Effects of melatonin on streptozotocin-induced diabetic liver injury in rats

This study investigated the possible protective effects of melatonin as an antioxidant against streptozotocin (STZ)-induced diabetic liver injury in rats. Wistar rats were divided into four groups: untreated control (UC), melatonin-treated control (MC), untreated diabetic (UD), and melatonin-treated diabetic (MD). Experimental diabetes was induced by a single-dose (60 mg/kg, intraperitoneally (ip)) STZ injection, and melatonin was injected (200 microg/kg/day, ip) for 4 weeks. Upon light and electron microscopic examination, we observed that melatonin improved the morphological and histopathological changes of the liver caused by diabetes. Malondialdehyde levels in the liver homogenates of UD rats were higher than those of controls and were markedly reduced after melatonin treatment. Although no significant difference was observed with respect to antioxidant status, the superoxide dismutase activity tended to be higher in the UD rats than in the treated rats. Our findings showed that melatonin administration partially reduced liver injury in STZ-induced diabetic rats.     

Effects of pinealectomy and exogenous melatonin on rat hearts

The effects of pinealectomy and administration of melatonin, the major secretory product of the pineal gland, which is a direct free radical scavenger and an indirect antioxidant, were studied in rat hearts on the basis of cardiac morphology and biochemical findings. Three groups of Wistar rats were used: one group was the sham-operated control, one group consisted of pinealectomized rats and one group consisted of pinealectomized rats that were treated with melatonin. Serum cholesterol, tissue levels of malondialdehyde (MDA) and reduced glutathione (GSH), and heart weight were determined. Histochemical staining with the Van Gieson, PAS/Alcian blue at pH 2.5 and Masson's trichrome methods were performed in addition to hematoxylin-eosin staining. Levels of serum cholesterol and tissue MDA, and heart weight were increased in pinealectomized rats whereas GSH levels did not change. Melatonin administration reversed these effects. Microscopically, myocardial fibrosis and myxomatous degeneration of cardiac valves were detected in all pinealectomized rats. It can be concluded that pinealectomy of rats causes morphological changes in rat hearts, and short-term application of melatonin does not reverse these changes.     

Augmentation of indices of oxidative damage in life-long melatonin-deficient rats

The chief pineal secretory product, melatonin, is an efficient free radical scavenger and antioxidant. The current study tested whether the life-long reduction of endogenous melatonin levels due to pinealectomy would influence the accumulation of oxidatively damaged products as the animals aged. Rats were either pinealectomized or sham operated when they were 2-months-old. At 25 months of age these animals were killed along with 2-month-old controls. Aging in the pineal-intact animals was associated with increased levels of lipid peroxidation products (malondialdehyde and 4-hydroxyalkenals in the lung, kidney and skin), rises in an oxidatively damaged DNA product (8-hydroxy-deoxyguanosine in liver, kidney and pancreas), and in the levels of protein carbonyls (in the liver). Likewise, advanced age was associated with a significant decrease in membrane fluidity (increased membrane rigidity) of hepatic microsomes in pineal-intact rats. For all of these parameters and in a number of organs, pinealectomy caused further increases in the indices of oxidative damage. Consistent with previous suggestions, the implications of these findings is that aging is associated with the augmented accumulation of oxidatively damaged macromolecules and that these increases are exaggerated when a relative melatonin deficiency is induced by pinealectomy. The findings are consistent with the idea that the accelerated accumulation of oxidatively damaged products after pinealectomy was due to reduction in melatonin since it functions as a free radical scavenger and antioxidant. On the other hand, other pineal secretory products that were reduced as a consequence of pineal removal may have also been responsible for some of the observed changes.     

Insulin-induced oxidative stress in the brain is nitric oxide-dependent

Insulin is known to increase brain nitric oxide (NO) level and to cause oxidative stress but the relationship between these phenomena has not been well elucidated. This study aimed to examine the role of NO in the insulin-NO-oxidative stress axis in the brain. Mice were grouped into four (n = 5) and treated for seven days with 0.2 ml deionized water (control); 10 I.U./kg insulin; 10 I.U./kg insulin + 50 mg/kg L-NAME; and 50 mg/kg L-NAME. The mice were anaesthesized using ketamine + xylazine and sacrificed at the end of the study. Forebrain was immediately harvested from which brain homogenates were prepared in order to determine NO and malondialdehyde (MDA) concentrations as well as glutathione peroxidase (GPx) activity using commercially available kits. Data were processed using IBM SPSS Statistics 20.0. Nitric oxide values were higher in the insulin group (p < 0.05) but not in the insulin+L-NAME (p > 0.05) group when compared with the control. Values of MDA in the insulin and insulin+L-NAME groups were higher (p < 0.05) and the same (p > 0.05), respectively, than those in the control group. The activity of GPx in the insulin group was lower (p < 0.05) than, but that of the insulin+L-NAME was the same (p > 0.05) as in the control group. Insulin increased NO concentration and oxidative stress as indicated by increased MDA concentration and decreased GPx activity in the treated mice. This insulin effect was reversed by L-NAME (a non-specific NO inhibitor). These data suggest that insulin increased oxidative stress in the brain through an NO-dependent process. Insulin treatment may be harmful to the brain.     

Effect of melatonin and pinealectomy on avoidance and exploratory activity in the rat

Melatonin in a daily dose of 50 μg/rat facilitated the extinction of active avoidance reflex and decreased the intertrial activity during extinction. However, it had no effect on learning and intertrial activity during acquisition. Pinealectomy was ineffective on acquisition, extinction and intertrial activity. Melatonin (100 μg/rat) given in 2 consecutive days facilitated the passive avoidance behavior in water deprived animals in two different experimental situations. Fifty μg of melatonin or pinealectomy was without effect on passive avoidance behavior. Neither melatonin nor pinealectomy had any influence on water intake or on exploratory activity.     

次声对雄性大鼠精子质量和睾丸组织抗氧化系统的影响

目的： 观察次声作用对大鼠精子质量的影响,初步探讨次声对雄性生殖系统的作用机制。方法: 成年雄性SD大鼠分别经8Hz、90dB或130dB的次声作用l、7、14、2l d（2 h/d）,取副睾检测其精子计数、畸形率和活动率,取同侧睾丸检测谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）水平。结果: 8Hz、90dB和130dB次声作用组随次声作用时间延长,精子质量下降,MDA水平升高,GSH-Px下降。在同一时点上,130　dB次声作用组的各项指标与90dB组相比,变化更为显著。结论: 次声对睾丸的生物学效应与其作用参数有关,抗氧化系统失衡可能是该效应的发生机制。     

The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver

The reperfusion following liver ischemia results in hepatocyte damage and apoptosis. The aim of this study was to investigate the effects of two antioxidant agents, carnosine and melatonin, in rat liver ischemia-reperfusion injury. Five study groups were formed; I. sham, II. ischemia-reperfusion, III. ischemia-reperfusion+melatonin, IV. ischemia-reperfusion+carnosine, V. ischemia-reperfusion+melatonin+carnosine. Then 250 mg/kg carnosine and 10 mg/kg melatonin were administered intraperitoneally 30 min before ischemia and immediately after the reperfusion. Sinusoidal dilatation, congestion and neutrophil infiltration were observed in the ischemia-reperfusion group while these symptoms were less pronounced in the treatment groups. Alanine aminotransferase, aspartate aminotransferase and myeloperoxidase levels were increased in the ischemia-reperfusion group while they were lowered in the treatment groups. Glutathione level was low in the ischemia-reperfusion group while it tended to increase in the ischemia-reperfusion+carnosine administered and ischemia-reperfusion+carnosine+melatonin administered groups. There was an increase in the number of apoptotic cells in the ischemia-reperfusion group while this number was lowered in the treatment groups. Carnosine was more effective than melatonin in the reversal of structural and biochemical alterations that resulted from ischemia-reperfusion injury. The administration of melatonin and carnosine together yielded better outcomes compared to the sole administration of each agent.     

HIV-1 Tat蛋白对U87细胞活性及氧化应激的影响

目的:研究HAD和非HAD的艾滋病患者不同部位来源的Tat蛋白氨基酸位点变异及其对U87细胞氧化应激的影响。方法:采用BLAST和MEGA6对一例HAD患者(H)和一例非HAD患者(N)的基底节(BG)、脾脏(SPL)共4个部位来源的HIV-1 Tat蛋白进行序列分析,研究其氨基酸位点变异,并将 tat基因...     

Effects of sprint exercise on oxidative stress in skeletal muscle and liver

Although numerous studies have tested the effects of continuous exercise regimens on antioxidant defences, information on the effect of sprint exercise on the antioxidant defence system and lipid peroxidation levels of tissues is scant. The present study was designed to determine the effects of sprint exercise on the lipid peroxidation and antioxidant enzyme system in liver and skeletal muscle during the post-exercise recovery period in untrained mice. Mice performed 15 bouts of exercise, each comprising running on a treadmill for 30 s at 35 m·min^–1 and a 5° slope, with a 10-s rest interval between bouts. They were then killed by cervical dislocation either immediately (0 h), 0.5 h, 3 h or 24 h after completion of the exercise. Their gastrocnemius muscle and liver tissues were quickly removed. It was found that blood lactate levels increased immediately after the exercise, but had returned to control levels by 0.5 h post-exercise. This exercise regimen had no effect on the activity of superoxide dismutase and glutathione peroxidase in these tissues. Levels of muscle thiobarbituric acid reactive substances (TBARS) had increased at 0.5 and 3 h post-exercise, and then returned to control levels by 24 h post-exercise. In conclusion, acute sprint exercise in mice resulted in an increase in TBARS levels in skeletal muscle; no change was observed in the liver. Antioxidant enzyme activities remained unaffected by acute sprint exercise in these tissues. Electronic Publication     

灯盏花素对糖尿病大鼠肝、肾组织氧化应激的影响

目的：探讨灯盏花素对糖尿病大鼠肝、肾组织氧化应激的影响。方法： 建立STZ诱导的糖尿病模型，随机分3组：正常对照组、模型组、灯盏花素给药组。8周后应用HE、油红O染色对肝组织、PAS染色对肾组织作病理检查。分光光度法检测肝、肾组织丙二醛(MDA)含量及抗氧化物酶活性。结果： HE染色显示模型组部分肝细胞脂肪变性，评分为1.54±0.65，灯盏花素给药组评分为0.55±0.43，差异高度显著(P<0.01)。油红O染色模型组肝组织评分为2.11±0.82，灯盏花素给药组为0.75±0.66，差异高度显著(P<0.01)。模型组大鼠肾重、肾重/体重、24 h尿白蛋白排泄率(AER)与肾小球面积(AG)、肾小球容量(VG) 及系膜区面积(AM)均明显增加，灯盏花素给药组这些改变减轻。灯盏花素给药组肝、肾组织MDA含量明显低于模型组(P<0.05，P<0.01)。超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及谷胱甘肽过氧化物酶(GSH-Px)活性明显高于模型组(P<0.05，P<0.01)。结论： 灯盏花素对糖尿病大鼠肝、肾组织有明显保护作用，其机制部分可能与抑制肝、肾组织氧化应激增加有关。     

乌司他丁对心肺复苏后兔脑组织氧化应激损伤的影响

目的: 观察乌司他丁(ulinastatin,UTI)对心肺复苏(cardiopulmonary resuscitation, CPR)后新西兰兔脑组织氧化应激损伤的影响。方法: (1)建立新西兰兔心脏停搏(cardiac arrest,CA)模型,自主循环恢复(return of spontaneous circulation,ROSC)后24 h内连续采血监测血浆丙二醛(malondialdehyde, MDA)和还原型谷胱甘肽 (glutathione, GSH)的水平;(2) 48只新西兰兔建立CA模型,ROSC后随机分为模型组(model组)和UTI治疗组,观察UTI对大脑皮层和海马内MDA、GSH含量和神经元凋亡的影响,观察UTI对大脑皮层核因子E2 相关因子2(nuclear factor E2-related factor 2, Nrf2)表达的影响。结果: ROSC后2 h 血浆MDA达高峰,GSH降低到较低水平;UTI显著抑制ROSC后大脑皮层和海马MDA水平的升高,提高GSH含量。UTI促进了ROSC后脑组织Nrf2的表达。Model组大脑皮层及海马CA1~CA3区的凋亡神经元数明显多于UTI组。结论: UTI可升高ROSC后兔脑组织GSH水平,降低MDA含量,增加Nrf2的表达,减少神经元的凋亡。     

Low dose of melatonin ameliorates cryptorchidism-induced spermatotoxicity in rats

Introduction

Cryptorchidism has been associated with spermatotoxicity and oxidative stress while melatonin is a well-known anti-oxidant. This study investigated the possible ameliorative effect of melatonin on cryptorchidism-induced spermatotoxicity and oxidative stress.

赛庚啶对内毒素血症小鼠氧化损伤的对抗作用

目的:研究赛庚啶对内毒素(LPS)血症小鼠氧化损伤的对抗作用。方法:小鼠尾静脉注射LPS,造成内毒素血症模型,观察赛庚啶能否提高小鼠24h存活率,并测定血浆NO的水平,心、肝、肾和脑组织中SOD和GSH-Px活力以及脂质过氧化产物MDA含量。结果:赛庚啶预防给药能够显著提高致死量LPS攻击后小鼠24h的存活率,使血浆NO2-/NO3-的水平显著降低,其中高剂量组SOD和GSH-Px活力增高,MDA含量降低。低剂量组SOD活力增高,但肝和脑组织中MDA含量下降不明显,肝和肾组织GSH-Px活力无明显增高。结论:赛庚啶预防给药能够防治LPS血症,改善小鼠LPS血症时重要脏器氧化性损伤状态,抑制血浆NO水平过度升高。     

糖尿病大鼠阴茎的氧化应激与阴茎勃起功能障碍的关系

目的 探讨氧化应激在糖尿病性阴茎勃起功能障碍（ED）中的作用。 方法 注射链脲佐菌素建立糖尿病大鼠模型,分别在注射8周和12周后观察阴茎勃起次数;取大鼠阴茎,测定阴茎丙二醛水平、总抗氧化能力,免疫印迹法检测阴茎核因子E2相关因子2(Nrf2)蛋白量的变化。 结果 糖尿病大鼠的阴茎勃起次数明显低于对照组,并随病程延长降低;糖尿病大鼠阴茎丙二醛水平明显高于对照组,总抗氧化能力水平明显低于对照组;与对照组比较,糖尿病组大鼠阴茎内Nrf2蛋白量随病程延长而降低。 结论 糖尿病性阴茎勃起功能障碍与阴茎氧化应激水平升高相关。     

结肠炎大鼠结肠免疫功能的改变和褪黑素调节

目的:研究褪黑素(MT)对免疫性结肠炎大鼠结肠局部免疫功能的影响。方法:利用三硝基苯磺酸和乙醇复制大鼠免疫性结肠炎模型,设正常对照组、模型对照组、5-氨基水杨酸给药组(5-ASA,100mg·kg~(-1))和MT给药组(2.5,5.0,10.0mg·kg~(-1)),每天灌肠给药1次,从复制模型7d后开始至实验结束共21d。检测大鼠结肠组织白细胞介素(IL-1、IL-2)、肿瘤坏死因子(TNF-α)、一氧化氮(NO)、髓过氧化物酶(MPO)和丙二醛(MDA)水平;另制备模型对照组大鼠炎症结肠匀浆并加入脂多糖LPS,设阴性对照组、模型对照组、5-ASA给药组(终浓度为100μmol/L)和MT给药组(终浓度为0.01,0.1,1.0mmol/L)。取上清测IL-1、IL-2、TNF-α、NO、乳酸脱氢酶(LDH)、MPO和MDA水平。结果:模型对照组大鼠结肠中IL-1、IL-2、TNF-α、NO、MPO和MDA含量增多,MT可呈不同程度的抑制作用;模型对照组大鼠炎症结肠匀浆中IL-1、IL-2、TNF-α、NO、LDH、MPO和MDA含量显著增加,预先加入MT可明显降低IL-1、TNF-α、LDH、MPO和MDA含量,1.0mmol/LMT可明显抑制NO产生。结论:三硝基苯磺酸引起的结肠炎大鼠结肠存在明显免疫功能紊乱,MT可从不同水平调节结肠异常免疫功能减轻大鼠结肠炎症状。     

Catechin protects against oxidative stress and inflammatory-mediated cardiotoxicity in adriamycin-treated rats

Catechin has anti-inflammatory and antioxidative effects. Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the adriamycin use in the treatment of malignant tumors. Thus, the present study aimed to assess the antioxidant and anti-inflammatory effects of catechin on adriamycin-induced cardiotoxicity in rats. Forty-five rats were allocated to three groups: control group, adriamycin group and adriamycin?+?catechin group. We performed the following measurements: lipid peroxidation (MDA), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities as well as, the expression of inflammatory cytokines genes namely nuclear factor kappa-B, tumor necrosis factor and inducible nitric oxide synthase. Catechin administration significantly decreased MDA level and significantly increased CAT, GSH-Px and SOD activities. Also, catechin significantly decreased the expression levels of inflammatory cytokines. Catechin provided cardioprotection on adriamycin-induced cardiotoxicity through their antioxidant and anti-inflammatory properties.     

大鼠自体原位肝移植模型中肠道羟自由基、丙二醛和总抗氧化能力的变化

目的: 建立SD大鼠自体原位肝移植模型,观察自体模拟肝移植后不同时期肠道黏膜病理学变化及肠组织的羟自由基(·OH)、丙二醛(MDA)和总抗氧化能力(T-AOC)的变化。方法: SD大鼠36只,随机分为假手术组(S组)和模型组(M组),模型组根据肝脏再灌注时间,再分为再灌注2 h模型组(M1组)、再灌注4 h模型组(M2组)、再灌注8 h模型组(M3组)、再灌注16 h模型组(M4组)和再灌注24 h模型组(M5组)5个亚组。对照组在麻醉后只进行开腹和血管的分离,不进行肝脏的阻断和灌注;模型组则进行自体肝移植手术。分别在肝脏再灌注后2、4、8、16、24 h取肠组织,观察其病理形态学变化及·OH、MDA和T-AOC的变化。结果: (1)与S组相比,M组大鼠肠黏膜在肝脏再灌注后出现明显的病理学损伤,可见上皮下间隙的扩大,甚至出现绒毛上皮和固有层分离,再灌注8 h时最为显著,再灌注24 h开始修复;(2)与S组相比,M2、M3和M4组·OH水平明显升高(P<0.05),M1、M2、M3组MDA含量明显升高(P<0.05),M1、M2、M3和M4组T-AOC明显降低(P<0.05)。结论: 自体原位肝移植可使大鼠肠黏膜·OH和MDA含量增加,T-AOC下降,肠道出现可逆性病理损伤。     

The antioxidant melatonin reduces cortical neuronal death after intrastriatal injection of kainate in the rat

 The anti-excitotoxic efficacy of the pineal hormone melatonin was investigated in kainate-injured brains of rats. Kainate (a glutamate-receptor agonist, 2.5 nmol in 1 μl) was directly injected to unilateral striatum. Melatonin (10 mg/kg) was administrated intraperitoneally 1 h before and 1, 3, and 5 h after intrastriatal kainate injection in adult Sprague-Dawley rats. Three days after kainate injection, a significant neuronal damage was found, as determined by Nissl staining and the TUNEL method, not only in the injected striatum, but also in the ipsilateral neighboring cortex. The kainate-induced cortical apoptotic neuronal death was significantly attenuated by treatment with melatonin compared with the vehicle control group. However, no detectable changes were observed in the contralateral side of the brain in either vehicle- or melatonin-treated rats. Moreover, the biochemical results indicated that kainate can indeed induce oxidative stress, such as a decrease in the content of total glutathione (GSH), oxidized glutathione (GSSG), and an increase in the ratio of GSSG/GSH in the striatum and cortex compared with the contralateral brain regions. In the kainate-injected striatum, melatonin did not reduce the oxidative stress, but in the neighborhood of injected area-cortex, kainate-induced oxidative stress was significantly reduced by melatonin. Enhancement of glutathione-peroxidase activity was induced by intrastriatal kainate injection, not only in the cortical area of control and melatonin-treated rats, but also in striatum of control rats. However, a large elevation was found in the melatonin-treated cortex. Taking the morphological and biochemical data together, the present results suggest that melatonin functions as an antioxidant by upregulating the glutathione antioxidative defense system, thereby reducing neuronal death caused by excitotoxicity and preventing the kainate-induced damage from spreading to adjacent brain regions. Received: 16 December 1997 / Accepted: 30 July 1998     

Dual effects of melatonin on barbiturate-induced narcosis in rats

Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action.     

Protective effects of melatonin on long-term administration of fluoxetine in rats

The degree and consequence of tissue injury are highly regarded during long-term exposure to selective antidepressant fluoxetine. Melatonin has been shown to palliate different lesions by scavenging free radicals, but its role in the reduction of the fluoxetine-induced injuries has been little known.Thirty-six mature male Wistar rats were randomly assigned into control and experimental groups. The experimental rats were included as following; 24 mg/kg/bw fluoxetine for 4 weeks; 1 mg/kg/bw melatonin for 4 weeks; fluoxetine + 1-week melatonin, fluoxetine + 2-week melatonin and fluoxetine + 4-week melatonin. In the current experiment, we investigated weight gain, hematological and biochemical parameters, pathological injuries and oxidative status.We noted the positive effect of melatonin in weight loss of fluoxetine-treated rats (p < 0.05). The significant reduction of superoxide dismutase, glutathione peroxidase, catalase activities in blood, liver, and kidneys and changes in serum total antioxidant capacity caused by fluoxetine were reversed by melatonin (p < 0.05). Melatonin reduced the increased lipid peroxidation and transaminase activity in rats received fluoxetine (p < 0.05). We also showed the potency of fluoxetine in inducing leukopenia, thrombocytopenia and hypochromic and macrocytic anemia which was blunted by melatonin. Both RBCs and platelets indices were also corrected. Rats received melatonin in combination with fluoxetine showed a reduction in the severity of degeneration and inflammatory changes in different tissues, brain, heart, liver, lungs, testes and kidneys as compared to the fluoxetine group.Therefore, melatonin fundamentally reversed the side effects of fluoxetine in the rat model which is comparable to human medicine.