Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats

Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats each [control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (P<0.001 and P<0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ-induced experimental diabetes and indicate the beneficial free radical-scavenging and antioxidant properties of melatonin.     

Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease.

AIMS: Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn-SOD and Mn-SOD), glutathione peroxidase (GPx), catalase) and non-enzymatic antioxidant systems. We aimed to determine, in patients with non-alcoholic fatty liver disease (NAFLD), the level of antioxidant defenses (1) in liver biopsies, to demonstrate the existence of oxidative stress; (2) in erythrocytes and plasma, to determine whether their antioxidant defenses reflect liver oxidative stress. METHODS: Erythrocyte and plasma antioxidant defenses were prospectively studied in two groups of 16 patients: patients with NAFLD and controls. Liver biopsies were performed in eight NAFLD patients; liver antioxidant enzyme activities were measured and compared with those in 12 control livers used for transplantation. RESULTS: Cu/Zn-SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn-SOD activity, and thiobarbituric acid-reactive substance (TBARS) concentration. No differences were observed in erythrocyte antioxidant enzyme activities (GPx, catalase, Cu/Zn-SOD), erythrocyte TBARS concentration, and plasma alpha-tocopherol concentration. CONCLUSIONS: Liver antioxidant enzyme activities were high in patients with NAFLD, reflecting an oxidative stress possibly involved in inflammation and fibrogenesis. However, erythrocyte and plasma antioxidant defenses did not reflect intrahepatic peroxidation.     

Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative stress in human hypertension

Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of beta-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress.     

Melatonin protects against piroxicam-induced gastric ulceration

The antiulcer effect of melatonin on gastric lesions caused by piroxicam was studied with the intent of determining the mechanism of action of this agent. Melatonin dose-dependently lowered piroxicam and indomethacin-induced gastric damage with more than 90% inhibition at a dose of 60 mg/kg BW. Increased lipid peroxidation, augmented protein oxidation and decreased glutathione content of the gastric tissue following piroxicam treatment indicated a possible involvement of oxidative stress in this nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Pretreatment of rats with melatonin prevented these changes. Oral administration of piroxicam to rats caused a threefold increase in the tissue levels of hydroxyl radical generation, a change significantly attenuated by melatonin. Furthermore, a decrease in the activity of gastric peroxidase and an increase in the activity of gastric superoxide dismutase(s) (SOD) because of piroxicam treatment was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. The results of the present studies also reveal that melatonin may influence the expression of Cu-Zn SOD, catalase, cyclooxygenase as well as alpha-actinin whose levels were found to be altered, following piroxicam treatment. The current studies, therefore, document melatonin's gastroprotective ability against piroxicam-induced gastric damage and the findings raise the possibility of melatonin being considered as a co-therapy with piroxicam or other NSAIDs in reducing the gastropathy when long-term use of these nonsteroidal agents are unavoidable.     

Antioxidant Enzyme Activities in Hepatic Tissue from Children with Chronic Cholestatic Liver Disease

Background/Aim:

To study the oxidative stress status in children with cholestatic chronic liver disease by determining activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in liver tissue.

Materials and Methods:

A total of 34 children suffering from cholestatic chronic liver disease were studied. They were selected from the Hepatology Clinic, Cairo University, and compared with seven children who happened to have incidental normal liver biopsy. The patients were divided into three groups: extrahepatic biliary atresia (n=13), neonatal hepatitis (n=15) and paucity of intrahepatic bile ducts (n=6); GPx, SOD and CAT levels were measured in fresh liver tissue using ELISA.

Results:

In the cholestatic patients, a significant increase was found in mean levels of SOD, GPx and CAT in hepatic tissue compared to control children. The three enzymes significantly increased in the extrahepatic biliary atresia group, whereas in the groups of neonatal hepatitis and paucity of intrahepatic bile ducts, only GPx and CAT enzymes were significantly increased.

Conclusion:

Oxidative stress could play a role in the pathogenesis of cholestatic chronic liver diseases. These preliminary results are encouraging to conduct more extensive clinical studies using adjuvant antioxidant therapy.     

Several antioxidant pathways are involved in astrocyte protection by melatonin

Neuroprotection provided by melatonin has been shown to be more relevant in vivo than in neuronal cultures. Given the role of astrocytes in neuronal support and protection, studies were initiated to elucidate the possible protective effect of the antioxidant melatonin against oxidative stress in these cells. Both low and high concentrations of melatonin were able to protect astrocytes with even higher efficiency than the known antioxidant glutathione (GSH). The mechanisms involved may be different for high (1 mm) and low (100 nm) concentrations of the indole. The GSH cycling appeared not to be involved in the protection at high doses. High doses of melatonin neither influenced GSH levels nor gene expression for the several antioxidant enzymes studied; thus, melatonin's protective effect was likely because of its free radical scavenging action in this case. However, melatonin concentrations in the nanomolar range require the presence of GSH to be effective. No increase in GSH synthesis was found, but low doses of melatonin increased gene expression and activity of glutathione peroxidase. As this enzyme requires GSH as substrate to be active, this may be the reason why the effect of this melatonin concentration is GSH dependent. In vivo, melatonin levels exhibit a wide range of concentrations with much lower levels in the blood and significantly higher concentrations in other body fluids and within cells. Thus, melatonin may normally function as an indirect and direct antioxidant in vivo.     

早发型与晚发型帕金森病患者血浆抗氧化应激指标分析

目的研究早发型与晚发型帕金森病(Parkinsons disease,PD)患者血浆抗氧化应激指标的差异性,并探讨其与临床特点的相关性。方法入选原发性PD患者62例(PD组),PD组根据发病年龄,分为早发型PD组35例和晚发型PD组27例;另入选健康体检者20例(对照组)。使用ELISA检测血浆谷胱甘肽(GSH)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)水平,比较各组间差异,并对发病年龄与血浆抗氧化应激指标进行相关性分析。结果 PD组患者血浆GSH[(18.42±14.64)μmol/L vs(79.32±64.48)μmol/L]、CAT[(160.87±10.49)kU/L vs(171.11±4.00)kU/L]、SOD[(93.58±24.17)kU/L vs(122.33±22.83)kU/L]水平明显低于对照组(P<0.01);早发型PD组患者血浆GSH水平明显高于晚发型PD组(P<0.05)。发病年龄与血浆GSH呈负相关(P<0.01)。结论 PD患者血浆GSH、CAT、SOD水平异常下降,提示PD患者存在抗氧化能力缺陷;早发型与晚发型PD患者血浆GSH水平具有显著差异性,发病年龄愈晚,血浆GSH水平愈低。     

Evidence of oxidative stress in chronic heart failure in humans

Chronic heart failure (CHF) due to coronary artery disease (CAD)has been shown to be associated with increased plasma thiobarbituricreactive substances (TBARS) and reduced plasma thiol (PSH) concentrations,suggesting oxidative stress (OS). The aims of the present studieswere (a) to determine whether OS is due to CAD or CHF per seand (b) to determine if a wider range of more specific markersof OS are abnormal in CHF. In the first study, two groups of patients (n = 15 each) werecompared. Group 1 (11 male, mean age 56 years) had CHF due toCAD and group 2 (12 male, mean age 53 years) had non-CAD CHF.Median plasma TBARS in controls was 7.6 nmol . ml^–1 ,10.0 nmol . m^–1 in group 1 and 9.3 nmol. ml^–1 ingroup 2 (P < 0.01 both groups vs control). Median PSH was505 384 and 364 nmol. ml^–1 (P < 0.05 and P < 0.01vs control) respectively. Fifty-three patients with CHF were recruited in the second study.Malondialdehyde and PSH were 10.3 and 409 nmol. ml^–1 respectively,compared to control values of 7.9 and 560 nmol. ml^.1 (both P< 0.001). The median values for the following additionalmeasures of OS in controls and patients were: erythrocyte superoxidedismustase 131 vs 114 U . l^–1 (P = 0.005); caeruloplasminoxidase 97 vs 197 U. l^–1 (P < 0.01); erythrocyte glutathione1.56 nmol . ml^–1 vs 1.77 nmol . ml^–1 (P < 0.02);plasma conjugated dienes 0.28 vs 0.33 optical density units(P = ns). Chronic heart failure, regardless of aetiology, is associatedwith abnormalities of a range of markers of OS.     

Melatonin protects against endosulfan-induced oxidative tissue damage in rats

Abstract:  Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)-induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor-α (TNF-α), interleukin-β (IL-β) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF-α and IL-β), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan-treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan-induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity.     

Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease

BACKGROUND: There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individuals with chronic liver disease and animal models of liver disease. Hence, by virtue of their increased presence in the circulation, it is not unreasonable to suppose that they may account for extrahepatic tissue damage in chronic liver disease. MATERIALS AND METHODS: This hypothesis was tested by determining plasma levels of the ubiquitous antioxidant glutathione (GSH) and lipid peroxides (LP), together with assessment of the extent of lipid peroxidation in the kidney, brain, and heart, in 24 day chronically bile duct ligated (CBDL) rats. The extent of lipid peroxidation in tissues was based on measurement of conjugated dienes, lipid peroxides, and malondialdehyde (MDA) content. Data were compared with identical data collected from unoperated control, pair fed, 24 day bile duct manipulated (sham operated), and pair fed sham operated rats. RESULTS: In CBDL rats, total and reduced plasma GSH levels were almost half those determined in all control rats. Plasma, kidney, and heart LP levels were significantly increased in CBDL rats compared with controls. MDA levels were significantly higher in the kidney, brain, and heart homogenates prepared from CBDL rats compared with MDA content measured in tissue homogenates prepared from the four groups of control rats. CONCLUSIONS: Our data show that experimental cholestatic liver disease is associated with increased lipid peroxidation in the kidney, brain, and heart. Hence we have concluded that the oxidative stress in cholestatic liver disease is a systemic phenomenon probably encompassing all tissues and organs, even those separated by the blood-brain barrier.     

Persistent Oxidative Stress in Patients with Chronic Active Hepatitis-C Infection After Antiviral Therapy Failure

Background/Aims:

Oxidative stress and hepatocellular pathological changes are common associations with chronic hepatitis C virus (CHC) disease. The aim of this study was to assess serum antioxidant-oxidant (Redox) balance in patients with CHC infection before and after intake of the traditional antiviral therapy (pegylated interferon α-2b and oral ribavirin).

Patients and Methods:

Blood samples from 50 biopsy-proven CHC patients, with no prior anti-viral treatment and persistently elevated serum transaminase levels for 6 months, as well as 15 age- and sex-matched healthy subjects were used for determination of the antioxidants: reduced glutathione (GSH), superoxide dismutase (SOD), α tocopherol and ascorbic acid as well as lipid peroxidation (LPO) index (malondialdehyde [MDA]). The measurements were repeated in the diseased group 25 weeks after pegylated interferon α-2b and ribavirin combination therapy.

Results:

Serum levels of bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly higher in CHC patients than in the control group (P < 0.05). Pretreatment serum MDA values were significantly higher in patients with CHC infection than the control group (P < 0.001), while serum antioxidant levels were significantly lower (P < 0.001). Responders (10 patients) had lower pretreatment serum levels of MDA than non-responders (35 patients) (P < 0.001). Both groups were comparable for the antioxidant serum levels. There was significant negative correlation between serum MDA and serum SOD, GSH, α tocopherol, and ascorbic acid concentrations in CHC patients. On the other hand, there was no correlation between the studied parameters and serum bilirubin, albumin, ALT, and AST.

Conclusions:

Redox imbalance was detected in patients with CHC. Responders had significantly lower levels of MDA than non-responders. Serum MDA may be used as a pretreatment predictor of response to antiviral treatment in patients with CHC.     

Melatonin protects against gentamicin-induced nephrotoxicity in rats

Acute renal failure is a major complication of gentamicin (GEN), which is widely used in the treatment of gram-negative infections. A large body of in vitro and in vivo evidence indicates that reactive oxygen metabolites (or free radicals) are important mediators of gentamicin nephrotoxicity. In this study we investigated the role of free radicals in gentamicin-induced nephrotoxicity and whether melatonin, a potent antioxidant could prevent it. For this purpose female Sprague-Dawley rats were given intraperitoneally either gentamicin sulphate (40 mg/kg), melatonin (10 mg/kg), gentamicin plus melatonin or vehicle (control) twice daily for 14 days. The rats were decapitated on the 15th day and kidneys were removed. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood and malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO) and myeloperoxidase (MPO) activity were determined in the renal tissue. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of BUN and creatinine levels. The significant decrease in GSH and increases in MDA levels, PO and MPO activity indicated that GEN-induced tissue injury was mediated through oxidative reactions. On the other hand simultaneous melatonin administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GEN treatment.     

Melatonin-induced reduction in age-related accumulation of oxidative damage in mice

The ever-increasing understanding of oxygen radical-linked diseases, including the biological process of aging, has stimulated general interest in modulating these biological events. Melatonin has been reported to have antioxidant properties in addition to its known hormonal activities. However, reports on low-level chronic administration with its anti-aging influence are scanty. Hence, the present study was aimed to investigate the influence of low-dose chronic administration (0.10 mg/kg bodyweight/day for 3 months) of melatonin again stage-induced oxidative stress in mice tissues, namely brain, liver, spleen and kidney. Sixteen-month-old mice were supplemented with melatonin (0.10 mg/kg body weight/day) for three months and then autopsied (at the age of19 months) for the biochemical estimation of lipid peroxidation, reduced glutathione (GSH), glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px) and serum phosphatase activity. Results indicate that age-induced augmentation (compared to 6–8-week-old mice)in the level of lipid peroxidation, GSSG and acid phosphatase is significantly (P < 0.001)ameliorated in melatonin-treated mice. Age-induced decline in the level of GSH, GSH-Px and alkaline phosphatase activity is inhibited significantly by the long-term administration of melatonin. The findings indicate that low-dose chronic administration of melatonin acts as a free radical scavenger and anti-aging agent. This revised version was published online in July 2006 with corrections to the Cover Date.     

辅酶Q_(10)对移植心脏再灌注损伤保护的实验研究

本文以大鼠腹腔心脏移植为模型,实验组在心脏移植前注入辅酶Q_(10)(CoQ_(10)),术后测定供心组织:1.实验组超氧化物岐化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px)均高于对照组(P<0.01,P<0.05),过氧化脂质(LPO)明显低于对照组(P<0.01),2.超微结构显示实验组的改变较对照组明显减轻.提示:心脏移植前应用CoQ_(10)可明显降低供心氧自由基产生,同时增强机体内源抗氧化酶活性,保护心肌结构,减轻移植心肌组织的损伤.     

Melatonin protects against ionizing radiation-induced oxidative damage in corpus cavernosum and urinary bladder in rats

The objective of this study was to examine the potential radioprotective properties of pharmacological doses of melatonin on corpus cavernosum and bladder tissues of whole-body irradiated (IR) rats. A total of 32 male Sprague-Dawley rats were exposed to irradiation performed with a LINAC which produced 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anesthesia, each rat received a single whole-body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 and 10 mg/kg, i.p.) and decapitated at 12 hr after exposure to irradiation. Another group of rats was followed for 72 hr after IR, where melatonin injections were repeated once daily. Tissue levels of malondialdehyde (MDA), an index of lipid peroxidation, and glutathione (GSH), a key antioxidant, were estimated in corpus cavernosum and urinary bladder. Tissues were also examined microscopically. The results demonstrate that both 12 and 72 hr following IR, tissue levels of MDA were elevated (P < 0.001), while GSH levels were reduced (P < 0.01) in both tissues. On the other hand, melatonin reversed these changes significantly (P < 0.05-0.01), concomitant with the improvement in histological appearances. Our results show that whole-body irradiation causes oxidative damage in the tissues of the genitourinary system. As melatonin administration reversed oxidative organ injury, as assessed by biochemical and histopathological findings, it is suggested that supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy.     

Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in rats

Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU.     

Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage

The antiulcer effect of melatonin on gastric lesions caused by restraint-cold stress was studied with the intent of determining the mechanism of action of this agent. Melatonin dose-dependently prevented restraint-cold stress-induced gastric damage with around 90% inhibition at a dose of 60 mg/kg BW. When compared with already marketed antiulcer drugs such as ranitidine and omeprazole, melatonin was found to be more effective than ranitidine but less effective than omeprazole in preventing stress ulcer. As stress-induced gastric lesions are mainly caused by oxidative damage because of hydroxyl radicals (*OH), the effect of melatonin in scavenging the.OH generated during stress conditions in vivo as well as in an in vitro model system were studied. The results indicate that melatonin caused an 88% reduction of endogenous *OH during stress in vivo, an observation confirmed in an established in vitro system. Furthermore, a decrease in the activity of gastric peroxidase (GPO) and an increase in the gastric mitochondrial superoxide dismutase (Mn-SOD) activity because of restraint-cold stress was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. Moreover, in separate experiments, cotreatment of rats with melatonin and ranitidine or omeprazole was found to protect against stress ulceration in doses at which either of these alone could not protect the stomach. The findings raise the possibility of melatonin being considered as an effective gastroprotective agent individually or as a cotreatment with either ranitidine and omeprazole.     

Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relationship to disease manifestations and activity

Aim: The present work was undertaken to study the status and contribution of oxidative stress in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. Relationship of the markers of oxidative stress to clinical manifestations, disease activity, damage and medications used were well considered. Methods: Thirty SLE and 30 RA female patients were included in the study and clinical examination and investigations were performed and disease activity was assessed. Markers of oxidative stress, including malondialdehyde (MDA) and antioxidant scavengers with glutathione (GSH) and glutathione peroxidase (GSH Px) were assessed. Results: Level of MDA, GSH and GSH Px were remarkably altered in RA and SLE patients compared to controls. Markers of increased oxidative stress and impaired antioxidant capacity were profound in RA and significantly reflected disease activity in RA and SLE, with special attention to alopecia and lupus nephritis. RA patients receiving methotrexate had significantly altered parameters and the steroid dose in SLE patients correlated with these markers. Conclusion: Oxidative stress was increased and more profound in RA than SLE and could well reflect disease activity, with special attention to SLE patients with alopecia and nephritis. Medications used are closely related to the oxidant/antioxidant imbalance. Considering antioxidants in novel therapeutic strategies is important in SLE and RA patients.     

Melatonin protects against rotenone-induced oxidative stress in a hemiparkinsonian rat model

In the present study, we evaluated the effect of melatonin, a well-known free radical scavenger and neuroprotector, against rotenone-induced oxidative stress in a hemiparkinsonian rat model. The effect of melatonin on glutathione (GSH) depletion caused by unilateral, intranigral infusion of rotenone was investigated employing a spectrofluorimetric procedure. We also studied the effect of melatonin on rotenone-induced changes in the antioxidant enzymes superoxide dismutase (SOD) and catalase in the cytosolic fractions of substantia nigra (SN), employing spectrophotometric procedures. Rotenone-induced hydroxyl radicals (*OH) in the isolated mitochondria, as measured employing a sensitive HPLC-electrochemical method, were significantly scavenged by melatonin. Melatonin treatment restored the rotenone-induced decrease in GSH level and changes in antioxidant enzyme (SOD and catalase) activities in the SN. Our results strongly indicate melatonin's beneficial use in Parkinson's disease therapy as an antioxidant.     

芍药苷通过抑制氧化应激及凋亡保护高糖诱导大鼠皮质神经元损伤

目的探讨芍药苷对高糖诱导大鼠皮质神经元氧化应激及凋亡的保护作用。方法从新生SD乳鼠大脑皮质分离和培养神经元,4 d后分为对照组、高糖组(50 mmol/L高糖)、低、中和高浓度组(2.5、5.0、10.0μmol/L芍药苷预处理再加50 mmol/L高糖)。采用细胞增殖活力检测试剂观察细胞活力,用吸光度(A)值表示;检测超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性;通过2′,7′-二氢二氯荧光素二乙酸酯荧光探针检测活性氧水平;Hoechst 33342染色检测细胞凋亡;免疫荧光染色测定细胞线粒体膜电位(MMP);Western blot测定Bcl-2、Bax、裂解的半胱氨酸天冬氨酸蛋白酶3(cleaved-Caspase3)蛋白表达。结果与对照组比较,高糖组A值明显降低(0.452±0.505 vs 0.985±1.010,P<0.01)。与高糖组比较,低浓度组A值无明显变化(P>0.05),中和高浓度组A值增高(0.648±0.714和0.782±0.805 vs 0.452±0.505,P<0.05,P<0.01);SOD、CAT活性增加,活性氧水平降...