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.     

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.     

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     

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.

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。     

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     

去松果体后成年大鼠学习记忆及侧脑室室管膜下区神经干细胞增殖的变化

目的观察松果体切除对学习记忆及侧脑室室管膜下区(SVZ)神经干细胞增殖的影响。方法将30只成年健康雄性Sprague-Dawley大鼠随机分为非手术、假手术及去松果体组,每组大鼠10只。在建立动物模型16d后,连续5d测定大鼠在Morris水迷宫的学习记忆能力,继之用免疫组织化学方法观察SVZ的增殖细胞核抗原(PCNA)阳性细胞的变化。结果去松果体组大鼠在Morris水迷宫泳游的逃避潜伏期及在原平台象限游泳距离的百分比均较非手术组或假手术组大鼠的明显延长或减少(P<0.01)。去松果体大鼠SVZ的PCNA阳性细胞数也明显低于非手术组或假手术组大鼠(P<0.01)。结论本研究首次观察到,去松果体使体内褪黑素减少,可导致学习记忆功能及SVZ神经干细胞增殖能力出现相似的明显下降趋势,说明褪黑素是确保学习记忆及神经发生得以正常进行的重要激素之一;提示褪黑素可能直接通过作用于神经干细胞上的相应受体以及间接通过提高基底前脑胆碱能系统功能来促进神经干细胞增殖,进而提高嗅觉记忆功能。     

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.     

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.     

Suppression of apoptosis and oxidative stress by deprenyl and estradiol in aged rat liver

Aging is accompanied by significant structural and functional transformations of all organs and systems. Age-associated increase in apoptotic behavior may cause disease. Older cells are more susceptible to endogenous oxidative damage, and oxidative stress is a potent inducer of apoptosis. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has anti-oxidant, anti-apoptotic and neuroprotective effects. Estrogen is also a neuroprotective and anti-oxidant hormone. The objectives of this study were to determine whether the anti-oxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat livers. In this study, ovariectomized female Wistar albino rats were divided into six groups as follows; young (3 months old) saline-treated control, aged (24 months old) saline-treated control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and aged sham controls. All rats except for the sham group were treated for 21 days. Determination of oxidative stress parameters was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed. The results were analyzed by one-way ANOVA post hoc Bonferroni test. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation and increased superoxide dismutase activity in the liver relative to aged control and sham rats (P<0.05). The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat liver by decreasing oxidative stress.     

Dimethoate-induced biochemical and histopathological changes in the liver of rats

Dimethoate is an organophosphorus insecticide and acaricide used for the control of a wide range of insects, including houseflies and mites, on a variety of fruits, vegetables, field and forestry crops. The aim of the current study was to evaluate the subchronic toxicity of orally administered dimethoate in Wistar albino rats, based on the histopathological and biochemical findings in the liver. The animals of the exposed groups were fed with laboratory chow combined with 2, 8 or 20 mg/kg body weight/day dimethoate for 90 consecutive days under controlled laboratory conditions. At the end of the experiment, body weight gain, absolute and relative liver weights, liver cholinesterase activities and total protein levels were determined. Histopathological changes in the liver were also determined using a light microscope. Results showed that there were decreases in relative liver weights of exposed rats. Although liver total protein levels were significantly increased, liver cholinesterase activities were decreased in all exposed groups. Dimethoate caused dose-related histopathological changes such as mononuclear cell infiltration, congestion, an enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, an increase in the number of Kupffer cells, cytoplasmic vacuolization and degeneration in nuclei in the liver of exposed rats. These effects did not vary between the sexes.     

Effect of melatonin on total food intake and macronutrient choice in rats

Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal gland, is used to alleviate the symptoms of jetlag and treat sleeping problems. The objective of the present study was to examine the effects of a 7-h phase-shift from the natural peak of melatonin secretion on total food intake and macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided in three dietary groups, each group offered a simultaneous and different choice of a carbohydrate- and a protein-rich diet. Macronutrient intakes following intraperitoneal administration of four doses of melatonin (3000, 6000, 10 000 and 15 000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h postinjection) and long-term (12 h postinjection) nocturnal total food intake in both male and female rats, mainly with the two highest doses. This effect of melatonin was mainly due to a short-term increase of intake across all carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and across genders. This consistent effect of melatonin on the intake of carbohydrate-rich diets with contrasting sensory attributes rules out the possibility that melatonin acts on sensorymotor pathways, thus suggesting that melatonin's effect on food intake is controlled by the carbohydrate content of the diet. In contrast, melatonin could be affecting some sensory or motor processes peculiar to the ingestion of protein since it increased protein-rich diet intake inconsistently across the various preparations (casein, soy isolate, and egg protein) as well as genders. This evidence supports the view that melatonin acts as a time indicator, reinforcing the animals with a “night cue”, and favors predominant carbohydrate intake normally occurring at the beginning of the activity period.     

实验性肝硬化鼠血浆胰高血糖素的动态变化与钠潴留

本文纵向观察了四氯化碳致鼠肝硬化模型血清甘胆酸、血浆胰高血糖素水平、平均动脉压、醛固酮以及钠排泄的变化。     

Metformin and melatonin improve histopathological outcome of NMU-induced mammary tumors in rats

Objective

Numerous reports showed inhibition of carcinogenesis after metformin (MF) and melatonin (MEL) administration. However, most in vivo studies used standard diet type, with relatively low fat content. As increase in fat intake may have a considerable impact on malignant transformation, we evaluated the effects of these two substances in a model of mammary carcinogenesis in rats fed a high-fat diet (10%).

Lipid peroxidation in the brain and liver of rats during acute stress and melatonin treatment

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 19–23, July, 2004