Protective effects of chronic melatonin treatment against renal injury in streptozotocin-induced diabetic rats

The aim of this study was to investigate the effects of melatonin as an antioxidant, on prevention and treatment of streptozotocin (STZ)-induced diabetic renal injury in rats. Male Wistar rats were divided into four groups: (1) untreated, (2) melatonin-treated, (3) untreated diabetic (UD), (4) melatonin-treated diabetic (MD). Experimental diabetes was induced by single dose (60 mg/kg, i.p.) STZ injection. For 3 days prior to administration of STZ, melatonin was injected (200 microg/kg/day, i.p.); these injections were continued until the end of the study (4 weeks). Malondialdehyde (MDA) levels as a marker of lipid peroxidation were significantly increased in the renal homogenates of UD animals and decreased after melatonin administration. The activity of the antioxidative enzyme glutathione peroxidase (GSH-Px) was significantly reduced in UD rats. Melatonin treatment reversed STZ-induced reduction of GSH-Px activity without having an effect on blood glucose. Upon histopathological examination, it was observed that the melatonin treatment prevented the renal morphological damage caused by diabetes. Upon immunohistochemical investigation, glomerular anti-laminin beta1 staining decreased in MD rats. Additionally, no tubular anti-IGF-1 staining was observed in melatonin-treated rats. In conclusion, chronically administered melatonin reduced renal injury in STZ-induced diabetic rats and thus it may provide a useful therapeutic option in humans to reduce oxidative stress and the associated renal injury in patients with diabetes mellitus.     

Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus

There is a clearly documented link between diabetic complications and lipid peroxidation. Hyperglycemia causes a reduction in levels of protective endogenous antioxidants and increases generation of free radicals. The present study was carried out to compare the protective effects of melatonin and vitamin E against streptozocin (STZ)-induced diabetes in rats. Melatonin was administered s.c. (100 microg/kg) whereas vitamin E was given i.p. (100 mg/kg) after induction of diabetes with STZ (60 mg/kg). Plasma total cholesterol, triglyceride and low density lipoprotein (LDL) levels were increased in STZ group while both melatonin and vitamin E injection caused a significant decrease in the levels of all these parameters. The lipid lowering effect of melatonin was greater than that of vitamin E. Melatonin caused a significant decrease in brain, liver and kidney tissue malondialdehyde (MDA) levels which were increased because of STZ-induced diabetes. Vitamin E also reduced elevated MDA concentrations in diabetic rat tissues, but the effect of melatonin was more potent than that of vitamin E. Furthermore, treatment of diabetic rats with melatonin increased brain and kidney glutathione peroxidase (GSH-Px) activity to the levels below that of control rats. Vitamin E was found to be less effective on GSH-Px activity levels in brain and kidney than melatonin whereas it was more potent than melatonin in liver. In summary, melatonin prevents many diabetic complications by reducing oxidative stress and protects organisms from oxidative damage and dyslipidemia. Considering the much lower molar concentration of melatonin compared with vitamin E, melatonin seems to be a more potent antioxidant, especially in the brain and kidney.     

桃叶珊瑚苷对糖尿病大鼠线粒体的抗氧化作用

目的 研究桃叶珊瑚苷对链脲佐菌素(STZ)诱导的糖尿病大鼠血糖和线粒体抗氧化能力的影响. 方法 通过STZ腹腔注射建立糖尿病大鼠模型,将其随机分为糖尿病组、STZ低剂量组和STZ高剂量组,并与空白对照组比较.观察桃叶珊瑚苷治疗前后糖尿病大鼠的形态、体质量、血糖、线粒体内脂质过氧化和抗氧化体系的变化. 结果 与空白对照组比较,糖尿病大鼠血糖、MDA显著升高,CAT、GSH-Px、SOD活力显著下降;桃叶珊瑚苷治疗后血糖、MDA显著降低,CAT、GSH-Px、SOD活力显著升高. 结论 桃叶珊瑚苷能显著降低糖尿病大鼠的血糖值,改善线粒体的抗氧化水平,是一种潜在的防治糖尿病药物.     

Protective effects of chronic melatonin treatment against renal ischemia/reperfusion injury in streptozotocin-induced diabetic rats.

AIMS: The purpose of this study was to investigate the effects of chronic administration of melatonin on renal ischemia/reperfusion (IR) injury in streptozotocin (STZ)-induced diabetic rats. METHODOLOGY: Male Sprague-Dawley rats were divided into six groups: control (C), diabetes mellitus (DM), control+IR (C+IR), DM+IR, Melatonin+IR (Mel+IR), DM+Mel+IR. Diabetic and non-diabetic rats were given melatonin 4 mg/kg/day, i.p., for 15 days. The left renal artery and vein of rats were occluded for 30 min at the 18th day, followed by 24 h of reperfusion. RESULTS: In comparison with control group, the levels of malondialdehyde (MDA), protein carbonyl (PC) and and nitric oxide (NO) were determined to be higher in the renal homogenates of DM, DM+IR and C+IR groups. MDA and NO levels were found to be similar in the DM+melatonin+IR and control groups. The most significant histological damage was found in the DM+IR group and this damage was significantly reduced by melatonin. CONCLUSION: Chronic melatonin treatment reduces renal injury by reducing lipid oxidation and NO production in STZ-induced diabetic rats exposed to IR.     

Oxidative stress in diabetic rats induced by streptozotocin: Protective effects of melatonin

Abstract: We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 μg/kg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution, pH 4.0) and melatonin (melatonin 100, 100 μg/kg/day i.p.; melatonin 200, 200 μg/kg/day i.p.) beginning 3 days before diabetes induction and continuing until the end of the study (8 weeks). The parameters analysed to evaluate oxidative stress and the diabetic state were a) for oxidative stress, changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes, changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL-cholesterol, HDL-c), percentage of glycosylated hemoglobin (Hb%), and plasma fructosamine. The injection of STZ caused significant increases in the levels of glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol, triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased the levels of HDL-c and the GSH content in erythrocytes. The melatonin 100 dose reduced significantly all these increases, except the percentage of glycosylated hemoglobin. With regard to the decreases of plasma HDL-c and GSH content in erythrocytes, this melatonin dose returned them to normal levels. The melatonin 200 dose produced similar changes, though the effects were especially noticeable in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin (P < 0.001 vs diabetes), and fructosamine (31% vs. diabetes). This dose also reversed the decreases of HDL-c and GSH in erythrocytes. Both doses of melatonin caused significant reduction of the percentage of glycosylated hemoglobin in those groups that were non-diabetic. These illustrate the protective effect of melatonin against oxidative stress and the severity of diabetes induced by STZ. In particular, this study confirms two facts: 1) the powerful antioxidant action of this pineal indole and 2) the importance of the severity of oxidative stress to maintain hyperglycemia and protein glycosylation, two pathogenetic cornerstones indicative of diabetic complications. Melatonin reduces remarkably the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which gives hope to a promising perspective of this product, together with other biological antioxidants, in the treatment of diabetic complications where oxidative stress, either in a high or in a low degree, is present.     

Nerve conduction and antioxidant levels in experimentally diabetic rats: effects of streptozotocin dose and diabetes duration

Oxidative stress supposedly plays a role in the pathogenesis of diabetic neuropathy. We have studied whether a variation in the streptozotocin (STZ) dose or diabetes duration affects the outcome of measurements of oxidative damage in relation to nerve conduction. In experiment 1, we induced diabetes in rats using 40 or 60 mg/kg STZ intravenously and assessed sciatic nerve conduction velocity. After 18 weeks, we measured plasma malondialdehyde (MDA) and red blood cell (RBC) and nerve glutathione levels. We observed a dose-dependent effect of STZ on body weight, and to a lesser extent on nerve conduction, but not on RBC or nerve glutathione and plasma MDA. In experiment 2, we administered a fixed dose of STZ (40 mg/kg) and measured antioxidants and MDA in RBCs, plasma, and sciatic nerve after 2, 4, 8, and 18 weeks in diabetic and control rats. RBC glutathione decreased in diabetic animals initially, but did not differ from control values after week 4. Plasma total glutathione increased until week 8. The ratio of total to oxidized glutathione in the sciatic nerve from diabetic animals paralleled the decrease observed in RBCs, and subsequently increased compared with controls. Nerve catalase increased in diabetic animals. Endoneurial MDA remained unchanged, whereas plasma MDA increased and RBC superoxide dismutase (SOD) decreased in the diabetic group. We conclude that differences in antioxidant levels between STZ-diabetic and control rats depend on the duration of hyperglycemia. Furthermore, dose-related effects of STZ on nerve conduction are not reflected in endoneurial lipid peroxidation or glutathione.     

L-精氨酸对糖尿病大鼠肝、心肌及膈肌线粒体自由基损伤的保护作用

目的探讨L-精氨酸(L-Arg)对糖尿病大鼠肝脏、心肌及膈肌线粒体自由基损伤的保护作用. 方法给大鼠腹腔注射四氧嘧啶制备糖尿病模型,随机分为糖尿病组、L-Arg治疗组及正常对照组;用药4 w末测定三组大鼠肝脏、心肌及膈肌细胞线粒体中Mn-SOD、GSH-Px活性和MDA含量及膈肌线粒体内GSH含量.结果糖尿病组较正常组,大鼠肝、心肌、膈肌线粒体内GSH-Px活性显著降低(P＜0.01,P＜0.05,P＜0.001),MDA含量显著升高(P＜0.01,P＜0.05,P＜0.01),肝、膈肌线粒体Mn-SOD活性(均P＜0.01)及膈肌线粒体GSH含量(P＜0.05)也明显降低;与模型组比较,L-Arg可显著增加糖尿病大鼠肝、心肌、膈肌线粒体GSH-Px活性(P＜0.05,P＜0.05,P＜0.001)及肝、膈肌线粒体Mn-SOD活性(均P＜0.001),并使膈肌线粒体MDA含量显著降低(P＜0.01),而GSH含量明显升高(P＜0.001). 结论糖尿病大鼠肝、心肌、膈肌线粒体内自由基生成增多;L-Arg可通过提高肝、心肌、膈肌细胞线粒体中自由基清除酶的活性来加速自由基的清除,提高机体的抗氧化能力,从而保护机体功能免受氧化损伤.     

<Emphasis Type="Italic">Moringa oleifera</Emphasis> supplemented diet modulates nootropic-related biomolecules in the brain of STZ-induced diabetic rats treated with acarbose

There are strong correlations between diabetes mellitus and cognitive dysfunction. This study sought to investigate the modulatory effects of Moringa oleifera leaf (ML) and seed (MS) inclusive diets on biomolecules [acetylcholinesterase (AChE), butyrylcholinesterase (BChE)] angiotensin-I converting enzyme (ACE), arginase, catalase, glutathione transferase (GST) and glutathione peroxidase (GSH-Px) activities, glutathione (GSH) and nitric oxide (NO) levels] associated with cognitive function in the brain of streptozotocin (STZ)-induced diabetic rats treated with acarbose (ACA). The rats were made diabetic by intraperitoneal administration of 0.1 M sodium-citrate buffer (pH 4.5) containing STZ [60 mg/kg b.w (BW)] and fed with diets containing 2 and 4% ML/MS. Acarbose (25 mg/kg BW) was administered by gavage daily for 14 days. The animals were distributed in eleven groups of eight animals as follows: control, STZ-induced, STZ?+?ACA, STZ?+?2% ML, STZ?+?ACA?+?2% ML, STZ?+?4% ML, STZ?+?ACA?+?4% ML, STZ?+?2% MS, STZ?+?ACA?+?2% MS, STZ?+?4% MS, STZ?+?ACA?+?4% MS. There were marked increase in AChE, BChE, arginase, ACE and concomitant decrease in catalase, GST, GSH-Px, activities and NO levels in STZ-diabetic group compared with the control. However, there was a decrease in AChE, BChE and ACE activities and concomitant increase in the antioxidant molecules in the groups fed with supplemented diets treated with/without ACA compared with the STZ-diabetic group. These findings suggest that ML/MS supplemented diet could prevent cognitive dysfunction-induced by chronic hyperglycemia.     

Melatonin reduces lipid peroxidation and nitric oxide during irradiation-induced oxidative injury in the rat liver

Radiation therapy is a popular and useful tool in the treatment of cancer. Melatonin participates in the regulation of a number of important physiological and pathological processes. Melatonin, a powerful endogenous antioxidant, plays a role in the reduction of oxidative damage. Thirty adult rats were divided into five equal groups. On the day of the experiment, groups I and II were injected with 5 or 10 mg/kg melatonin, respectively, while group III received isotonic NaCl solution. Thirty minutes later, groups I, II and III were exposed to 6.0 Gy whole body ionizing radiation in a single fraction. Group IV was injected with 5 mg/kg melatonin but was not irradiated. The final group was reserved as sham treated. Liver malondialdehyde (MDA) and nitric oxide (NO*) levels were measured in all groups. Whole body irradiation caused a significant increase in liver MDA and NO* levels. Hepatic MDA and NO* levels in irradiated rats that were pretreated with melatonin (5 or 10 mg/kg) were significantly decreased. Malondialdehyde and NO* levels were reduced in a dose-related manner by melatonin. The data show that melatonin reduces liver damage inflicted by irradiation when given prior to the exposure to ionizing radiation. The radioprotective effect of melatonin is likely achieved by its ability to function as a scavenger for free radicals generated by ionizing radiation.     

Effect of aminoguanidine on lipid peroxidation in streptozotocin-induced diabetic rats.

Diabetes mellitus is postulated to be associated with increased lipid peroxidation, which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine (AMGN), the prototype inhibitor of advanced glycosylation end product (AGE) formation, has been recently shown to prevent oxidative modification of low-density lipoprotein (LDL) in vitro at a moderate concentration. It is unknown whether AMGN may act as an antioxidant against lipid peroxidation under hyperglycemia in vivo. To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN (1 g/L in drinking water) or vitamin E (400 mg/d for 5 d/wk) to streptozotocin (STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II (FOX method) and red blood cell (RBC) membrane malondialdehyde (MDA) and related aldehydes as thiobarbituric acid-reactive substances (TBARS). Plasma lipid hydroperoxide was higher in STZ-induced diabetic rats versus control rats (mean +/- SD, 7.53 +/- 2.03 v 5.62 +/- 0.44 micromol/L, P < .05; n = 8 to 14). RBC membrane TBARS were also higher in STZ-induced diabetic rats than in control rats (2.67 +/- 0.46 v 1.81 +/- 0.19 nmol/mL, P < .05). Plasma lipid hydroperoxide was lower in AMGN-treated (6.23 +/- 0.59 micromol/L, P < .05) and vitamin E-treated (5.29 +/- 0.27 micromol/L, P < .05) diabetic rats than in untreated diabetic rats. RBC membrane TBARS were also lower in AMGN-treated (1.93 +/- 0.12 nmol/mL, P < .05) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, cholesterol, and triglyceride levels among diabetic groups. Although the mechanism(s) of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN may have an additional beneficial effect as an antioxidant against lipid peroxidation in a prevention trial for diabetic vascular complications.     

Diabetes enhances oxidative stress-induced TRPM2 channel activity and its control by N-acetylcysteine in rat dorsal root ganglion and brain

N-acetylcysteine (NAC) is a sulfhydryl donor antioxidant that contributes to the regeneration of glutathione (GSH) and also scavengers via a direct reaction with free oxygen radicals. Recently, we observed a modulatory role of NAC on GSH-depleted dorsal root ganglion (DRG) cells in rats. NAC may have a protective role on oxidative stress and calcium influx through regulation of the TRPM2 channel in diabetic neurons. Therefore, we investigated the effects of NAC on DRG TRPM2 channel currents and brain oxidative stress in streptozotocin (STZ)-induced diabetic rats. Thirty-six rats divided into four groups: control, STZ, NAC and STZ + NAC. Diabetes was induced in the STZ and STZ + NAC groups by intraperitoneal STZ (65 mg/kg) administration. After the induction of diabetes, rats in the NAC and STZ + NAC groups received NAC (150 mg/kg) via gastric gavage. After 2 weeks, DRG neurons and the brain cortex were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM2 currents in the DRG following diabetes induction with STZ were gated by H₂O₂. TRPM2 channel current densities in the DRG and lipid peroxidation levels in the DRG and brain were higher in the STZ groups than in controls; however, brain GSH, GSH peroxidase (GSH-Px), vitamin C and vitamin E concentrations and DRG GSH-Px activity were decreased by diabetes. STZ + H₂O₂-induced TRPM2 gating was totally inhibited by NAC and partially inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA) and 2-aminoethyl diphenylborinate (2-APB). GSH-Px activity and lipid peroxidation levels were also attenuated by NAC treatment. In conclusion, we observed a modulatory role of NAC on oxidative stress and Ca²⁺ entry through the TRPM2 channel in the diabetic DRG and brain. Since excessive oxidative stress and overload Ca²⁺ entry are common features of neuropathic pain, our findings are relevant to the etiology and treatment of pain neuropathology in DRG neurons.     

Carvedilol improved diabetic rat cardiac function depending on antioxidant ability

The risk for cardiovascular disease is significantly high in diabetes mellitus. Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has a close connection with antagonizing oxidative stress destroy in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant and free radical scavenger properties. To study the effect of carvedilol on the antioxidant status and expression of Bcl-2 in healthy and diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage (1 or 10mg/kg/d) carvedilol-administrated for 5 weeks, hemodynamic parameters, the levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and expression of Bcl-2 mRNA in the cardiac tissues of all six groups were measured. Diabetic rats had higher left ventricular end diastolic pressure (LVEDP), lower maximal rate of rise/fall left ventricle pressure development and decline (+/-dP/dtmax). These parameters were improved by administration of carvedilol. Diabetic rats showed elevated MDA level and CAT activity, but lower activities of SOD and GSH-Px. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicate that carvedilol improves cardiac function via its antioxidant property in diabetic rats partly.     

Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF expression in retinas of STZ–induced early diabetic rats

ObjectiveTo investigate the effects of puerarin on the activity of superoxide dismutase (SOD), and expressions of advanced glycation end-product (AGE) receptor (RAGE) and vascular endothelial growth factor (VEGF) in retinas of streptozotocin (STZ)-induced early diabetic rats.MethodsDiabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ. Rats were randomly divided into normal (control), diabetic (DM), and DM+ puerarin groups. After intra-gastric administration of puerarin (500 mg/kg/day for 4 weeks), levels of SOD and malondialdehyde (MDA) were determined in serum and retina. mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-time polymerase chain reaction (RT-PCR) (mRNA) and Western blot analysis (protein levels).ResultsThere was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups (P<0.05). After treatment with puerarin, SOD activity increased and MDA content decreased in this group (P<0.05). mRNA and protein expression levels of RAGE and VEGF in the DM group were significantly higher than those of the other groups (P<0.05), and decreased after puerarin treatment (P<0.05).ConclusionsPuerarin is able to enhance SOD activity, and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic rats.     

Pentoxifylline diminishes the oxidative damage to renal tissue induced by streptozotocin in the rat

Oxidative damage has been suggested to be a contributing factor in the development to diabetic nephropathy (DN). Recently, there has been evidence that pentoxifylline (PTX) has free radical-scavenging properties; thus, its anti-inflammatory and renoprotective effects may be related to a reduction in reactive oxygen species production. It is likely that the pharmacological effects of PTX include an antioxidant mechanism as shown in in vitro assays. The aim of this study was to evaluate whether the reported renoprotective effects of PTX could be the result of its antioxidant actions in streptozotocin (STZ)-induced DN in rats. The administration of PTX over a period of 8 weeks, in addition to displaying renoprotective effects, caused a significant reduction in lipoperoxide levels (LPOS) in the diabetic kidney (P < 0.05), compared to untreated rats. These levels were comparable to those in the healthy kidney of experimental animals (P > 0.05). All untreated STZ rats exhibited an increase in LPOS as opposed to healthy controls (H) (P < 0.001). The total antioxidant activity (TAA) in plasma was increased significantly already after 2 days of STZ (P < 0.05). When we examined the progression of TAA in STZ rats, there was a significant decrease over 8 weeks (P < 0.05). PTX treatment caused an increase in TAA when compared to untreated STZ rats (P < 0.05). Renal hypertrophy was less evident in PTX-treated STZ than in untreated STZ rats, evaluated by kidney weight/body weight ratio. These results indicate that PTX decreases the oxidative damage induced by these experimental procedures and may increase antioxidant defense mechanisms in STZ-induced diabetes in rats.     

Effect of I-deprenyl and gliclazide on oxidant stress/antioxidant status and dna damage in a diabetic rat model

BACKGROUND: This study investigates the possible effect of monoamine oxidase inhibitor (MAOI), selegyline (l-deprenyl), in combination with oral antidiabetic-gliclazide (OAD), in preventing oxidative stress in streptozotocin-induced diabetes model in male Swiss Albino rats by measuring oxidant stress/ DNA damage and antioxidant levels. METHODS: Diabetic rats were divided into four groups (n = 10) as (1) diabetic untreated (DM), (2) deprenyl treated (DM + D), (3) gliclazide treated (DM + O), and (4) gliclazide and deprenyl treated (DM + O + D). Controls were divided into two groups (n = 8) (1) untreated (C), and (2) deprenyl treated (C + D). Gliclazide 5 mg/kg and/or MAOI 0.25 mg/kg daily were given orally by gavage for 4 weeks. At the end of the 12th week, catalase and superoxide dismutase (SOD) levels in erythrocyte lysates (EL); total antioxidant status (TAS), 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamin A and E levels in plasma, MDA, and MAO in liver homogenates were determined. RESULTS: Diabetic rats showed a decrease in EL-SOD, plasma TAS, and vitamin E, and an increase in plasma 8-OHdG, plasma, and liver MDA levels (p < 0.05). Gliclazide and/or deprenyl decreased 8OHdG levels and increased antioxidant levels and survival when compared with untreated diabetic rats (p < 0.05). The lowest 8-OHdG levels were determined in the DM +O + D group. CONCLUSIONS: The combined treatment of deprenyl and gliclazide may contribute to the control of the physiopathological mechanisms underlying both the process of aging and type 2 diabetes by reducing oxidant stress and DNA damage, improving antioxidant status, and increasing survival, and may have implications for further clinical studies.     

The Effects of Combined Treatment of Antioxidants on the Liver Injury in STZ Diabetic Rats

The aim of this study was to examine whether an antioxidant combination of vitamin C, vitamin E, and sodium selenate (Se) has an effect on the liver of diabetic rats. Vitamin C, vitamin E, and Se were administered for 30 days to streptozotocin (STZ)-induced diabetic and control groups. In the STZ diabetic group, blood glucose levels, liver lipid peroxidation (LPO), and nonenzymatic glycosylation (NEG) levels increased, but blood and liver glutathione levels decreased. On the other hand, combined antioxidant treatment reversed these effects. In the diabetic group, some degenerative changes were observed by light and electron microscopic examinations, but the degenerative changes decreased in the diabetic group given antioxidant combination. Proliferating cell nuclear antigen (PCNA) immunohistochemistry showed that the number of proliferative hepatocytes increased significantly with antioxidant treatment. It was concluded that combined treatment with vitamin C, vitamin E, and Se has a curative effect against the hepatotoxicity produced by STZ-induced diabetes.     

Protective Effects of Thymoquinone and Melatonin on Intestinal Ischemia–reperfusion Injury

Background/Aim:

In the present study, we aimed to compare the potential protective effects of thymoquinone and melatonin by using equivalent dose, on oxidative stress-induced ischemia–reperfusion (IR) injury in the intestinal tissue of rats.

Materials and Methods:

The study was performed using 32 male Wistar–Albino rats (weighing 180–200 g) randomly divided into four groups: Group I, sham group; Group II, IR group; Group III, IR with melatonin group; and Group IV, IR with thymoquinone group. After laparotomy, ischemia and reperfusion were performed for 60 and 120 min, respectively, on all the groups. Intestinal tissue sections were stained using routine histological methods and examined under the light microscope. In addition, the sections were immunohistochemically stained using the TUNEL method for determination of apoptosis. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) levels in the intestinal tissue were also measured.

Results:

The IR group had significantly elevated tissue SOD activity, GSH-Px activity, and MDA levels compared with the sham group. Administration of thymoquinone and melatonin efficiently reduced these increases. Statistically significant number of apoptotic cells was observed in the intestinal tissue of IR group rats compared with the sham group. Treatment with thymoquinone and melatonin markedly reduced the number of apoptotic cells.

Conclusion

The effects of melatonin and thymoquinone on IR-induced oxidative stress in rat intestines were similar. Our findings suggest that melatonin and thymoquinone protect against IR-induced injury to intestinal tissues.     

褪黑素对糖尿病患者氧化应激抑制作用和糖脂代谢影响的观察

目的 探讨褪黑素对糖尿病患者氧化应激的抑制作用及糖脂代谢的影响。 方法 1998-12～2003-04东南大学附属中大医院采用随机、单盲、安慰剂平行对照的方法,观察褪黑素及安慰剂对91例糖尿病患者血清丙二醛(MDA)及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的影响,并分析上述影响与糖脂代谢变化之间的关系。 结果 治疗前糖尿病患者血清SOD、GSH-Px水平下降,MDA水平上升。褪黑素组8周处理后血清SOD和GSH-Px水平上升,而MDA水平明显下降,与处理前相比差异有显著;安慰剂组处理前后患者血清SOD、GSH-Px及MDA水平无明显变化。褪     

L-精氨酸对糖尿病大鼠肝损伤的保护作用

目的探讨L-精氨酸(L-Arg)对糖尿病大鼠肝脏损伤的保护作用。方法给大鼠腹腔注射四氧嘧啶制备糖尿病模型,随机分为糖尿病组、L-Arg治疗组及正常对照组;用药4周末处死大鼠,检测肝细胞线粒体超氧化物歧化酶(Mn-SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,肝组织细胞一氧化氮合酶(NOS)、Na -K -ATPase、Ca2 -ATPase活性以及NO含量。结果与正常组比较,糖尿病组大鼠肝细胞线粒体Mn-SOD、GSH-Px活性明显降低,MDA含量显著升高,肝组织细胞内NOS、Na -K -ATPase、Ca2 -ATPase活性明显降低;与糖尿病组比较,L-Arg治疗组大鼠肝细胞线粒体Mn-SOD、GSH-Px活性明显升高,且肝组织细胞内NOS、Na -K -ATPase、Ca2 -ATPase活性及NO含量显著升高。结论L-Arg对糖尿病大鼠肝脏损伤具有一定的保护作用。     

Moderate exercise with a dietary vitamin C and e combination protects against streptozotocin-induced oxidative damage to the kidney and lens in pregnant rats.

Moderate exercise and vitamin C and E (VCE) supplementation can be beneficial to diabetes due to reducing free radical production in lens and kidney of diabetic pregnant rats. We investigated the effect of VCE supplementation and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the kidneys and lens of STZ-induced diabetic pregnant rats. Fifty female Wistar rats were used and were randomly divided into five groups. First and second were used as the control and pregnant control group. Third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Plasma, lens, and kidney samples were taken from all animals on day 20. Exercise and administration of VCE to pregnant diabetic rats resulted in significant decrease in the albumin and total protein values and the elevated MDA, plasma creatinine, and urea levels as an indicator of oxidative stress and renal functional parameters. Exercise and VCE supplementation also increased glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in the kidney, GSH-Px and GSH in the lens, the albumin and total protein values in plasma. In the diabetic pregnant animals, the decreased vitamins A and E concentration and GSH levels in kidney, creatinine, and urea values in plasma did not improve through exercise only although their concentrations were increased by VCE supplementation. Kidney weight did not also affect either by exercise or VCE supplementation. In conclusion, these results suggest that exercise plus VCE affects antioxidant metabolism and reduces lipid peroxidation, thereby improving the damage caused by oxidative stress involved in the pathogenesis of lens and kidney in diabetic pregnant rats. Moderate exercise with dietary VCE may play a role in preventing nephropathy and cataract formation in diabetic pregnant rat.