Dantrolene protects erythrocytes against oxidative stress during whole-body irradiation in rats

In our study, we examined the radioprotective effects of dantrolene against gamma irradiation-induced damage of blood cells after total body irradiation of rats. Rats were divided into three groups of eight rats each. The first group was the control group receiving no dantrolene or irradiation, the second group received total body irradiation (RT) with 5 Gy of gamma irradiation only, and the third group received dantrolene at a dose of 5 mg x kg(-1) plus RT. Dantrolene was given intraperitoneally 30 min before RT. All groups were sacrificed 2 h after RT, and blood samples were taken. Leukocyte, and thrombocyte counts and hemoglobin levels were measured. Furthermore, malondialdehyde (MDA) levels in plasma and erythrocytes and superoxide dismutase (SOD) and glutathione peroxidase activities (GSH-Px) in erythrocytes were determined. It was found that pretreatment with dantrolene at a dose of 5 mg x kg(-1) significantly reduced the MDA levels and increased the antioxidant SOD and GSH-Px activities, and prevented the decrease in leukocyte and thrombocyte counts. We conclude that dantrolene has clear antioxidant properties when given prior to radiation exposure and the protective effect of dantrolene against damage inflicted by radiation, depends, at least in part, on the decrease in lipid peroxidation and increase in the activity of antioxidant enzymes SOD and GSH-Px.     

Melatonin attenuates methotrexate‐induced oxidative stress and renal damage in rats

Nephrotoxicity is an adverse side effect of methotrexate (MTX) chemotherapy. The present study verifies whether melatonin, an endogenous antioxidant prevents MTX‐induced renal damage. Adult rats were administered 7 mg/kg body weight MTX intraperitoneally for 3 days. In the melatonin pretreated rats, 40 mg/ kg body weight melatonin was administered daily intraperitoneally 1 h before the administration of MTX. The rats were killed 12 h after the final dose of MTX/vehicle. The kidneys were used for light microscopic and biochemical studies. The markers of oxidative stress were measured along with the activities of the antioxidant enzymes and myeloperoxidase activity in the kidney homogenates. Pretreatment with melatonin reduced MTX induced renal damage both histologically and biochemically as revealed by normal plasma creatinine levels. Melatonin pretreatment reduced MTX induced oxidative stress, alteration in the activity of antioxidant enzymes as well as elevation in myeloperoxidase activity. The results suggest that melatonin has the potential to reduce MTX induced oxidative stress, neutrophil infiltration as well as renal damage. As melatonin is an endogenous antioxidant and is non‐toxic even in high doses it is suggested that melatonin may be beneficial in minimizing MTX induced renal damage in humans. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

The effect of melatonin on eye lens of rats exposed to ultraviolet radiation

We investigated the influence of exogenously administered melatonin on adult rats eye lenses exposed to ultraviolet radiation (UV) A and B ranging from 356-254 nm irradiation at 8 microW/cm(2). Rats exposed to this range of UV for 15 min for one week showed a significant (P<0.05) reduction in antioxidant enzymes activities; superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and elevated (P<0.001) lipid peroxidation served as an index of cellular damage by free radicals. UV-radiation significantly (P<0.001) elevated calcium ions (Ca(2+)) and lactate dehydrogenase (LDH) activity in lenses. Depleting animals of their stores of important intracellular antioxidant and elevating lenticular Ca(2+) by UV irradiation, may be the main cause of lens opacification. Melatonin injection with radiation significantly reduced (P<0.05) lipid peroxidation, Ca(2+) and (P<0.001) for LDH. When melatonin was injected after radiation, SOD and GSH-Px enzyme activities increased significantly (P<0.01), and lipid peroxidation, Ca(2+) levels and LDH activities were reduced significantly. Melatonin injection after UV radiation was as effective as melatonin treatment concurrent with UV irradiation. We conclude that melatonin may protect the eye lens from the damaging effects of UV exposure, and its actions protect lens from oxidative stress, elevating Ca(2+) levels, which are considered as an important causes of cataractogenesis.     

Protective effects of melatonin and caffeic acid phenethyl ester against retinal oxidative stress in long-term use of mobile phone: A comparative study

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the efficacy of the protective effects of melatonin and CAPE against retinal oxidative stress due to long-term exposure to 900 MHz EMR emitting mobile phones. Melatonin and CAPE were administered daily for 60 days to the rats prior to their EMR exposure during our study. Nitric oxide (NO, an oxidant product) levels and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of retinal oxidative stress in rats following to use of EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in retinal tissue. Retinal levels of NO and MDA increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of NO and MDA. Likewise, retinal SOD, GSH-Px and CAT activities decreased in EMR exposed animals while melatonin and CAPE caused a significant increase in the activities of these antioxidant enzymes. Treatment of EMR exposed rats with melatonin or CAPE increased the activities of SOD, GSH-Px and CAT to higher levels than those of control rats. In conclusion, melatonin and CAPE reduce retinal oxidative stress after long-term exposure to 900 MHz emitting mobile phone. Nevertheless, there was no statistically significant difference between the efficacies of these two antioxidants against to EMR induced oxidative stress in rat retina. The difference was in only GSH-Px activity in rat retina. Melatonin stimulated the retinal GSH-Px activity more efficiently than CAPE did.     

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.     

Melatonin effect on renal oxidative stress under constant light exposure

Recently, numerous studies have shown antioxidant actions of melatonin. Melatonin at both physiological and pharmacological levels stimulates glutathione peroxidase, glutathione reductase and superoxide dismutase activities in the brains of rats and chickens. This study was designed to evaluate the effect of melatonin on nephropathy and oxidative stress under constant light exposure. Nephropathy was induced by adriamycin administered in a single dose (25 mg kg(-1) b.w., i.p.). Melatonin was injected i.p. (1,000 microg kg(-1) b.w./day). Malondialdehyde, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione transferase, catalase and superoxide dismutase were determined in kidney. Urea, creatinine and total proteins in plasma and proteinuria were evaluated and melatonin was determined. Results show a decrease in melatonin levels. Similar effects occurred with the antioxidant enzyme activities and reduced glutathione. Likewise, adriamycin and constant light induced significant enhancement of malondialdehyde. All changes induced both by adriamycin and constant light were reverted to normal by melatonin administration. Constant light exposure was associated with an increase in oxidative stress and nephropathy induced by adriamycin. Treatment with melatonin decreased lipid peroxides, and permitted a recovery of reduced glutathione, scavenger enzyme activity and parameters of renal function.     

Plasma and erythrocytes antioxidant status and trace element levels in proteinuric patients with moderate glomerular function.

The objective of the study was to investigate the effect of moderate glomerular dysfunction on oxidative stress. We determined the plasma and erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte glutathione (GSH) levels and activities of GSH-Px, GSH Red and SOD as an antioxidant enzymes, and plasma trace element levels containing Fe, Cu and Zn in twenty proteinuric patients (6.8 +/- 5.1 g/day) with moderate glomerular function and in 20 anemic control subjects. We found that the erythrocyte and plasma MDA levels and erythrocyte GSH-Px activities were significantly higher (p < 0.001, p < 0.001, p < 0.001, respectively) and the erythrocyte GSH levels and activities of GSH-Red and SOD activities were significantly lower (p < 0.001, p < 0.001, p < 0.001, respectively) in the patients than in the anemic subjects. Plasma Fe and Zn levels were not to be found significantly different in the patients compared to the anemic subjects. But plasma Cu levels were significantly higher in the patients (p < 0.05) when compared with the levels of anemic subjects. This study was concluded that cellular antioxidant activity decreases in proteinuric patients with moderate glomerular function. This may increase lipid peroxidation reactions by causing oxidative stress in erythrocyte membranes.     

Protective effects of melatonin on myocardial ischemia/reperfusion induced infarct size and oxidative changes

Free radicals, calcium overloading and loss of membrane phospholipids play an important role in the development of ischemia/reperfusion (I/R) injury. Melatonin is a well-known antioxidant and free radical scavenger. Melatonin may also reduce the intracellular calcium overloading and inhibit lipid peroxidation. This study was designed to investigate the effects of melatonin on the I/R-induced cardiac infarct size in an in vivo rat model. We also investigated glutathione (GSH) levels, an antioxidant the levels of which are influenced by oxidative stress, and malondialdehyde (MDA) levels, which is an index of lipid peroxidation. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Melatonin (10 mg/kg) or vehicle was given 10 min before ischemia via the jugular vein. Infarct size, expressed as the percentage of the risk zone, was found significantly greater in I/R group than in the melatonin-treated I/R group. MDA levels were significantly higher, but GSH levels were lower in the I/R group than in the control group. Melatonin significantly reduced the MDA values and increased the GSH levels. These results suggest that oxidative stress contributes to myocardial I/R injury and melatonin administration exerts a mitigating effect on infarct size. Furthermore, the results indicated that melatonin improves the antioxidant capacity of the heart and attenuates the degree of lipid peroxidation after I/R.     

Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats

In view of the antioxidant properties of melatonin, the effects of melatonin on the oxidative-antioxidative status of tissues affected by diabetes, e.g. liver, heart and kidneys, were investigated in streptozotocin (STZ)-induced diabetic rats in the present study. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tissues were compared in three 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(-1) 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(-1) i.p. dose of melatonin per day. After 6 weeks, the rats in groups II and III had significantly lower body weights and higher blood glucose levels than the rats in group I (p < 0.001 and p < 0.001, respectively). MDA levels in the liver, kidney and heart of group II rats were higher than that of the control group (p < 0.01, p < 0.05, p < 0.01, respectively) and diabetic rats treated with melatonin (p < 0.05). The GSH, GSH-Px and SOD levels increased in diabetic rats. Treatment with melatonin changed them to near control values. Our results confirm that diabetes increases oxidative stress in many organs such as liver, kidney and heart and indicate the role of melatonin in combating the oxidative stress via its free radical-scavenging and antioxidant properties.     

Effect of melatonin on oxidative status of rat brain, liver and kidney tissues under constant light exposure

An enormous amount of data has been published in recent years demonstrating melatonin's defensive role against toxic free radicals. In the present study, we examined the role of melatonin as an antioxidant against the effect of continuous light exposure. Rats were divided into three groups. Control rats (group A) were kept under natural conditions whereas other group of rats (group B and C) were exposed to constant light for inhibition of melatonin secretion by the pineal gland. Group C rats also received melatonin via s.c. injection (1 mg x kg(- 1) body weight x day(- 1)). At the end of experiment, all animals were sacrificied by decapitation, serum and tissue samples were removed for determination of malondialdehyde (MDA), a product of lipid peroxidation, conjugated dienes levels and glutathione peroxidase (GSH-Px) activity levels. It was found that lipid peroxidation was increased in the rats which were exposed to constant light. Melatonin injection caused a decrease in lipid peroxidation, especially in the brain. In addition, melatonin application resulted in increased GSH-Px activity, which has an antioxidant effect. Thus, melatonin is not only a direct scavenger of toxic radicals, but also stimulates the antioxidative enzyme GSH-Px activity to detoxify hydroxyl radical produced by constant light exposure.     

Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide

This study was designed to evaluate and compare the effect of melatonin, vitamin E and L-carnitine on brain and liver oxidative stress and liver damage. Oxidative stress and hepatic failure were produced by a single dose of thioacetamide (TAA) (150 mg kg(-1)) in Wistar rats. A dose of either melatonin (3 mg kg(-1)) vitamin E (20 mg kg(-1) ) or L-carnitine (100 mg kg(-1)) was used. Blood samples were taken from the neck vasculature in order to determine ammonium, blood urea nitrogen (BUN) and liver enzymes. Lipid peroxidation products, glutathione (GSH) content and antioxidative enzymes were determined in cerebral and hepatic homogenates. The results showed a decrease in BUN and in the antioxidant enzymes activities and GSH in the brain and liver. Likewise, TAA induced significant enhancement of lipid peroxidation products levels in both liver and brain, as well as in ammonia values. Melatonin, vitamin E and L-carnitine, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore melatonin combined with TAA, decreased the ammonia levels and increased the BUN values compared with TAA animals. Also it was more effective than vitamin E or L-carnitine in these actions. These data show the protective effect of these agents, especially melatonin, against oxidative stress and hepatic damage present in fulminant hepatic failure.     

Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum

Free radicals derived from molecular oxygen have been reported to be responsible for changes in motility and mucosal damage observed in intestinal ischemia-reperfusion injury. Melatonin has been considered as an antioxidant that prevents injuries resulted from I/R in various tissues. The present study was designed to determine the effect of melatonin on the contractile responses of acetylcholine (Ach) and KCl, on malondialdehyde (MDA), a product of lipid peroxidation, and reduced glutathione (GSH) levels and to assess histopathological changes in the smooth muscle of terminal ileum subjected to ischemia-reperfusion. The intestinal ischemia-reperfusion was induced by occlusion of superior mesenteric artery of rat for 30 min, followed by a period of reperfusion for 3 h. Melatonin at doses of 10 or 50 mg/kg was administered via the tail vein in 5 min prior to reperfusion. Following reperfusion, segments of terminal ileum were rapidly taken and transferred into isolated organ bath and responses to Ach and KCl were recorded. Samples of terminal ileum were also taken for measuring the MDA and GSH levels. EC50 values of these contracting substances were seriously reduced in the ischemia-reperfusion group compared to that of the sham-operated control group. The decreased contraction response to Ach and KCl was significantly ameliorated by a dosage of 50 mg/kg of melatonin, while not by a dosage of 10 mg/kg. Similar pattern of the effect was observed in the tissue levels of MDA and GSH as well as in histological improvement. Melatonin appeared to be restoring the amounts of tissue MDA and GSH back to about control levels. These results suggest that the high dose of melatonin not only physiologically but also biochemically and morphologically could be useful to normalize contractility injured by oxidative stress in intestinal ischemia-reperfusion.     

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (β) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1β and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated β cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1β and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting β cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.     

The effects of melatonin on glutathione peroxidase activity in serum and erythrocytes after adriamycin in normal and pinealectomised rats

INTRODUCTION: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It has been shown that MEL can scavenge free radicals, both directly and indirectly, stimulating the activity of antioxidative enzymes such as glutathione peroxidase (GSH-Px). THE AIM OF THE STUDY: The aim of the study was to examine the effect of MEL on serum and erythrocyte GSH-Px activity after ADR in normal and pinealectomised rats. MATERIAL AND METHODS: Wistar rats were divided into the three groups: control animals (Intact), sham-operated (Sham-PX) and pinealectomised (Px). Each of the groups was divided into four subgroups, injected with: 1--saline, 2--MEL, 3--ADR and 4--ADR + MEL. ADR was administered 2 months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before and 2 days after ADR. After 6 days of treatment, the rats were killed by decapitation. Their blood was collected for measurements. RESULTS: In serum GSH-Px activity decreased in all the groups after ADR. Pinealectomy decreased the activity of the enzyme in all the groups of animals examined. In erythrocytes GSH-Px decreased after ADR in the Px-animals. The effect of pinealectomy on erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px activity. MEL did not change GSH-Px activity after ADR. CONCLUSION: Melatonin, in pharmacological concentrations, did not influence the activity of GSH-Px, either in normal or in pinealectomised rats after ADR. A deficiency of endogenous melatonin production may inhibit GSH-Px activity.     

Circadian Variation in the Response to Experimental Endotoxemia and Modulatory Effects of Exogenous Melatonin

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5?mg/kg), LPS?+?melatonin (1?mg/kg), or LPS?+?melatonin (10?mg/kg) at either daytime or nighttime. Superoxide dismutase (SOD) was analyzed in liver samples collected after decapitation. Furthermore, inflammatory plasma markers (cytokines interleukin [IL]-6, IL-10) and oxidative plasma markers (ascorbic acid [AA], dehydroascorbic acid [DHA], and malondialdehyde [MDA]) were analyzed before and 5?h after the onset of endotoxemia. There were significant higher levels of SOD (p?<?0.05), IL-6 (p?<?0.01), and IL-10 (p?<?0.05) during nighttime endotoxemia compared with daytime. At daytime, melatonin 1 and 10?mg reduced the levels of MDA and increased SOD, IL-6, IL-10, and DHA (p?<?0.05). At nighttime, melatonin reduced the levels of MDA and increased DHA (p?<?0.05). Additionally, 10?mg melatonin resulted in lower levels of AA during daytime (p?<?0.05). No dose relationship of melatonin was observed. The results showed that the response induced by experimental endotoxemia was dependent on time of day. Melatonin administration modulated the inflammatory and oxidative stress responses induced by endotoxemia and also resulted in higher levels of antioxidants during daytime. The effect of circadian time on the endotoxemia response and possible modulatory effects of melatonin need further investigations in a human endotoxemia model.     

Effects of garlic extract consumption on plasma and erythrocyte antioxidant parameters in atherosclerotic patients

Effects of ingesting garlic extract on plasma and erythrocyte antioxidant parameters of atherosclerotic patients were investigated in this study. Eleven patients with atherosclerosis participated in the study. They ingested a dose of 1 ml/kg body weight of garlic extract daily for 6 months (study period). Before and after this period, fasting blood samples were obtained, and oxidant (malondialdehyde, MDA and xanthine oxidase, XO) and antioxidant (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) parameters were studied in plasma and erythrocytes obtained from the patients. Blood samples obtained from 11 healthy subjects served as the controls. Plasma XO activity and MDA levels were higher, but plasma and erythrocyte GSH-Px activities were lower, in patients with atherosclerosis relative to those of the control group. Our results showed that ingestion of garlic extract leads to significantly lowered plasma and erythrocyte MDA levels in the patients even in the absence of changes in antioxidant enzyme activities. Our results also demonstrated the presence of oxidant stress in blood samples from patients with atherosclerosis, but ingesting garlic extract prevented oxidation reactions by eliminating this oxidant stress. Thus, it is possible that reduced peroxidation processes may play a part in some of the beneficial effects of garlic in atherosclerotic diseases.     

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.     

Insulin, catecholamines, glucose and antioxidant enzymes in oxidative damage during different loads in healthy humans

Exercise, insulin-induced hypoglycemia and oral glucose loads (50 g and 100 g) were used to compare the production of malondialdehyde and the activity of antioxidant enzymes in healthy subjects. Twenty male volunteers participated in the study. Exercise consisted of three consecutive work loads on a bicycle ergometer of graded intensity (1.5, 2.0, and 2.5 W/kg, 6 min each). Hypoglycemia was induced by insulin (Actrapid MC Novo, 0.1 IU/kg, i.v.). Oral administration of 50 g and 100 g of glucose was given to elevate plasma glucose. The activity of superoxide dismutase (SOD) was determined in red blood cells, whereas glutathione peroxidase (GSH-Px) activity was measured in whole blood. The concentration of malondialdehyde (MDA) was determined by HPLC, catecholamines were assessed radioenzymatically and glucose was measured by the glucose-oxidase method. Exercise increased MDA concentrations, GSH-Px and SOD activities as well as plasma noradrenaline and adrenaline levels. Insulin hypoglycemia increased plasma adrenaline levels, but the concentrations of MDA and the activities of GSH-Px and SOD were decreased. Hyperglycemia increased plasma MDA concentrations, but the activities of GSH-Px and SOD were significantly higher after a larger dose of glucose only. Plasma catecholamines were unchanged. These results indicate that the transient increase of plasma catecholamine and insulin concentrations did not induce oxidative damage, while glucose already in the low dose was an important triggering factor for oxidative stress.     

杜仲绿原酸对高脂小鼠血液流变学作用研究

旨以研究杜仲绿原酸对高脂高胆固醇诱导的高血脂模型小鼠血液流变学的影响,以昆明小鼠为实验动物,随机分成5组:阴性对照组,模型对照组和低剂量(25 mg/kg BW)、中剂量(50 mg/kg BW)、高剂量(100 mg/kg BW)杜仲绿原酸组,每组10只.后4组饲以高脂饲粮,同时小鼠灌胃杜仲绿原酸4周,实验结束,分别测定各组小鼠血液流变学参数、血清和肝脏的抗氧化酶活性和脂质过氧化产物MDA含量及其总抗氧化能力和羟自由基清除率.高脂血症小鼠的全血粘度、血浆粘度、红细胞压积、血沉、纤维蛋白原、红细胞刚性指数和聚集指数显著降低(P＜0.05),红细胞变形指数显著提高(P＜0.05),小鼠血清和肝脏SOD、GSH-Px水平、总抗氧化能力和羟自由基清除能力均显著升高(P＜0.05),MDA水平显著降低(P＜0.05).在高脂膳食条件下,杜仲绿原酸能有效提高血液的抗氧化防御功能(包括抗氧化力、抗氧化酶活性)、改变血液流变学参数等,降低血液粘度、红细胞刚性和聚集,增强变形能力,使细胞膜的流动性增高,其中以中剂量效果相对较好.