The Roles of Melatonin and Vitamin E Plus Selenium in Prevention of Oxidative Stress Induced by Naloxone-Precipitated Withdrawal in Heroin-Addicted Rats

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.     

Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia

In this article, oxidative stress and enzymic-non-enzymic antioxidants status were investigated in children with acute pneumonia. Our study included 28 children with acute pneumonia and 29 control subjects. The age ranged from 2 to 11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There was a statistically significant difference between the groups for all parameters except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were higher in the study group than those of the control group. However, SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the study group compared with the control group. All antioxidant vitamin activities were decreased in children with acute pneumonia. Our study demonstrated that oxidative stress was increased whereas enzymic and non-enzymic antioxidant activities were significantly decreased in children with acute pneumonia.     

24-hour rhythms in oxidative stress during hepatocarcinogenesis in rats: effect of melatonin or alpha-ketoglutarate

To compare the effects of alpha-ketoglutarate (alpha-KG) and melatonin on 24-h rhythmicity of oxidative stress in N-nitrosodiethylamine (NDEA)-injected Wistar male rats, melatonin (5 mg/kg i.p.) or alpha-KG (2 g/kg through an intragastric tube) was given daily for 20 weeks. In blood collected at 6 time points during a 24-h period, serum activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein (alpha-FP) were measured as markers of liver function. To assess lipid peroxidation and the antioxidant status, plasma levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured, together with the activity of erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). NDEA augmented mesor and amplitude of rhythms in AST and ALT activity and plasma alpha-FP levels and mesor values of plasma TBARS, while decreasing mesor values of plasma GSH and erythrocyte SOD, CAT, GPx and GST. Acrophases were delayed by NDEA in all cases except for alpha-FP rhythm, which became phase-advanced. Co-administration of melatonin or alpha-KG partially counteracted the effects of NDEA. Melatonin decreased mesor of plasma TBARS and augmented mesor of SOD activity. The results indicate that melatonin and alpha-KG are effective in protecting from NDEA-induced perturbation of 24-h rhythms in oxidative stress. Melatonin augmented antioxidant defense in rats.     

Fluoride-Induced Oxidative Stress in Rat’s Brain and Its Amelioration by Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Pineal Proteins and Melatonin

Fluoride (F) becomes toxic at higher doses and induces some adverse effects on various organs, including brain. The mechanisms underlying the neurotoxicity caused by excess fluoride still remain unknown. The aims of this study were to examine F-induced oxidative stress (OS) and role of melatonin (MEL) and buffalo pineal proteins (PP) against possible F-induced OS in brain of rats. The 24 rats were taken in present study and were divided into four groups: control, F, F + PP, and F + MEL. The F group was given 150 mg/L orally for 28 days. Combined 150 ppm F and 100 μg/kg BW (i.p.) PP and F (150 ppm) + MEL (10 mg/kg BW, i.p.) were also administered. The activities of enzymatic, viz., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), and non-enzymatic, viz., reduced glutathione (GSH) concentration, and the levels of malondialdehyde (MDA) in the brain tissue were measured to assess the OS. Fluoride administration significantly increased brain MDA compared with control group, while GSH levels were decreased in fluoride-treated groups, accompanied by the markedly reduced SOD, GPx, GR, and SOD activity. Buffalo PP and MEL administration caused brain MDA to decrease but caused SOD, GPx, GR, GSH, and CAT activities to increase to significant levels in F-treated animals. Together, our data provide direct evidence that buffalo PP and MEL may protect fluoride-induced OS in brain of rats through mechanisms involving enhancement of enzymatic and non-enzymatic antioxidant defense system. Therefore, this study suggested that PP and MEL can be useful in control of neurotoxicity induced by fluoride.     

Effects of melatonin in reducing the toxic effects of doxorubicin

Anthracycline antibiotics, such as doxorubicin and daunorubicin, constitute a group of wide spectrum therapeutic agents. Application of these drugs in chemotherapy is limited because of their toxic effects. Melatonin, the main secretory product of pineal gland, was recently found as a free radical scavenger and antioxidant.We decided to evaluate the tissue protective effect of melatonin against toxic effects of doxorubicin in six groups of rats. Rats were given doxorubicin (Dx) (45 mg/kg dose), melatonin (MEL) (10 mg/kg), first doxorubicin and then melatonin (DM), first melatonin and then doxorubicin (MD).The degree of kidney, lung, liver and brain cells' alterations were examined biochemically.In doxorubicin-treated group, malondialdehyde (MDA) levels of kidney, lung, liver and brain tissues were significantly increased but glutathione (GSH) levels were decreased compared to control rats. In the group in which first doxorubicin and then melatonin were given, MDA levels were significantly decreased compared to the doxorubicin-treated group.In doxorubicin-treated group, serum levels of creatinine, uric acid, blood urea nitrogen (BUN), Gamma-glutamyl transpeptidase (GGT) and Lactic acid dehydrogenase (LDH) were significantly increased while serum albumin and total protein levels were significantly decreased compared to control rats.Melatonin decreased the intensity of the changes produced by the administration of doxorubicin alone. Melatonin was quite efficient in reducing the formation of lipid peroxidation, restoring the tissue GSH contents and alterations of serum levels.     

The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts

Melatonin plays several important physiological functions in mammals, such as immune enhancement and regulation of dark-light signal transduction. Melatonin is also known to be an endogenous free radical scavenger and an efficient antioxidant. It detoxifies a variety of free radicals and reactive oxygen intermediates, including the hydroxyl radical, singlet oxygen and nitric oxide. These radicals participate in many diseases, for example diabetes. This study determined the effect of melatonin on the antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and the level of glutathione (GSH) in human diabetic (C2 line) skin fibroblasts. Confluent monolayers of control (S2 line) and diabetic (C2 line) skin fibroblasts were incubated with different concentrations of melatonin: 10, 50, 100 and 1000 micromol/l at 37 degrees C for 24 h. Next, the GSH level and SOD, CAT and GPx activities were measured colorimetrically. The activities of the antioxidant enzymes and the GSH level were lower in diabetic skin fibroblasts than in the control S2 line. Concentrations of melatonin of 100 and 1000 micromol/l caused a significant increase in the enzymes' activities and GSH level.     

Lead-induced oxidative damage in rats/mice: A meta-analysis

BackgroundLead (Pb) is ubiquitous in the environment and is an environmental genotoxic metal. Pb accumulation in the body could cause the oxidative stress.ObjectiveThis meta-analysis aimed to perform a systematic evaluation of the extent of oxidative damage in rats/mice induced by lead.MethodsAll relevant articles in English or Chinese were retrieved from Embase, PubMed, Web of Science, Medline, China National Knowledge Infrastructure, and Chinese Biological Medicine databases from their inception date until July 22, 2018.ResultsA total of 108 eligible articles were included in this study. The indicators of oxidative stress included malondialdehyde (MDA), glutathione disulfide (GSSG), reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione-s-transferase (GST). The meta-analysis showed that lead significantly increased oxidants levels, such as MDA, GSSG, ROS, and H₂O₂ (P < 0.05), and significantly reduced the level of antioxidants, such as CAT, GPx, GR, GSH, SOD, and GST (P < 0.05). The intraperitoneal mode was more effective than water drinking mode in reducing the levels of CAT, GPx, GSH, and SOD (P < 0.05). Other factors that influenced the overall oxidative stress, including species of animals, type of tissues, and intervention dosage and time, were comprehensively evaluated.ConclusionThe results of meta-analysis indicated that mice were more sensitive to lead than rats, and intraperitoneal mode was an effective intervention mean. High doses and long periods of lead treatment can cause serious oxidative damage. Moreover, testicular was more vulnerable to lead than other tissues. These results provided scientific evidence for preventing and treating lead toxicity.     

Coadministration of melatonin and estradiol in rats: effects on oxidant status.

This study was designed to investigate the effects of melatonin and estradiol (E2) on lipid peroxidation and antioxidant defense enzymes in blood and liver tissue when administered in vivo. Wistar albino rats were divided into three experimental groups and treated with either estradiol (25 mg/kg bw, s.c.), melatonin (i. p.), or melatonin plus E2, whereas control animals had diluent injections only. Melatonin was given 10 mg/kg bw x 2 intraperitoneally 30 min before and 60 min after E2 treatment to the melatonin plus E2 group. Animals were sacrificed three hours after the estradiol injection, and their blood and liver tissues were prepared for biochemical analyses. Tissue malondialdehyde (MDA) levels and antioxidant enzyme activities--superoxide dismutase (SOD) and glutathione peroxidase (GPx)--were determined in the postmitochondrial fraction, and the results were compared. Estradiol injection caused significant increases in both MDA levels and GPx activity in liver. When melatonin was administered in combination with E2, the effect of estradiol on MDA levels was abolished. A significant decrement in SOD activity occurred in melatonin-treated animals. GPx activity in the blood of E2 plus melatonin-injected animals was significantly higher than those in control animals. Melatonin-treated animals exhibited relatively lower levels of SOD activity than those from the control and E2 plus melatonin groups. This indicates that estradiol could exert oxidant action resulting in an increment in tissue malondialdehyde levels. Enhanced activity of GPx in both liver and blood following melatonin injection may indicate the contribution of this neurohormone on the antioxidant defense.     

Melatonin prevents oxidant damage in various tissues of rats with hyperthyroidism

Impairment of thyroid functions brings about pathological changes in different organs of body. Findings of in vivo and in vitro studies indicate that thyroid hormones have a considerable impact on oxidative stress. Melatonin reduces oxidative damage through its free radical eliminating and direct anti-oxidant effects. The present study was undertaken to determine how a 3-week period of intraperitoneal melatonin administration affected oxidative damage caused in experimental hyperthyroidism in rat. The experimental animals were divided into 3 groups (control, hyperthyroidism, hyperthyroidism+melatonin). Malondialdehyde (MDA) and glutathione (GSH) levels were determined in different tissues. MDA levels in cerebral, liver and cardiac tissues in hyperthyroidism group were significantly higher than those in control and hyperthyroidism+melatonin supplemented groups (p<0.001). The highest GSH levels were observed in the group that was administered melatonin in addition to having hyperthyroidism (p<0.001). These results show that hyperthyroidism increased oxidative damage in cerebral, hepatic and cardiac tissues of rat. Melatonin supplementation may also suppress oxidative damage.     

Antioxidant effect of red mould rice in hypercholesterolemic Wistar male rats

The effect of Monascus purpureus red mould rice (RMR) on modulation of lipid metabolism and oxidative stress was studied in hypercholesterolemic rats. Cholesterol feeding for 14 weeks caused a significant increase in the lipid peroxides and total thiols and antioxidant enzymes, viz. glutathione peroxidase (GPx), glutathione reductase (GRd), superoxide dismutase (SOD) and catalase (CAT) in serum and liver in comparison to the control group. However, supplementation of RMR to hypercholesterolemic rats at 8, 12 and 16% significantly increased the GRd, GPx, SOD and CAT activities in serum and liver tissues. Furthermore, RMR feeding significantly decreased total thiols and lipid peroxides and also increased other antioxidant molecules such as glutathione and ascorbic acid in high-cholesterol fed rats. The efficiency of RMR (16%) in modulating the antioxidant molecules and antioxidant enzymes is comparable to standard drug-lovastatin. Thus, this study suggests that the long-term administration of RMR may play an important role in suppressing oxidative stress and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.     

Melatonin concentrations in relation to oxidative status and oocyte dynamics in the ovary during different reproductive phases of an annual cycle in carp Catla catla

The present study on carp Catla catla is the first attempt to search for a relationship between the concentrations of melatonin, oxidative status, and oocyte dynamics in the ovary of any fish. We measured the levels of melatonin, different antioxidative agents, and the marker of intracellular stress along with the profiles of different developmental stages of oocyte in the ovary of adult carp during four distinct phases in an annual reproductive cycle. Ovarian melatonin titers displayed significant seasonal variations with a peak during spawning and nadir during post-spawning, and thereby underlined its proximity to the course of ovarian development. A significant positive correlation was found between the ovarian levels of melatonin and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione transferase (GST), although each of them showed a negative correlation with the level of malondialdehyde (MDA)—a faithful indicator of intracellular stress. However, ovarian melatonin titers did not exhibit any correlation with the levels of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx). Collectively, our findings suggest that melatonin measured in carp ovary may be associated with an enhanced activity/level of selective antioxidative agents for reduction in oxidative stress to augment ovarian functions during the spawning.     

Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney

Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by ochratoxin A (OTA) administration in rats was investigated. Four groups of 15 rats each were used: controls, MEL-treated rats (5 mg/kg body mass), OTA-treated rats (250 μg/kg) and MEL+OTA-treated rats. After 4 weeks of treatment, the levels of malondialdehyde (MDA), a lipid peroxidation product (LPO) were measured in serum and homogenates of liver and kidney. Also, the levels of glutathione (GSH), and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL+OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis.     

Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease

Identifying patients at risk of developing premature coronary artery disease (PCAD) which occurs at age below 45 years old and constitutes approximately 7–10% of coronary artery disease (CAD) worldwide remains a problem. Oxidative stress has been proposed as a crucial step in the early development of PCAD. This study was conducted to determine the oxidative status of PCAD in comparison to CAD patients. PCAD (<45 years old) and CAD (>60 years old) patients were recruited with age-matched controls (n?=?30, each group). DNA damage score, plasma malondialdehyde (MDA) and protein carbonyl content were measured for oxidative damage markers. Antioxidants such as erythrocyte glutathione (GSH), oxidised glutathione (GSSG), and glutathione peroxidase activity (GPx), superoxide dismutase (SOD) and catalase (CAT) were also determined. DNA damage score and protein carbonyl content were significantly higher in both PCAD and CAD when compared to age-matched controls while MDA level was increased only in PCAD (p<.05). In contrast, GSH, GSH/GSSG ratio, α-tocotrienol isomer, and GPx activity were significantly decreased, but only in PCAD when compared to age-matched controls. The decrease in GSH was associated with PCAD (OR?=?0.569 95%CI [0.375???0.864], p?=?.008) and cut-off values of 6.69?μM with areas under the ROC curves (AUROC) 95%CI: 0.88 [0.80–0.96] (sensitivity of 83.3%; specificity of 80%). However, there were no significant differences in SOD and CAT activities in all groups. A higher level of oxidative stress indicated by elevated MDA levels and low levels of GSH, α-tocotrienol and GPx activity in patients below 45 years old may play a role in the development of PCAD and has potential as biomarkers for PCAD.     

The association between oxidative stress and obstructive lung impairment in patients with COPD

An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by body plethysmography. Moderate COPD (FEV1 50-80%) was present in 23, and severe COPD (FEV1 < 50%) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1+/-1.5 vs. 47.7+/-2.9 U/gHb, p<0.05, MDA: 2.4+/-0.1 vs. 2.1+/-0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD.     

Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats

Nasturtium officinale R. Br. (Brassicaceae) has been used as a home remedy by the people of south eastern (SE) region of Iran as a medicinal plant. This therapeutical application has been attributed to Nasturtium officinale (N. officinale) antioxidant capacity which is mostly tested by means of cell-free assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). In addition, the antioxidant effect of N. officinale extract has been investigated in hypercholesterolaemic rats in vivo. The results revealed that the extract has notable scavenging activity against DPPH radicals as well as potent reducing power in FRAP assay. Intragastric administration of N. officinale (500 mg/kg body weight per day) to groups of hypercholesterolaemic rats for 30 days lowered their blood total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively. However, the blood high density lipoprotein cholesterol (HDL-C) levels in the same treated rats increased by 16%. To evaluate the mechanism(s) of action, we studied the antioxidative potential of N. officinale extract in terms of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and also the level of reduced glutathione (GSH) in the liver tissues. In addition, hepatic tissue malondialdehyde level (MDA, an index of lipid peroxidation) was also determined. Under hypercholesterolaemic condition, hepatic MDA was increased. Moreover, our data indicated GSH depletion along with significant reduction in the activities of CAT and SOD in rats fed high-fat diet rats. On the other hand, significant elevation in the activities of GPx and GR were seen in the same group of rats. Treatment of hypercholesterolaemic rats with N. officinale extract significantly increased the GSH level along with enhanced CAT and SOD activities in liver tissues. Furthermore, N. officinale extract significantly decreased hepatic MDA as well as GPx and GR activities in plant-treated rats. Based on our data, it can be concluded that N. officinale has a high hypolipidaemic activity and this may be attributed to its antioxidative potential.     

The effect of melatonin on lipid peroxidation and nitrite/nitrate levels, and on superoxide dismutase and catalase activities in kainic acid-induced injury

Kainic acid (KA) initiates neuronal injury and death by inducing oxidative stress and nitric oxide release from various regions of the brain. It was recently shown that melatonin has free radical-scavenging action and may protect against kainate-induced toxicity. In order to assess the possible supportive effect of melatonin treatment in KA-induced injury in the rat brain cortex, we determined malondialdehyde (MDA) levels as an index of lipid peroxidation, and assessed the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of nitrite/nitrate 35 male rats were divided into five groups, each receiving a different intraperitoneal treatment: saline solution (0.2 ml), kainic acid (15 mg/kg), melatonin (20 mg/kg), KA then melatonin (each as above, 15 min apart), or melatonin then KA (each as above, 30 min apart). Administration of KA caused an about five-fold increase in the catalase activity and an increase in the SOD activity in the cortex relative to the activities for the controls. Treatment with melatonin 15 min after KA injection kept malondialdehyde levels and catalase and superoxide dismutase activities at the normal levels, and led to an increase in the levels of nitrite/nitrate. Our data suggests that melatonin treatment following KA administration has a protective effect on antioxidant enzyme activities and thus supports the role of melatonin and oxidative stress in the regulation of antioxidative enzyme activity.     

Ameliorative action of melatonin on oxidative damage induced by atrazine toxicity in rat erythrocytes

Excessive generation of reactive oxygen species (ROS) can induce oxidative damage to vital cellular molecules and structures including DNA, lipids, proteins, and membranes. Recently, melatonin has attracted attention because of their free radical scavenging and antioxidant properties. The aim of this study was to evaluate the possible protective role of melatonin against atrazine-induced oxidative stress in rat erythrocytes in vivo. Adult male albino rats of Wistar strain were randomly divided into four groups. Control group received isotonic saline; melatonin (10 mg/kg bw/day) group; atrazine (300 mg/kg of bw/day) group; atrazine + melatonin group. Oral administration of atrazine and melatonin was given daily for 21 days. Oxidative stress was assessed by determining the glutathione (GSH) and malondialdehyde (MDA) level, and alteration in antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G-6-PD) in the erythrocytes of normal and experimental animals. A significant increase in the MDA levels and decrease in the GSH was observed in the atrazine treated animals (P < 0.05). Also, significant increase in the activities of SOD, CAT, GPx, and GST were observed in atrazine treated group compared to controls (P < 0.05). Moreover, significant decrease in protein, total lipids, cholesterol, and phospholipid content in erythrocyte membrane were demonstrated in atrazine treated rats. Administration of atrazine significantly inhibits the activities of G-6-PD and membrane ATPases such as Na(+)/K(+)-ATPase, Mg(2+)-ATPase, and Ca(2+)-ATPase (P < 0.05). Scanning electron microscopic (SEM) examination of erythrocytes revealed morphological alterations in the erythrocytes of atrazine treated rats. Furthermore, supplementation of melatonin significantly modulates the atrazine-induced changes in LPO level, total lipids, total ATPases, GSH, and antioxidant enzymes in erythrocytes. In conclusion, the increase in oxidative stress markers and the concomitant alterations in antioxidant defense system indicate the role of oxidative stress in erythrocytes of atrazine-induced damage. Moreover, melatonin shows a protective role against atrazine-induced oxidative damage in rat erythrocytes.     

Creatine prevents the imbalance of redox homeostasis caused by homocysteine in skeletal muscle of rats

Homocystinuria is a neurometabolic disease caused by severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction, being that the pathomechanism is not fully understood. In the present study we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely 2′7′dichlorofluorescein (DCFH) oxidation, levels of thiobarbituric acid-reactive substances (TBARS), antioxidant enzyme activities (SOD, CAT and GPx), reduced glutathione (GSH), total sulfhydryl and carbonyl content, as well as nitrite levels in soleus skeletal muscle of young rats subjected to model of severe hyperhomocysteinemia. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3–0.6 μmol/g body weight), and/or creatine (50 mg/kg body weight) from their 6th to the 28th days age. Controls and treated rats were decapitated at 12 h after the last injection. Chronic homocysteine administration increased 2′7′dichlorofluorescein (DCFH) oxidation, an index of production of reactive species and TBARS levels, an index of lipoperoxidation. Antioxidant enzyme activities, such as SOD and CAT were also increased, but GPx activity was not altered. The content of GSH, sulfhydril and carbonyl were decreased, as well as levels of nitrite. Creatine concurrent administration prevented some homocysteine effects probably by its antioxidant properties. Our data suggest that the oxidative insult elicited by chronic hyperhomocystenemia may provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function. Creatine prevents some alterations caused by homocysteine.     

The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid.

The antiulcerogenic effect of diffractaic acid (DA) isolated from Usnea longissima, a lichen species, on indomethacin (IND)-induced gastric lesions was investigated in rats. Administration of 25, 50, 100 and 200 mg/kg doses of DA and ranitidine (RAN) (50 mg/kg dose) reduced the gastric lesions by 43.5%, 52.9%, 91.4%, 96.7% and 72.7%, respectively. It is known that oxidative stress leads to tissue injury in organisms. Thus, in all treated groups of rats, the in vivo activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were evaluated. IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats. In contrast to IND, the administration of DA and RAN showed a significant decrease in LPO level and an increase in tissue SOD, GPx and GSH levels. However, while CAT activity was significantly increased by the administration of IND, the administration of DA and RAN decreased CAT activity. The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues. In contrast to IND, the administration of DA and RAN decreased MPx activity. The changes in activities of gastric mucosal nitric oxide synthases (NOS) throughout the development of gastric mucosal damage induced by IND were also studied. A decrease in constitutive NOS (cNOS) activity and an increase in inducible NOS (iNOS) activity were determined in gastric damaged tissues induced by IND. The administration of DA (100 mg/kg dose) and RAN reversed the activities of iNOS and cNOS. These results suggest that the gastroprotective effect of DA can be attributed to its enhancing effects on antioxidant defense systems as well as reducing effects of neutrophil infiltration.     

Melatonin supplementation improves oxidative and inflammatory state in the blood of professional athletes during the preparatory period for competitions

Melatonin supplementation has been proved to have antioxidant and anti-inflammatory effects in humans. The aim of the study was to estimate the influence of a 30-day melatonin supplementation on oxidative and inflammatory state in the blood of intense training professional athletes. The study was conducted in 47 football players, 19 rowers, and 15 adults who did not practice sports (control group). Blood samples were taken once from the control group and twice from the athletes: before and after 30-day melatonin administration (5?mg daily before sleep). Serum levels of melatonin, isoprostanes, antiox-LDL antibodies, interleukin-6, and C-reactive protein were measured. In erythrocytes, the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), and the activities of glutathione peroxidase (GSH-Px), cytoplasmic superoxide dismutase (SOD-1), and glutathione reductase (GR) were determined. Melatonin supplementation caused a significant decrease in markers of oxidative stress and a significant increase in melatonin concentration and the activities of SOD-1 and GSH-Px in athletes. The obtained data showed increased oxidative stress and inflammatory processes in professional athletes during intense training and indicated that supplementation of melatonin in their daily diet may have a beneficial effect on the protection of tissues against the adverse action of RONS and inflammatory processes.