Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4-induced injuries in rats

ABSTRACT: BACKGROUND: Launaea procumbens (Asteraceae) is used as a folk medicine to treat hepatic disorders in Pakistan. The effect of a chloroform extract of Launaea procumbens (LPCE) was evaluated against carbon-tetrachloride (CCl4)-induced liver damage in rats. METHODS: To evaluate the hepatoprotective effects of LPCE, 36 male Sprague-Dawley rats were equally divided into six groups. Animals of group 1 (control) had free access to food and water. Group II received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for 4 weeks. Group III received 1 ml of silymarin via gavage (100 mg/kg b.w.) after 48 h of CCl4 treatment whereas groups IV and V were given 1 ml of LPCE (100 and 200 mg/kg b.w., respectively) after 48 h of CCl4 treatment. Group VI received 1 ml of LPCE (200 mg/kg b.w.) twice a week for 4 weeks. The activities of the antioxidant enzymes catalase, peroxidase (POD), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) were measured in liver homogenates. DNA damage, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology were studied in liver samples. Serum was analyzed for various biochemical parameters. Phytochemical composition in LPCE was determined through high-performance liquid chromatography (HPLC). RESULTS: LPCE inhibited lipid peroxidation, and reduced the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase in serum induced by CCl4. GSH contents were increased as were the activities of antioxidant enzymes (catalase, SOD, GST, GSR, GSH-Px) when altered due to CCl4 hepatotoxicity. Similarly, absolute liver weight, relative liver weight and the number of hepatic lesions were reduced with co-administration of LPCE. Phyochemical analyses of LPCE indicated that it contained catechin, kaempferol, rutin, hyperoside and myricetin. CONCLUSION: These results indicated that Launaea procumbens efficiently protected against the hepatotoxicity induced by CCl4 in rats, possibly through the antioxidant effects of flavonoids present in LPCE. KEYWORDS: Launaea procumbens, hepatic injuries, flavonoids, antioxidant enzymes, carbon tetrachloride.     

Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat

The present study was carried out to evaluate the antioxidant effect of the chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves in Sprague–Dawley male rats. The different groups of animals were administered with carbon tetrachloride (CCl₄; 20% in olive oil, 2 ml/kg body weight) 7 doses (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl₄ treated rats. The effect of CSCE or silymarin on urine and serum markers (urea, creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was measured in CCl₄-induced nephrotoxicity in rat. Further, the effects on lipid peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The CSCE and silymarin produced significant renal protective effects by restoring the concentration of urine and serum markers. Activity level of antioxidant enzymes and GSH contents were increased while lipid peroxidation (TBARS) was decreased, dose dependently with CSCE and silymarin. Decrease in body whereas increase in kidney weight induced with CCl₄ was restored with CSCE and silymarin. Chemical composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids and very low amount of saponins. Total flavonoids estimated were (127 ± 14.6) as rutin equivalent mg/g of the extract. From these results, it is suggested that CSCE possesses potent nephroprotective and antioxidant properties.     

Ameliorating effect of phytoestrogens on CCl4-induced oxidative stress in the livers of male Wistar rats

Glutathione-S-transferases and glutathione play a key role in the detoxification of most toxic agents. In the present study, the protective effects, if any, of isoflavone phytoestrogens--genistein and daidzein on the carbon tetrachloride (CCl4) induced changes in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione S transferase (GSH) and levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)-were studied. The activities of ALT and AST were assayed in the serum, whereas the activity of GST and levels of GSH and TBARS were determined in the livers of rats. The current study involved the division of animals into two main groups: (i) rats pretreated with genistein and daidzein for three days; and (ii) non-pretreated rats. In the pretreated group, rats received oral doses of genistein (7.9 micromol/kg body weight) and daidzein (7.9 micromol/kg body weight) for three consecutive days (once daily) followed by oral dose of CCl4 on the 4th and the 5th day concurrently with the phytoestrogens-genistein or daidzein. In the non-pretreated group animals received oral dose of CCl4 (1 ml/kg body weight) for two consecutive days along with the phytoestrogens-genistein or daidzein. Treatment of male rats with CCl4 significantly elevated the activity of ALT and AST in serum and levels of TBARS in the liver. On the other hand, CCl4 resulted in decreased activity of GST and lowered the GSH levels. Coadministration of genistein and daidzein with CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to normal control levels. However, repeated dose treatments with genistein and daidzein for three days prior to the administration of CCl4 restored such alterations to normal levels. Our results indicate that genistein is more effective than daidzein in counteracting the inhibition of GST activity caused by CCl4 and restoring it to normal levels. Genistein was also more effective than daidzein restoring the induced TBARS levels caused by CCl4 to normal control levels when rats were pretreated with the isoflavone orally for three days. It has been observed that the tested isoflavonoids were able to antagonize the toxic effects of CCl4. Such counteracting effects were more pronounced for genistein and when the phytoestrogens were administered as repeated doses prior CCl4 administration.     

Phytomedicinal activity of Terminalia arjuna against carbon tetrachloride induced cardiac oxidative stress.

Chronic and acute overproduction of reactive oxygen species (ROS) plays a positive role in the development of cardiovascular diseases under pathophysiological conditions. However, very little is known about carbon tetrachloride (CCl(4)) induced cardiac oxidative stress. The present study was conducted to find out CCl(4) induced oxidative insult in cardiac tissue and the cardioprotective effect of the 70% ethanol extractable active constituents of the bark of Terminalia arjuna (TA) against that stress in mice. Oral administration of CCl(4) at a dose of 1ml/kg body weight for 2 days significantly reduced the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), as well as depleted the level of reduced glutathione (GSH) in the cardiac tissue. In addition, extent of lipid peroxidation and the level of oxidized glutathione (GSSG) were increased under the same experimental conditions. Oral treatment of the active constituents of TA at a dose of 50mg/kg body weight for 7 days prior to CCl(4) administration significantly restored the activities of all antioxidant enzymes as well as increased the level of GSH and decreased the level of lipid peroxidation end products. In addition, FRAP assay showed that the active constituents of TA enhanced the cardiac intracellular antioxidant activity. Histological studies also supported the cardioprotective role of the active constituents. The active constituents-induced protective effect was compared with a known antioxidant, vitamin C. To the best of our knowledge, this is the first report describing the CCl(4) induced cardiac oxidative stress and cardioprotective action of the active phytoconstituents of Terminalia arjuna against that oxidative insult.     

Attenuation of CCl4-induced hepatic oxidative stress in rat by Launaea procumbens

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl₄-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl₄ (3 ml/kg b.w.; i.p., 20% CCl₄/olive oil) twice a week for four weeks. Group III received only CCl₄ while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl₄ in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, γ-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl₄. GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl₄. Hepatic lesions and telomerase activity induced with CCl₄ was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl₄-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.     

金丝桃苷对CCl4诱导大鼠急性肝损伤抗氧化应激研究

目的研究金丝桃苷（Hyp）对四氯化碳（CCI。）诱导大鼠急性肝损伤的治疗作用。方法采用大鼠CCl4急性肝损伤模型,观察Hyp对急性肝损伤大鼠肝脏组织病理学改变的影响;检测肝组织匀浆中超氧化物歧化酶（T-SOD）、谷胱甘肽（GSH）的活性及丙二醛（MDA）含量变化。结果CCl4模型组大鼠肝组织HE染色病理检测结果见明显炎症变性死及纤维组织增生现象;Hyp高剂量60mg／kg、中剂量30mg／kg治疗组的肝组织病理改变明显改善;Hyp治疗组肝组织中T—SOD、GSH活性明显升高,MDA含量明显降低,并存在量效关系。结论Hyp对CCl4引起的大鼠急性肝损伤有较好的治疗作用,其机制可能与其抗氧化活性有关。     

Protective effects of Wu-Ling-Shen (Xylaria nigripes) on carbon tetrachloride-induced hepatotoxicity in mice

Wu-Ling-Shen, a lesser study medicinal fungus (Xylaria nigripes), is popular for treating insomnia and trauma in the traditional Chinese medicine. In this study, our aim was to examine the protective effects of X. nigripes extract on carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in mice, and its content of polyphenolic constituents. The X. nigripes aqueous extract (XN-T) at 500 and 1000?mg/kg was given intragastrically to mice for 9 consecutive days, followed by receiving subcutaneously 2?mL/kg of 40% CCl(4) in olive oil to induce hepatotoxicity. Blood and liver tissues were collected for biochemical and histological analyses. Analysis of polyphenolic compounds was performed by RP-HPLC. Results showed that XN-T at 500 and 1000?mg/kg significantly prevented the elevation of serum glutamate oxalate transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT), and liver thiobarbituric acid reactive substances (TBARS) levels, and caused an increase in the liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) concentrations, as well as serum total antioxidant activity in the CCl(4)-induced hepatotoxicated mice. It was as good as silymarin (100?mg/kg) in normalization of oxidative stress parameters. Furthermore, liver histological observation also showed an obvious amelioration in the liver conditions in XN-T-treated animals. XN-T was found to contain a higher level of epicatechin, catechin, and p-coumaric acid. These results conclude that XN exerts effective protection against CCl(4)-induced liver injury in mice, and its mechanism of action could be through the effects of antioxidants on reducing the oxidative stress.     

Hepatoprotective effect of the natural fruit juice from Aronia melanocarpa on carbon tetrachloride-induced acute liver damage in rats.

The fruits of Aronia melanocarpa are rich in anthocyanins--plant pigments with anti-inflammatory and antioxidant activity. We studied the effect of the natural fruit juice from A. melanocarpa (NFJAM) on carbon tetrachloride (CCl4)-induced acute liver damage in rats. Histopathological changes such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins occurred in rats following acute exposure to CCl4 (0.2 ml kg(-1), 2 days). The administration of CCl4 increased plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, induced lipid peroxidation (as measured by malondialdehyde (MDA) content in rat liver and plasma) and caused a depletion of liver reduced glutathione (GSH). NFJAM (5, 10 and 20 ml kg(-1), 4 days) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities, induced by CCl4 (0.2ml kg(-1), 3rd and 4th days). NFJAM also prevented the CCl4-induced elevation of MDA formation and depletion of GSH content in rat liver.     

Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress.

Artichoke is a plant with antioxidant properties. In this study, we investigated the effect of artichoke extract pretreatment on carbon tetrachloride (CCl(4))-induced oxidative stress and hepatotoxicity. Rats were given artichoke leaf extract (1.5g/kg/day) by gavage for 2 weeks and after then CCl(4) (1ml/kg; i.p.) was applied. All rats were killed 24h after the CCl(4) injection. CCl(4) administration resulted in hepatic necrosis and significant increases in plasma transaminase activities as well as hepatic malondialdehyde (MDA) and diene conjugate (DC) levels in the liver of rats. Glutathione (GSH) and vitamin C levels decreased, but vitamin E levels increased in the liver of CCl(4)-treated rats. Hepatic superoxide dismutase (SOD) activities remained unchanged, but glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities decreased following CCl(4) treatment. In rats pretreated with artichoke extract, significant decreases in plasma transaminase activities and amelioration in histopathological changes in the liver were observed following CCl(4) treatment as compared to CCl(4)-treated rats. In addition, hepatic MDA and DC levels decreased, but GSH levels and GSH-Px activities increased without any change in other antioxidant parameters following CCl(4) treatment in artichoke-pretreated rats. The present findings indicate that in vivo architoke extract administration may be useful for the prevention of oxidative stress-induced hepatotoxicity.     

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: A novel study

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague–Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl₄ treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl₄, were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl₄ in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl₄-induced oxidative damage in rats.     

Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes.

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.     

The impact of propylthiouracil therapy on lipid peroxidation and antioxidant status parameters in hyperthyroid patients

This study was performed on 17 hyperthyroid patients and 15 healthy controls. The patients were under propylthiouracil (PTU) therapy at a dosage of 3 x 100 mg/day for one month. Blood samples, taken at the beginning and on the 30th day of therapy, were analyzed for hormonal parameters (T3, T4, TSH), lipid peroxidation endproduct [thiobarbituric acid reactive substances (TBARS)] and antioxidant status parameters: glutathione (GSH), glutathione peroxidase (GSH-Px) and CuZn superoxide dismutase (CuZn SOD). Hyperthyroid patients were observed to have significantly higher TBARS, GSH and CuZn SOD levels than controls (P < 0.05, P < 0.001, P < 0.001, respectively). PTU therapy caused a relief in oxidative stress as reflected by significantly decreased TBARS levels (P < 0.001) and a selective modification in the antioxidant status parameters: significant decreases in GSH and CuZn SOD levels (P < 0.001) and a significant increase in GSH Px (P < 0.01) activity. Our findings suggest a selective modification of the antioxidative profile in hyperthyroidism. PTU should also be considered as an in vivo antioxidant, in addition to its antithyroid action.     

Overloaded training increases exercise-induced oxidative stress and damage.

We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study.     

Oxidative stress and changes in liver antioxidant enzymes induced by experimental dicroceliosis in hamsters

The purpose of our study was to assess the effects of experimental dicroceliosis on the antioxidant defense capability of the liver in hamsters. Studies were carried out at 80 and 120 days after infection with an oral dose of 40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was ascertained by the presence of fluke eggs in feces, increased serum ALT and AST activities, and histological findings. The concentration of thiobarbituric acid-reactive substances (TBARS) and the ratio of oxidized to reduced glutathione (GSSG/GSH), measured as markers of oxidative stress, were significantly increased [TBARS: +40% and +84% at 80 and 120 days postinfection (p.i.), respectively; GSSG/GSH: +200% and +117%]. Dicroceliosis increased Se-dependent glutathione peroxidase (GPx) activity in both cytosol (+24% and +46%) and mitochondria (+73% and +41%). Superoxide dismutase activity was significantly reduced in cytosol (−19% and −38%) and mitochondria (−20% and −39%). No significant change was found in the activity of Se-independent GPx or catalase. The ratio of glutathione peroxidase/glutathione reductase at 80 and 120 days p.i. was increased by 25% and 63%, respectively. Gamma-glutamyl cysteinyl synthetase activity was increased by 27% and 20%, respectively. Our data indicate that although dicroceliosis courses with activation of antioxidant enzymes and glutathione synthesis, inefficient scavenging of reactive oxygen species takes place, resulting in oxidative liver damage. Received: 1 November 1998 / Accepted: 17 December 1998     

Lycopene attenuates oxidative stress and heart lysosomal damage in isoproterenol induced cardiotoxicity in rats: A biochemical study

The present study was designed to investigate the cardioprotective potential of lycopene (LYC) on isoproterenol (ISO)-induced oxidative stress and heart lysosomal damage in rats. Male Sprague Dawley rats were pretreated with LYC (4mg/kg, p.o.) once daily for 21 days. After the treatment period, ISO (85mg/kg) was injected subcutaneously, once daily, to rats for 2 days. Hemodynamic parameters, cardiac marker enzymes, antioxidant, and oxidative stress parameters in serum and heart tissues were measured. ISO treated rats showed significant changes in heart rates, heart weights and serum lipid profiles. The activity of aspartate aminotranferase (AST), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) were increased significantly (p<0.01) in the serum of ISO rats. The levels of lipid peroxides (thiobarbituric acid reactive substances, TBARS), protein carbonyl content (PCC) and neutrophil infiltration marker; myeloperoxidase (MPO) were significantly (p<0.01) increased. In addition, the activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase, and cathepsin-d) in the serum and heart of ISO rats were increased significantly. Furthermore, a marked decrease in the levels of serum and cardiac reduced glutathione (GSH), vitamin C and cardiac enzymatic antioxidants; superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were observed. In vitro study confirmed the strong antioxidant effect of LYC on total antioxidant activity. In conclusion, the present study demonstrated that LYC supplementation to ISO rats significantly ameliorated lysosomal membrane damage as well as the alterations in cardiac enzymes, lipid profile and oxidative stress markers. These findings revealed the cardioprotective effects of LYC against ISO-induced oxidative stress and cardiotoxicity in rats. These observed effects are mediated via antioxidant power and free radical scavenging activity of LYC.     

肠缺血再灌注时肠粘膜抗氧化系统及肝、肾功能改变的实验研究

目的：研究肠缺血再灌注损伤时肠粘膜抗氧化系统的改变及对肝、肾功能的影响。 方法： 复制大鼠肠缺血再灌注模型，采用分光光度计生化测定方法检测肠粘膜的还原型谷胱甘肽GSH、谷胱甘肽-S-转移酶GST、过氧化氢酶CAT、丙二醛MDA、超氧化物岐化酶SOD、谷胱甘肽过氧化物酶GSH-Px及血清谷丙转氨酶ALT、谷草转氨酶AST、尿素氮BUN、肌酐Cr的改变。 结果： 肠粘膜MDA含量于再灌注2 h显著高于假手术组(P<0.05)，再灌注4 h较假手术组高116%(P<0.05)，24 h较前有所降低但仍高于假手术组(P<0.05)；GSH含量于再灌注2 h显著低于假手术组(P<0.05)，再灌注4 h低至假手术组的40%（P<0.01），12 h恢复；肠粘膜CAT、SOD和GSH-Px活性未见明显改变；GST活性于再灌注2 h较假手术组低39%，再灌注4 h达最低，较假手术组低43%(P<0.05)，12 h恢复至假手术组水平；血清ALT、AST、 BUN及Cr于再灌注2 h显著高于假手术组(P<0.05)，再灌注4 h分别较假手术组高208%、100%、103%、41%（P<0.01），24 h基本恢复。 结论： 肠缺血45 min再灌注使肠粘膜GSH含量和GST活性降低，MDA含量增加，并造成肝肾功能的可逆性损伤。     

The effects of hormone replacement therapy on lipid peroxidation and antioxidant status

OBJECTIVE: A number of studies have consistently shown a lower cardiovascular risk in women who received postmenopausal hormone replacement therapy (HRT). The aim of our study was to examine the effects of HRT on lipid peroxidation and antioxidant status, which were likely to be involved in the pathophysiology of atherosclerosis. METHODS: We measured erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels as expression of lipid peroxidation-end product malondialdehyde, and also erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity as indicators of the antioxidant status of the 35 postmenopausal women with HRT (mean age: 51.81 +/- 4.57 yr; body mass index (BMI): 26.56 +/- 3.78 kg/m(2)) and 35 postmenopausal women without HRT (mean age: 47.50 +/- 3.64; BMI: 27.42 +/-3.43 kg/m2). RESULTS: In the group with HRT, erythrocyte and plasma TBARS levels were significantly lower than in the group without HRT (P < 0.003 and P < 0.001, respectively). Erythrocyte GSH level and GSH-Px activity was found to be increased significantly in the group with HRT in comparison with the group without HRT (P < 0.001 and P < 0.001, respectively). There was not any correlation between the erythrocyte and plasma TBARS and erythrocyte GSH levels and GSH-Px activity with duration of HRT (mean 3.5+/-1.3 yr). CONCLUSION: Our results show that HRT is beneficial in the protection against oxidative damage and can prevent atherosclerotic complications.     

Curcumin regulates gene expression of insulin like growth factor,B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats

Background

The effects of curcumin on the activities and gene expression of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (G-ST), B-cell CLL/lymphoma 2 (Bcl-2) and insulin like growth factor-1 (IGF-1) in diabetic rats were studied.

Methods

Twenty four rats were assigned to three groups (8 rats for each). Rats of first group were non diabetic and rats of the second group were rendered diabetic by streptozotocin (STZ). Both groups received vehicle, corn oil only (5 ml/kg body weight) and served as negative and positive controls, respectively. Rats of the third group were rendered diabetic and received oral curcumin dissolved in corn oil at a dose of 15 mg/5 ml/kg body weight for 6 weeks.

Results

Diabetic rats showed significant increase of blood glucose, thiobarbituric acid reactive substances (TBARS) and activities of all antioxidant enzymes with significant reduction of reduced glutathione (GSH) compare to the control non diabetic group. Gene expression of Bcl2, SOD, CAT, GPX and GST was increased significantly in diabetic untreated rats compare to the control non diabetic group. The administration of curcumin to diabetic rats normalized significantly their blood sugar level and TBARS values and increased the activities of all antioxidant enzymes and GSH concentration. In addition, curcumin treated rats showed significant increase in gene expression of IGF-1, Bcl2, SOD and GST compare to non diabetic and diabetic untreated rats.

Conclusion

Curcumin was antidiabetic therapy, induced hypoglycemia by up-regulation of IGF-1 gene and ameliorate the diabetes induced oxidative stress via increasing the availability of GSH, increasing the activities and gene expression of antioxidant enzymes and Bcl2. Further studies are required to investigate the actual mechanism of action of curcumin regarding the up regulation of gene expression of examined parameters.

     

Prior treatment with captopril attenuates carbon tetrachloride-induced liver injury in mice

The present investigation focused on the possible hepatoprotective potential of captopril on carbon tetrachloride (CCl4)-induced acute liver injury in mice. Twenty-four hours after a single intraperitoneal injection of CCl4 (20 microl/Kg), hepatotoxicity was evidenced in the serum by elevated levels of aspartate transaminase (AST; EC: 2.6.1.1), alanine transaminase (ALT; EC: 2.6.1.2) and lactate dehydrogenase (LDH; EC: 1.1.1.27) and in the liver by depleted level of reduced glutathione (GSH), enhanced activity of glutathione peroxidase (GSH-Px; EC: 1I.11.1.9) and elevated level of lipid peroxides (LP). Captopril was given orally at three dose levels viz., 10, 25 and 50 mg/Kg/day for three consecutive days before subjecting the animals to the hepatotoxin. With the exception of the lowest dose namely, 10 mg/Kg/day, captopril afforded protection against CCl4-induced hepatotoxicity to different extents. Thus, the elevated activities of the enzymes AST, ALT, LDH and GSH-Px as well as the enhanced lipid peroxidation were markedly reduced below those elicited by the hepatotoxin, reaching values closer to the control, though still statistically higher. Captopril, however, did not ameliorate the depletion of GSH produced by CCl4. The data reported herein reveal a protective potential of captopril against the acute hepatotoxicity induced by CCl4 in mice. This hepatoprotection could be attributed, at least in part, to the free radical scavenging properties of the drug.     

Preventive Effect of Chrysin on Bleomycin-Induced Lung Fibrosis in Rats

The aim of the current study is determination of protective effect of chrysin (CRS), a natural flavonoid, on cell injury produced by lung fibrosis induced with bleomycin (BLC) in rats. Twenty-eight female rats were assigned to four groups as follows: control group, CRS group; 50 mg/kg CRS was continued orally for 14 days, BLC group; a single intratracheal injection of BLC (2.5 mg/kg body weight in 0.25 ml phosphate buffered saline), BLC?+?CRS group; 50 mg/kg CRS was administered 1 day before the intratracheal BLC injection and continued for 14 days orally. All animals were sacrificed at day 14th after BLC administration. The semiquantitative assessment of histopathological consisting of lung inflammation and collagen deposition, tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reducted glutathione (GSH) were measured. BLC provoked histological changes consisting of alveolar congestion, increase connective tissue, infiltration, and the thickness of alveolar wall were detected significantly when compared to the control group (p?≤?0.0001). CRS supplementation significantly restored these histological damages (p?≤?0.0001). The level of tissue TBARS was increased with BLC (p?GPx, CAT, and GSH in the lung tissue compared to control group (p?p?相似文献