by increasing oxidative stress and diminishing antioxidant defense system.  相似文献   

14.
We aimed to investigate the influence of dietary vitamin E and diludine on growth and lipid peroxidation (malondialdehyde; MDA) in rainbow trout. Fish (1.5 g) were fed different dietary levels of vitamin E (0, 50 and 100 mg/kg) and diludine (0, 0.5 and 1 g/kg) for 10 weeks. Growth performance and feed conversion ratio (FCR) were significantly affected by dietary vitamin E (p < .05) but not diludine. Fish fed 50 mg/kg dietary vitamin E with no diludine had significantly better growth and lower FCR than those fed vitamin E free diets. Liver vitamin E content was significantly influenced by dietary vitamin E and diludine (p < .05). The highest hepatic vitamin E was in fish fed the highest dietary vitamin E and diludine levels. Hepatic MDA level was significantly affected by dietary vitamin E and diludine (p < .05), decreasing with the increase in both dietary vitamin E and diludine. According to our results, diludine had no significant effect on growth; however, decreased hepatic lipid peroxidation independent of vitamin E. Our results reveal that 50 mg/kg vitamin E content is suitable for optimal growth and FCR in rainbow trout juveniles. However, dose dependent effects of dietary diludine remain uncertain and need further researches.  相似文献   

15.
The effect of exercise-induced oxidative stress on health and aging is not clearly explained. This study examined the effects of habitual sport practice, age, and submaximal exercise on the blood markers of oxidative stress, muscle damage, and antioxidant response. Seventy-two healthy men were grouped by their habitual sport practice: inactive (<1.5 h/week), recreational (3–8 h/week), and trained athletes (>8 h/week), and further divided by age: young (18–25 years), adult (40–55 years), and senior (>55 years). Blood samples were collected at rest and after submaximal effort. Hydroperoxides and superoxide dismutase, glutathione peroxidase, and catalase activities were measured by spectrophotometry. Nuclear DNA damage was analyzed by comet assay. The alpha-actin release was analyzed by Western blot. Alpha-tocopherol, retinol, and coenzyme-Q10 were quantified by high-performance liquid chromatography analysis. Data was analyzed through a factorial ANOVA and the Bonferroni post hoc test. Lipid peroxidation increased significantly with age and submaximal effort (p?<?0.05). However, the trained athlete group presented lower lipid peroxidation compared with the recreational group (MD?=?2.079, SED?=?0.58, p?=?0.002) and inactive group (MD?=?1.979, SED?=?0.61, p?=?0.005). Trained athletes showed significant higher alpha-actin levels (p?<?0.001) than the other groups. Recreational group showed lower nuclear DNA damage than trained athletes (MD?=?3.681, SED?=?1.28, p?=?0.015). Nevertheless, the inactive group presented significantly higher superoxide dismutase and catalase (p?<?0.05) than the other groups. Data suggested that habitual competitive training practice could prevent age-related increases of plasma lipid peroxidation, which, according with our results, cannot be entirely attributed to blood antioxidant defense systems.  相似文献   

16.
The study was conducted to investigate the effects of dietary maternal selenomethionine or sodium selenite supplementation on performance and selenium status of broiler breeders and their next generation. Two hundred and forty 39-week-old Lingnan yellow broiler breeders were allocated randomly into two treatments, each of which included three replicates of 40 birds. Pretreatment period was 2 weeks, and the experiment lasted 8 weeks. The groups were fed the same basal diet supplemented with 0.30 mg selenium/kg of sodium selenite or selenomethionine. After incubation, 180 chicks from the same parental treatment group were randomly divided into three replicates, with 60 birds per replicate. All the offspring were fed the same diet containing 0.04 mg selenium/kg, and the experiment also lasted 8 weeks. Birth rate was greater (p < 0.05) in hens fed with selenomethionine than that in hens fed with sodium selenite. The selenium concentration in serum, liver, kidney, and breast muscle of broiler breeders, selenium deposition in the yolk, and albumen and tissues' (liver, kidney, breast muscle) selenium concentrations of 1-day-old chicks were significantly (p < 0.01) increased by maternal selenomethionine supplementation compared with maternal sodium selenite supplementation. The antioxidant status of 1-day-old chicks was greatly improved by maternal selenomethionine intake in comparison with maternal sodium selenite intake and was evidenced by the increased glutathione peroxidase activity in breast muscle (p < 0.05), superoxide dismutase activity in breast muscle and kidney (p < 0.05), glutathione concentration in kidney (p < 0.01), total antioxidant capability in breast muscle and liver (p < 0.05), and decreased malondialdehyde concentration in liver and pancreas (p < 0.05) of 1-day-old chicks. Feed utilization was better (p < 0.05), and mortality was lower (p < 0.05) in the progeny from hens fed with selenomethionine throughout the 8-week growing period compared with those from hens fed with sodium selenite. In summary, we concluded that maternal selenomethionine supplementation increased birth rate and Se deposition in serum and tissues of broiler breeders as well as in egg yolk and egg albumen more than maternal sodium selenite supplementation. Furthermore, maternal selenomethionine intake was also superior to maternal sodium selenite intake in improving the tissues Se deposition and antioxidant status of 1-day-old chicks and increasing the performance of the progeny during 8 weeks of post-hatch life.  相似文献   

17.
In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4·5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p?<?0.05) or copper plus resveratrol (p?<?0.001) in comparison with the control groups that received the same diets. In cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p?<?0.001). The mean serum copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p?<?0.001). The characteristic changes in iron content and the zinc/copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research.  相似文献   

18.
The aim of the present work was to investigate the mechanisms of oxidative damage of rat liver mitochondria in vitro, under hypochlorous acid (HOCl)-induced oxidative stress, and in vivo, under acute carbon tetrachloride-induced intoxication in rats. Hypochlorous acid (50–300 μM), the main inflammatory agent, inhibited liver mitochondria respiratory activity and caused uncoupling in the respiratory and phos-porylation processes. The toxic damage of rat liver after 24 h of acute carbon tetrachloride-induced intoxication (4 g/kg, intragastrically) was accompanied by a significant reduction in succinate- and glutamate-dependent respiration rate in state 3 (by 65%, p < 0.001, and by 50%, p < 0.01, respectively). The respiration control ratio approached 1, reflecting the loss of respiration control. The phosphorylation coefficient significantly decreased due to uncoupling of the oxidation and phosphorylation processes. The mitochondrial alterations were associated with oxidation of intramitochondrial GSH by 25% (p < 0.05), the marked inhibition of succinate dehydrogenase (complex II) by 35% (p < 0.05), and the rise of blood plasma nitric oxide level by 45% (p < 0.05). The impairment of mitochondrial respiratory function may result from the inhibition of enzymatic activities in the respiratory chain and the damage of mitochondrial membrane during intoxication and plays a key role in the development of the CCl4-induced hepatotoxicity. Melatonin administration under CCl4-induced intoxication (three times at a dose of 10 mg/kg) increased the rate of succinate oxidation in state 3 by 30% (p < 0.05) and reversed the increase in glutathione peroxidase activity. Melatonin prevented an elevation of nitric oxide level in the blood plasma of intoxicated animals but did not protect mitochondrial functions under acute intoxication.  相似文献   

19.
Malaria is a global health problem leading to the death of 435,000 cases in tropical and sub-tropical zones. Spread and emergence of increasing resistance to the antimalarial drugs are the major challenges in the control of malaria. Therefore, searching for alternative antimalarial drugs is urgently needed, and combination treatment preferred as an approach to address this. This study aimed to evaluate in vivo antimalarial activity of zingerone (ZN), and its combination with dihydroartemisinin (DHA) against Plasmodium berghei infected mice. ZN was prepared and tested for acute oral toxicity according to the OECD guideline. In vivo antimalarial activity of different doses of ZN and combination with DHA were determined using the 4-day suppression test. The results showed that ZN was found to be safe and no mortality within the observation period, and the lethal dose might be greater than the limited dose of 1000 mg/kg. For in vivo antimalarial test, ZN exhibited significant (p < .05) parasitemia inhibition of 30.65% and 45.75% at the doses of 50 mg/kg and 100 mg/kg, respectively. Moreover, effective dose 50 (ED50) of ZN was 29.76 mg/kg. The combination treatment of ZN and DHA at the doses of ED50 values at the fixed ratio 1:1 was found to present significant (p < .001) antimalarial activity as compared to ZN and DHA treated alone with markedly prolonged mean survival time. Additionally, the combination index (0.83384) revealed the synergistic antimalarial effect. It can be concluded that ZN exerted potent antimalarial activity with no toxicity, and combination treatment with DHA produced the synergistic antimalarial effect.  相似文献   

20.
Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.  相似文献   

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