Effect of fermented Panax ginseng extract (GINST) on oxidative stress and antioxidant activities in major organs of aged rats

The intracellular levels of oxidant and antioxidant balances are gradually distorted during the aging process. An age associated elevation of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The present study was undertaken to evaluate the putative antioxidant activity of the fermented Panax ginseng extract (GINST) on lipid peroxidation and antioxidant status of major organs of aged rats compared to young rats. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were observed in the serum of aged rats. Increased levels of malondialdehyde (MDA) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were observed in the liver, kidneys, heart and lungs of aged rats, when compared with those in young rats. Quantitative analysis of the non-enzymatic antioxidants such as reduced glutathione (GSH), ascorbic acid and α-tocopherol levels showed significantly lower values in the liver, kidneys, heart and lungs of aged rats. On the other hand, administration of the fermented Panax ginseng extract (GINST) to aged rats resulted in increased activities of SOD, CAT, GPx, GR and GST as well as elevation in GSH, ascorbic acid and α-tocopherol levels. Besides, the level of MDA, AST, ALT, urea and creatinine were reduced on administration of GINST to aged rats. These results suggested that treatment of GINST can improve the antioxidant status during aging, thereby minimizing the oxidative stress and occurrence of age-related disorders associated with free radicals.     

Prevention by melatonin of hepatocarcinogenesis in rats injected with N-nitrosodiethylamine

N-nitrosodiethylamine (NDEA) is a potent carcinogenic agent that induces liver cancer. To evaluate the chemopreventive function of melatonin in this experimental model, Wistar male rats received a single i.p. injection of NDEA or vehicle followed by weekly s.c. injections of carbon tetrachloride or vehicle for 6 weeks. Melatonin (5 mg/kg body weight) or its vehicle (0.5 mL saline) was given i.p. on a daily basis 2 hr before lights off for 20 wk. At the end of this period the rats were killed and liver and blood samples were taken for histological and biochemical studies. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein were measured in serum. To assess lipid peroxidation and the antioxidant status in liver and blood, the levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was assessed in liver and erythrocyte fraction of NDEA-treated rats. NDEA administration inhibited body weight, macro- and microscopically detectable liver tumors and increased levels of plasma AST, ALT and alpha-fetoprotein. NDEA treatment decreased liver TBARS levels and CAT and SOD activities and increased liver GSH levels and GST and GPx activities. Plasma TBARS were augmented, while plasma GSH levels and the activities of erythrocyte CAT, SOD, GST and GPx decreased, in NDEA-treated rats. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects.     

The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats

Objective:This study was performed to investigate the protective effect of Thymus vulgaris(T.vulgaris) leaves 70%alcoholic extract against alcohol-mediate hepatotoxicity rats.Methods:The protective effect of extract was investigated at dose of 500 mg/kg/day orally against alcohol-mediate hepatotoxicity using adult male Wister albino rats during 21 days.Protective effect of T.vulgaris extract was evaluated comparing with silymarin standard drug al recommended dose(25 mg/kg/day) orally for 21 days.Results:Alcohol-mediate hepatotoxicity rats(alcohol-control) showed hepatocytes distortion represented as marked increment on liver biomarkers;alkaline phosphatase(ALP),aspartate transaminase(AST) and alanine transaminase(ALT) activities,as well as pronounced reduction on total protein and its fractions albumin and globulin corresponding to normal ranges.Addition to oxidative stress status as depletion on glutathione concentration,catalase(CAT),superoxide dismutase(SOD),glutathione reductase(GR),glutathione-S-transferase(GST) and glutathione peroxidase(GPx)activities,concurrence with augmentation oxidative stress parameters;malondyaldchydc(MDA) and hydrogen peroxide(H_2O_2) concentrations comparing to normal values.Alcohol administration elevated total cholesterol(TC),low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol(HDL-C) comparing to normal ranges.Co-administration T.vulgaris extract with alcohol showed protective effect on hepatocytes manifested as minimizing on ALP.AST and ALT activities and increment on total protein,albumin and globulin production compared to alcohol-control.Antioxidant enzymes activities;CAT.SOD.GR,GST and GPx were significantly magnified,while MDA and H_2O_2 concentration were lessened corresponding to alcohol-control.Also,lipid profile was markedly improved and risk ratio was lowered compared to alcohol-control.These results were confirmed by normalization of degenerated and fibrotic liver tissue as of alcohol-control.Conclusion:T.vulgaris extract appeared hepatoprotective,hypolipidemic and antioxidant activities on alcohol-mediate hepatotoxicity rats compared to silymarin.     

Preventive and curative effect of methanolic extract of Gardenia gummifera Linn. f. on thioacetamide induced oxidative stress in rats

ObjectiveTo evaluate the antioxidant and antihepatotoxic effect of methanolic extract of Gardenia gummifera Linn. f. root (MEGG) on thioacetamide (TAA) induced oxidative stress in male Wistar rats.MethodsIn the preventive study, rats were administered with 125 and 250 mg/kg of MEGG for 9 days prior to TAA administration (100 mg/kg s.c.). In post-treatment groups, rats were treated with MEGG at doses of 125 and 250 mg/kg, 2, 24 and 48 h after TAA intoxication. Silymarin was used as a standard drug control (100 mg/kg). Hepatotoxicity was assessed by quantifying the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant potential of MEGG was evaluated by the estimation of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] in hepatic and renal tissues. Histopathological changes were also evaluated.ResultsMEGG significantly (P≤0.05) prevented the elevation of serum AST, ALT, ALP, LDH and tissue malondialdehyde levels in both experimental groups, when compared to the TAA alone treated groups. The rats receiving TAA plus MEGG exhibited significant (P≤0.05) increases in hepatic and renal antioxidant activities including GSH, GST, GR, GPx and CAT levels. Quantification of histopathological changes also supported the dose dependent protective effects of MEGG.ConclusionsThese observations suggest that MEGG has dose dependent hepatoprotective and antioxidant effect against TAA induced oxidative stress.     

The effect of carnosine treatment on prooxidant–antioxidant balance in liver,heart and brain tissues of male aged rats

Carnosine (β-alanyl-l-histidine) is a dipeptide with antioxidant properties. Oxidative damage by free radicals is one of the mechanisms underlying the aging process. This study was done to investigate the effects of carnosine treatment on lipid peroxidation and antioxidant status of liver, heart, brain in male young and aged rats. At the initiation of study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to rats. At the end of this period, malondialdehyde (MDA) and diene conjugate (DC) and protein carbonyl (PC) levels, glutathione (GSH), vitamin E and vitamin C levels and Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined in tissues of carnosine-treated young and old rats. Liver and heart, but not brain MDA and DC levels increased significantly in aged rats as compared to young rats. Liver PC levels were also significantly elevated. Significant decreases in GSH and vitamin C levels and SOD activities were detected in liver of aged rats, but vitamin E levels and GSH-Px and GST activities remained unchanged. Non-enzymatic and enzymatic antioxidants did not change in heart and brain of aged rats. Carnosine treatment decreased high MDA, DC and PC levels and caused significant increases in vitamin E level and SOD activity in the liver of aged rats. There were no changes in non-enzymatic and enzymatic antioxidants in the heart and brain of carnosine-treated aged rats. In conclusion, carnosine treatment was found to be useful in the decrease of age-related oxidative stress in the liver.     

Protective effect of an extract of the oyster mushroom, Pleurotus ostreatus, on antioxidants of major organs of aged rats

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on lipid peroxidation and antioxidant status of major organs of aged (24 month old) rats when compared to young (4 month old) rats. Elevated levels of malondialdehyde (MDA) and significantly lowered levels of reduced glutathione (GSH) and of vitamins C and E were observed in the liver, kidneys, heart and brain of aged rats, when compared to values in young rats. Quantitative analysis of the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) revealed significantly lower values in the liver, kidneys, heart and brain of aged rats. An analysis of isozyme pattern of these enzymes in aged rats also revealed variations in relative concentration, presumably due to oxidative stress. Administration of the extract of P. ostreatus to aged rats resulted in elevated levels of reduced glutathione and vitamins C and E and in increased activities of CAT, SOD and Gpx so that the values in most of these parameters did not differ significantly from those in young rats. In addition, the level of MDA was lowered on administration of mushroom extract to aged rats. These results suggest that treatment with an extract of P. ostreatus can improve the antioxidant status during ageing, therein minimizing the occurrence of age-associated disorders associated with involvement of free radicals.     

Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: Modulation by melatonin

Oxidative stress is an important factor for aging. The antioxidative enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and superoxide dismutase (SOD) play a crucial role protecting the organism against the age-dependent oxidative stress. Glutathione (GSH) is present in nearly all living cells. GSH is one of the main antioxidants in the cell and it serves several physiological functions. Our purpose was to evaluate the age-related changes in mitochondrial GPx, GRd and SOD activities, and mitochondrial GSH pool in the brains of young (3months) and aged rats (24months). We also investigated whether melatonin administration influences these brain mitochondrial enzyme activities and GSH levels in young and aged rats. The results showed that GPx activity increased with age, whereas melatonin treatment decreased GPx activity in the aged rats at levels similar to those in young and young+melatonin groups. The activities of GRd and SOD, however, did not change with age. But, melatonin treatment increased SOD activity in the aged rats. GSH levels, which also increased with age, were not modified by melatonin treatment. The reduction in the SOD/GPx and GR/GPx ratios with age was prevented by melatonin administration. Together, our results suggest that the age-related oxidative stress in rat brain mitochondria is more apparent when the antioxidant enzyme ratios are analyzed instead of their absolute values. The antioxidative effects of melatonin were also supported by the recovery of the enzyme ratios during aging.     

Protective effect of Mollugo nudicaulis Lam. on acute liver injury induced by perchloroethylene in experimental rats

ObjectiveTo evaluate the protective effect of ethanol extract of Mollugo nudicaulis (M. nudicaulis) against perchloroethylene-induced hepatotoxicity.MethodsThe hepatoprotective activity of the ethanol extract of M. nudicaulis (200 mg/kg body wt) was studied in percholoroethylene (1 000 mg/kg body wt) induced hepatotoxicity in Wistar albino rats. The serum levels of AST, ALT, ALP, bilirubin and the liver content of SOD, CAT, GPx, GST, GSH, vitamin C were assessed to evaluate the hepatoprotective and antioxidant activities of the extract. The activity of the extract was compared with silymarin, a standard reference drug. In addition, serum urea, uric acid and creatinine levels were measured to evaluate the kidney function. The histopathological examination of the liver tissues was observed to support the biochemical parameters.ResultsThe results revealed that the extract significantly (P<0.05) restored the serum levels of AST, ALT, ALP, bilirubin and significantly (P<0.05) increased the antioxidant enzymes SOD, CAT, GPx, GST, GSH, vitamin C in perchloroethylene-induced rats to its normalcy. The biochemical observations were supported by the histopathological studies of the liver tissues.ConclusionsThe results led to the conclusion that M. nudicaulis possess hepatoprotective and antioxidant activites against perchloroethylene-induced hepatotoxicity in rats.     

Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver

A central clock/pacemaker, suprachiasmatic nuclei of the hypothalamus coordinates and entrains circadian oscillations in the peripheral tissues such as the liver, kidney, heart, lungs etc. called peripheral clocks. These also have endogenous circadian oscillations. The circadian rhythms of antioxidants present in cytosol signify redox state of the cell during day/night cycle. The liver has a major impact on homeostasis through its control on serum protein composition and plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products and undergoes substantial changes in structure and function upon aging. In present study, the temporal patterns of oxidative stress indicators in liver were studied. Daily rhythms of lipid peroxidation end products, reduced glutathione (GSH), oxidized glutathione (GSSG) and antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were studied in liver at variable time points (Zeitgeber Time (ZT) 0, 6, 12 and 18) in three age groups: 3 (adult), 12 and 24?months old male Wistar rats. There was increase in oxidative stress in 12 and 24?months old rats indicated through a significant increase in lipid peroxidation, decrease in GSH/GSSG ratio and antioxidant enzyme activities. In 3?months old rats, lipid peroxidation was maximum at ZT-12 whereas GSH, SOD and CAT activities were minimum at ZT-12. The maximum level in 24?h i.e., acrophases of lipid peroxidation, GPx, SOD and CAT activities in liver cell free extracts altered upon aging. As melatonin, messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging we studied the effects of melatonin on activities of these antioxidant enzymes in aging rats. Melatonin administration resulted in differential restoration of acrophases, amplitude, mean as well as daily rhythms of lipid peroxidation and antioxidants in liver of 12 and 24?months old rats.     

Efficient hepatoprotective activity of cranberry extract against CCl_4-induced hepatotoxicity in Wistar albino rat model: Down-regulation of liver enzymes and strong antioxidant activity

Objective: To investigate the hepatoprotective efficacy of cranberry extract(CBE)against carbon tetrachloride(CCl4)-induced hepatic injury using in-vivo animal model.Methods: The hepatoprotective efficacy of CBE(200 and 400 mg/kg) was investigated against CCl4(4 m L/kg)-induced hepatotoxicity, elevated liver enzymes [ALT(alanine aminotransferase), AST(aspartate aminotransferase), and alkaline phosphatase(ALP)],and total protein(TP) contents in the serum. Moreover, CBE-aided antioxidant defense against hepatotoxic insult of CCl4 was measured by evaluating a number of anti-oxidative biomarkers including reduced glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), and malondialdehyde(MDA) in the serum by using spectrophotometric analyses.Results: Results showed that the exposure of experimental animals to CCl4 did induce significant hepatotoxicity compared to the non-induced(untreated) group. The oral administration of CBE demonstrated a significant dose-dependent alleviation in the liver enzymes(AST, ALT, and ALP), increased antioxidant defense(GSH, SOD, and CAT),and reduced MDA levels in the serum of treated animals compared to the animals without treatment. The resulting data showed that the administration of CBE decreased the serum levels of ALT, AST, and ALP compared to the CCl4-induced group.Conclusions: The resulting data evidenced that CBE exhibits promising hepatoprotective potential against the chemical induced hepatotoxicity, maintains homeostasis in liver enzymes, and can provide significant antioxidant defense against free radicals-induced oxidative stress.     

Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia

This study aimed to assess antioxidant effects of melatonin treatment compared to N‐acetylcysteine (NAC) and to their combination in a sickle cell suspension. Sickle erythrocytes were suspended in phosphate‐buffered saline, pH 7.4, composing external control group. They were also suspended and incubated at 37°C either in the absence (experimental control group) or in the presence of NAC, melatonin and their combination at concentrations of 100 pm , 100 nm and 100 μm for 1 hr (treatment groups). The melatonin influences were evaluated by spectrophotometric [hemolysis degree, catalase (CAT), glutathione S‐transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), glucose‐6‐phosphate dehydrogenase (G6PDH), and superoxide dismutase (SOD) activities] and chromatographic methods [glutathione (GSH) and malondialdehyde (MDA) levels]. Incubation period was able to cause a rise about 64% on hemolysis degree as well as practically doubled the lipid peroxidation levels (P < 0.01). However, almost all antioxidants tested treatments neutralized this incubation effect observed in MDA levels. Among the antioxidant biomarkers evaluated, we observed a modulating effect of combined treatment on GPx and SOD activities (P < 0.01), which showed ~25% decrease in their activities. In addition, we found an antioxidant dose‐dependent effect for melatonin on lipid peroxidation (r = ?0.29; P = 0.03) and for combined antioxidant treatments also on MDA levels (r = ?0.37; P = 0.01) and on SOD activity (r = ?0.54; P < 0.01). Hence, these findings contribute with important insight that melatonin individually or in combination with NAC may be useful for sickle cell anemia management.     

甜菜碱对酒精性肝损伤大鼠高同型半胱氨酸血症和肝脂质过氧化的影响

目的：观察甜菜碱对大鼠高同型半胱氨酸血症（hyperhomoeysteinemia，HHcy）和肝脏脂质过氧化的作用和影响。方法：将60只SD大鼠随机分为5组（每组12只）：正常对照组，模型组，甜菜碱低、高剂量组，腺苷蛋氨酸（S-adenosylmethionine，SAM）组。除对照组外，其余4组给予酒精、鱼油灌胃配合高脂饮食构建酒精性肝损伤大鼠模型，药物治疗于造模4周后开始，第8周处死全部大鼠，测定血浆总同型半胱氨酸（total plasma homoeysteine，tHcy）浓度、血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、白蛋白（Alb）、白／球蛋白比值（A／G）、肝匀浆丙二醛（MDA）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）含量，并进行肝脏病理组织学检查。结果：与对照组比较，模型组大鼠tHcy、ALT、AST、MDA含量均明显升高（P〈0．01），SOD、GSH水平明显降低（P〈0．01）。与模型组对比，甜菜碱低、高剂量组大鼠tHcy、ALT、AST、MDA均显著降低（P〈0．01），肝组织SOD含量明显上升（P〈0．01），GSH含量无显著变化（P〉0．05），甜菜碱低、高剂量组之间无明显差异（P〉0．05）；SAM组能显著增加肝组织GSH贮量（P〈0．01），但对血浆tHcy水平无显著影响（P〉0．05），余治疗作用均与甜菜碱治疗无显著差别（P〉0．05）。结论：甜菜碱可防治酒精性肝损伤，其机制可能为降低高同型半胱氨酸血症，改善肝组织脂质过氧化。本文结果显示，甜菜碱的作用优于腺苷蛋氨酸。     

补肾养肝合剂对四氯化碳诱导大鼠急性肝损伤的防护作用

目的：探讨补肾养肝合剂萃取物对四氯化碳（CCl4）诱导大鼠急性肝损伤之影响。方法：用CCl4诱导急性肝损伤模型，造模前口服补肾养肝合剂萃取物（100，500mg／kg），适时检测血清中ALT、AST活性。结果：补肾养肝合剂可有效降低CCl4诱发之ALT、AST活性；提升肝脏中抗氧化酵素（酶）SOD、GPx、GR活性。结论：结果显示补肾养肝合剂萃取物对CCl4诱导急性肝损伤具有防护作用，其防护CCl4诱导急性肝损伤之机转与提升肝脏内抗氧化酵素（酶）GR、GPx与SOD活性有关。     

蓝莓预防大鼠肝损伤实验研究

目的探讨蓝莓对四氯化碳（CCl4）所致大鼠急性肝损伤的预防保护作用。方法SD大鼠随机分为蓝莓汁低、高两个剂量预防组、齐墩果酸阳性药对照组、正常对照组及模型组,采用CCl4致大鼠急性肝损伤模型。测定大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）以及肝组织匀浆超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）及丙二醛（MDA）,光镜下观察肝脏病理变化。结果蓝莓各剂量组及阳性对照组血清ALT及AST均明显低于模型组（P〈0．01）。与模型组比较,齐墩果酸组、蓝莓汁高剂量组肝匀浆GSH、SOD、CAT明显升高,MDA明显降低（P〈0．01或P〈0．05）;蓝莓汁低剂量组肝匀浆GSH升高不明显,肝匀浆SOD、CAT升高,MDA降低（P〈0．05）。结论蓝莓对CCl4所致大鼠急性肝损伤具有良好的预防保护作用,其机制可能与抗脂质过氧化作用有关。     

Melatonin stimulates the activity of protective antioxidative enzymes in myocardial cells of rats in the course of doxorubicin intoxication

The study aimed at determining the effect of melatonin on the activity of protective antioxidative enzymes in the heart and of lipid peroxidation products in the course of intoxication with doxorubicin (DOX). The rats were categorized into four groups, receiving: 0.9% NaCl i.p. (NaCl control); melatonin [20 mg/kg body weight (b.w.)] s.c. (control Mel); DOX (2.5 mg/kg b.w.) i.p.; melatonin plus DOX in doses as above. All the substances were administered once in a week for four consecutive weeks. Homogenates of heart tissue were examined for activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), levels of reduced glutathione (GSH) and of lipid peroxidation indices (MDA + 4-HDA). Administration of melatonin alone did not induce alterations in levels of MDA + 4-HDA, GSH, or in activity of GPx, SOD or CAT, as compared to the group receiving 0.9% NaCl. GSH levels decreased following DOX but remained at normal levels following DOX and melatonin. The level of MDA + 4-HDA increased following DOX, as compared with the control, a change prevented by the combination of DOX + melatonin. Activities of GPx, SOD and CAT were higher in groups receiving DOX and/or DOX plus melatonin than in control groups. Activity of CAT and the level of GSH in the group receiving DOX plus melatonin were significantly higher than in the group intoxicated with DOX alone. The obtained results demonstrate that, when given in parallel with DOX, melatonin protects cardiomyocytes from damaging effects of the cytostatic drug (reflected by the levels of MDA + 4-HDA). The protective effect resulted, in part from the augmented levels of GSH and from stimulation of CAT activity by melatonin in cardiomyocytes subjected to the action of DOX.     

Antioxidant and hepatoprotective effects of Ginkgo biloba phytosomes in carbon tetrachloride-induced liver injury in rodents.

AIM: The protective effects of Ginkgo biloba phytosomes (GBP) on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. METHODS: Liver damage was induced in Wistar rats by administering a 1:1 (v/v) mixture of CCl4 and olive oil (1 ml/kg, i.p.) once daily for 7 days. GBP at 25 mg/kg and 50 mg/kg, i.p. and reference drug silymarin (200 mg/kg, p.o.) were administered for 10 days to CCl4-treated rats, this treatment beginning 3 days prior to the commencement of CCl4 administration. The degree of protection was evaluated by determining the marker enzymes (SGOT, SGPT and SALP), albumin (Alb) and total proteins (TP). Further, the effects of GBP on lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were estimated in liver homogenates to evaluate antioxidant activity. RESULTS: GBP (25 and 50 mg/kg) and silymarin elicited significant hepatoprotective activity by decreasing the activities of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose-dependent manner. CONCLUSION: The present findings indicate that the hepatoprotective effects of GBP against CCl4-induced oxidative damage may be due to its antioxidant and free radical-scavenging activity.     

Effects of melatonin or acetylsalicylic acid on gastric oxidative stress after bile duct ligation in rats

Background Antioxidant enzyme activities decrease after bile duct ligation. The aim of this study was to assess the effect of melatonin and acetylsalicylic acid on antioxidant enzyme activities in gastric oxidative stress induced by bile duct ligation. Methods Sixty-four animals were divided into eight groups of eight rats each. Male Sprague-Dawley rats were subjected to either a sham operation or common bile duct ligation (BDL) before treatment with melatonin (MEL) or acetylsalicylic acid (ASA). Gastric superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) and nitric oxide (NO) levels were determined by spectrophotometers and evaluated. Results Our results indicated that BDL caused a significant increase in lipid peroxidation, whereas coadministration of MEL with ASA significantly decreased MDA and NO levels in BDL rats. Moreover, coadministration of MEL and ASA increased antioxidant enzyme activities after the BDL, and these increases were statistically significant for CAT and GPx. On the other hand, the increase in SOD activity was not significant. Conclusions Melatonin administration, either alone or together with acetylsalicylic acid, decreases lipid peroxidation and increases antioxidant enzyme activities in gastric tissues of rats after bile duct ligation. ASA administration, however, either alone or with a vehicle, increases lipid peroxidation and decreases antioxidant enzyme activities.     

Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats

This study compared the effects of melatonin supplementation on markers of oxidative stress, and on the activity and expression of antioxidant enzymes in the liver of young (3-month-old) and aging (24-month-old) rats. Animals were supplemented with melatonin in the drinking water (20 mg/L) for 4 wk. Liver concentration of thiobarbituric-reactive substances (TBARS), as an index of lipid peroxidation, and the oxidized to reduced glutathione ratio significantly increased in aged rats (+58%), while values did not significantly differ from the young in aged animals receiving melatonin. Significant decreases in the liver activities of Cu,Zn-superoxide dismutase (SOD) (-25%), cytosolic (-21%) and mitochondrial (-40%) glutathione peroxidase (GPx), and catalase (CAT) (-34%) were found in aged rats. Melatonin abolished these changes and also prevented the reduction of Cu,Zn-SOD (-33%), cytosolic GPx (-30%), and mitochondrial GPx (-47%) liver protein content as measured by Western blot. Reductions in Cu,Zn-SOD mRNA (-39%), and GPx mRNA (-86%) levels induced by aging were also abolished by melatonin. In summary, our data indicate that melatonin treatment abrogates oxidative stress in the liver of aged rats, and that prevention of the decreased activity of CAT and the downregulation of Cu,Zn-SOD and GPx gene expression contribute to this effect.     

Ultrastructural clues for the protective effect of melatonin against oxidative damage in cerulein-induced pancreatitis

The role of oxidative stress has been evaluated in experimental models of acute pancreatitis (AP). The aim of this study is to investigate the effect of melatonin on the ultrastructural changes in cerulein-induced AP in rats. Acute pancreatitis was induced by two i.p. injections of cerulein at 2-hr intervals (50 microg/kg BW). One group received additionally melatonin (20 mg/kg BW) i.p. before each injection of cerulein. The rats were sacrificed 12 hr after the last injection. Pancreatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides and changes in the antioxidant enzyme levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) levels. Ultrastructural examination was performed using a transmission electron microscope. Formation of numerous, large autophagosomes, mitochondrial damage, dilatation of rough endoplasmic reticulum (RER) and Golgi apparatus, margination and clumping of nuclear chromatin were the major ultrastructural alterations observed in the AP group. Melatonin administration prevented mitochondrial and nuclear changes and dilatation of RER and Golgi apparatus. Rare, small autophagosomes were present within the cytoplasm of some of the acinar cells. Pancreatic damage was accompanied by a significant increase in tissue MDA levels (P < 0.05) and a significant decrease in CAT, SOD, GPx activities and GSH levels (P < 0.005). Melatonin administration significantly reduced MDA levels but increased CAT, SOD, GPx activities and GSH levels (P < 0.005). Melatonin also reduced serum amylase and lipase activities, which were significantly elevated in AP (P < 0.05 and P < 0.005 respectively). These results suggest that oxidative injury is important in the pathogenesis of AP. Melatonin is potentially capable of limiting pancreatic damage produced during AP by protecting the fine structure of acinar cells and tissue antioxidant enzyme activities.     

Oxidant/antioxidant status in men with Behçet’s disease

Behçet’s disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to assess whether the increase in oxidative stress in the affected tissues is reflected by lipid peroxidation and to check for alterations in antioxidants and antioxidant enzyme activities in patients with BD. Erythrocyte antioxidant potential (AOP), glutathione (GSH) and GSH-dependent enzymes (glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST), catalase (CAT), Cu–Zn superoxide dismutase (Cu–Zn SOD) activities, malondialdehyde (MDA) and some trace elements (zinc, Zn; copper, Cu; manganese, Mn) levels in men with BD. Erythrocyte CAT, GSH-Px activities, MDA, GSH, AOP and serum Zn values were significantly lower in patients with BD than in the control group. However, erythrocyte Cu–Zn SOD, GRD activities, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and Cu values were significantly higher in patients with BD than in the control group, but GST activity and serum Mn values were unchanged. In conclusion, our results confirm the presence of oxidative stress in patients with BD and suggest that the severity of BD may arise from impaired antioxidant mechanisms. Therapy with antioxidants may lead to the increase in the antioxidant defense system and thus improvement in clinical symptoms.