Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism

Objectives: Reactive oxygen species (ROS) have been implicated in the development of streptozotocin (STZ)-induced diabetes mellitus. Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is an antioxidant. An investigation was made of the effects of SDG on the development of STZ-induced diabetes in rat, to determine if SDG can prevent/reduce the development of diabetes and if this prevention/reduction is associated with reduction in oxidative stress.Design and Methods: The rats were divided into 4 groups: Group I, Control; Group II, SDG (22 mg/kg body wt, orally) for 24 days; Group III, STZ (80 mg/kg intraperitoneally); Group IV, SDG in the dose similar to Group II three days prior to STZ and 21 days thereafter. Oxidative stress was assessed by measuring serum and pancreatic lipid peroxidation product malondialdehyde (MDA), pancreatic antioxidant reserve (pancreatic-CL) and oxygen free radical producing activity of white blood cells (WBC-CL). A diagnosis of diabetes was made on the basis of glucosuria and was confirmed at the time of sacrifice (21 days after STZ treatment) by the presence of hyperglycemia. At the end of the protocol blood samples were collected for estimation of glucose, MDA and WBC-CL, and pancreas were removed for estimation of MDA and antioxidant reserve.Results: Incidence of diabetes was 100% in Group III and 25% in Group IV. SDG prevented the development of diabetes by 75%. Development of diabetes was associated with an increase in serum and pancreatic MDA, and in WBC-CL, and a decrease in pancreatic antioxidant reserve. Prevention of diabetes by SDG was associated with a decrease in serum and pancreatic MDA and WBC-CL and an increase in pancreatic antioxidant reserve.Conclusions: These results suggest that STZ-induced diabetes is mediated through oxidative stress and that SDG is effective in reducing the STZ-induced diabetes mellitus.     

Oxidative stress as a mechanism of teratogenesis

Emerging evidence shows that redox-sensitive signal transduction pathways are critical for developmental processes, including proliferation, differentiation, and apoptosis. As a consequence, teratogens that induce oxidative stress (OS) may induce teratogenesis via the misregulation of these same pathways. Many of these pathways are regulated by cellular thiol redox couples, namely glutathione/glutathione disulfide, thioredoxinred/thioredoinox, and cysteine/cystine. This review outlines oxidative stress as a mechanism of teratogenesis through the disruption of thiol-mediated redox signaling. Due to the ability of many known and suspected teratogens to induce oxidative stress and the many signaling pathways that have redox-sensitive components, further research is warranted to fully understand these mechanisms.     

The effects of rosiglitazone on oxidative stress and lipid profile in left ventricular muscles of diabetic rats

We investigated the effect of rosiglitazone (RSG), a high-affinity ligand for the peroxisome proliferator-activated receptor gamma which mediates insulin-sensitizing actions, on the lipid profile and oxidative status in streptozotocin (STZ)-induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were randomly divided into an untreated control group (C), a C + RSG group which was treated with RSG (4 mg kg(-1)) two times a day by gavage, a diabetic group (D) that was treated with a single intraperitoneal injection of STZ (45 mgkg(-1)), D + RSG group which were treated with RSG two times a day by gavage, respectively. Lipid profiles, HbA(1c) and blood glucose levels in the circulation and malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in left ventricular muscle were measured. Treatment of D rats with RSG resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA(1c) levels in D + RSG group reached the C rat values at the end of the treatment period. There was a statistically significant difference between the C + RSG and C groups in 3-NT levels. In group D, 3-NT and MDA levels were found to be increased when compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels were found to be decreased when compared with C and C + RSG. Our study suggests that the treatment of D rats with RSG for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes-related vascular diseases, RSG treatment may be cardioprotective.     

Ulva rigida improves carbohydrate metabolism, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats

This study was designed to investigate the effects of Ulva rigida, one of the green algae, on the lipid profile and oxidative–antioxidative systems in streptozotocin‐induced diabetic rats. Forty Wistar rats randomly divided into four groups: control (C), control + U. rigida extract (C + URE), diabetes (D) and diabetes + U. rigida extract (D + URE). U. rigida (2%) was administered in drinking water for 5 weeks after the induction of diabetes. U. rigida reduced the blood glucose, serum total cholesterol, triglyceride levels and plasma and tissue malondialdehyde (MDA) levels in the D + URE group. Insulin levels were significantly higher in the D + URE than those of the D group. Serum total cholesterol and tissue MDA levels were reduced in the C + URE group. Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities were higher in the D and C + URE groups compared with the C group. Paraoxonase and arylesterase activities were lower in the D group while U. rigida increased paraoxonase activities in C + URE and D + URE groups. This is the first study which showed U. rigida has antidiabetic and antihyperlipidemic effects and improves oxidative stress in diabetic rats. We conclude that U. rigida might have a potential use as a protective and/or therapeutic agent in diabetes mellitus. Copyright © 2011 John Wiley & Sons, Ltd.     

Oxidative stress in childhood type 1 diabetes: Results from a study covering the first 20 years of evolution

This study aimed to further analyse the potential role of oxidative stress in children and adolescents with type 1 diabetes at clinical onset, during disease progression and when early microvascular complications ( + DC) appeared. Compared with age-matched controls, diabetic patients had greater oxidative damage to lipids, proteins and DNA demonstrated by analysis of plasma and erythrocyte malondialdehyde, carbonyl proteins and leukocyte 8-hydroxy-deoxyguanosine, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma lipid levels were significantly associated with lipid and protein oxidation products. Erythrocyte glutathione and glutathione-peroxidase activity were significantly decreased with the lowest values at onset and in + DC sub-groups. Insulin therapy in the first year improved metabolic and oxidant-antioxidant status and, consequently, hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation, thereby supporting the concept of glucotoxicity and lipotoxicity being inter-related. The overall increase in lipid, protein and DNA oxidative damage in diabetic patients with microangiopathy could be pathogenetically relevant in the early development of diabetes-related complications.     

Oxidative stress in childhood type 1 diabetes: Results from a study covering the first 20 years of evolution

This study aimed to further analyse the potential role of oxidative stress in children and adolescents with type 1 diabetes at clinical onset, during disease progression and when early microvascular complications ( + DC) appeared. Compared with age-matched controls, diabetic patients had greater oxidative damage to lipids, proteins and DNA demonstrated by analysis of plasma and erythrocyte malondialdehyde, carbonyl proteins and leukocyte 8-hydroxy-deoxyguanosine, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma lipid levels were significantly associated with lipid and protein oxidation products. Erythrocyte glutathione and glutathione-peroxidase activity were significantly decreased with the lowest values at onset and in + DC sub-groups. Insulin therapy in the first year improved metabolic and oxidant-antioxidant status and, consequently, hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation, thereby supporting the concept of glucotoxicity and lipotoxicity being inter-related. The overall increase in lipid, protein and DNA oxidative damage in diabetic patients with microangiopathy could be pathogenetically relevant in the early development of diabetes-related complications.     

α-亚麻酸对糖尿病大鼠炎症介质和氧化应激的影响

目的:观察α-亚麻酸(ALA)对糖尿病大鼠体内炎症介质和氧化应激的影响,探讨ALA在糖尿病防治中的作用。方法:雄性SD大鼠高脂饮食喂养4周后,腹腔注射链脲佐菌素(STZ)30 mg/kg建立2型糖尿病(T2DM)模型。将大鼠随机分为3组(n=10):正常对照组、糖尿病模型组和ALA治疗组(500μg/kg.d)。4周后测定大鼠血清中肿瘤坏死因子(TNF-α)、可溶性P-选择素(sP-selectin)、可溶性细胞间黏附分子(sICAM-1)、一氧化氮(NO)、丙二醛(MDA)的含量以及超氧化物岐化酶(SOD)和过氧化氢酶(CAT)的活性。结果:与正常对照组相比,糖尿病大鼠血清中炎症介质TNF-α、sP-selectin和sICAM-1的含量增加,血清NO含量下降而MDA升高,同时抗氧化酶SOD和CAT的活性降低;ALA治疗可显著降低糖尿病大鼠血清中TNF-α、sP-selectin和sICAM-1的含量(与STZ+vehicle组相比,P<0.01),增加血清NO水平并减少MDA含量,升高抗氧化酶SOD和CAT的活性(与STZ+vehicle组相比,均P<0.05)。结论:ALA可显著降低糖尿病大鼠血清炎症介质的生成,减轻氧化应激水平,具有抗炎和抗氧化作用。提示ALA对糖尿病及糖尿病并发症的发生发展可能具有一定的防治作用。     

Oxidative stress and susceptibility to mitochondrial permeability transition precedes the onset of diabetes in autoimmune non-obese diabetic mice

Abstract

Beta cell destruction in type 1 diabetes (TID) is associated with cellular oxidative stress and mitochondrial pathway of cell death. The aim of this study was to determine whether oxidative stress and mitochondrial dysfunction are present in T1D model (non-obese diabetic mouse, NOD) and if they are related to the stages of disease development. NOD mice were studied at three stages: non-diabetic, pre-diabetic, and diabetic and compared with age-matched Balb/c mice. Mitochondria respiration rates measured at phosphorylating and resting states in liver and soleus biopsies and in isolated liver mitochondria were similar in NOD and Balb/c mice at the three disease stages. However, NOD liver mitochondria were more susceptible to calcium-induced mitochondrial permeability transition as determined by cyclosporine-A-sensitive swelling and by decreased calcium retention capacity in all three stages of diabetes development. Mitochondria H₂O₂ production rate was higher in non-diabetic, but unaltered in pre-diabetic and diabetic NOD mice. The global cell reactive oxygen species (ROS), but not specific mitochondria ROS production, was significantly increased in NOD lymphomononuclear and stem cells in all disease stages. In addition, marked elevated rates of 2′,7′-dichlorodihydrofluorescein (H₂DCF) oxidation were observed in pancreatic islets from non-diabetic NOD mice. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and lipidomic approach, we identified oxidized lipid markers in NOD liver mitochondria for each disease stage, most of them being derivatives of diacylglycerols and phospholipids. These results suggest that the cellular oxidative stress precedes the establishment of diabetes and may be the cause of mitochondrial dysfunction that is involved in beta cell death.     

Oxidative stress in silicosis: Evidence for the enhanced clearance of free radicals from whole lungs

We hypothesized that reactive oxygen species (ROS) may be involved in the pathogenesis of silicosis. To investigate ROS' dependent pathophysiological processes during silicosis we studied the kinetic clearance of instilled stable nitroxide radicals (TEMPO). Antioxidant enzymes' superoxide dismutase (SOD) and glutathione peroxidase (GPx), and lipid peroxidation were also studied in whole lungs of rats exposed to crystalline silica (quartz) and sham exposed controls. Low frequency L-band electron spin resonance spectroscopy was used to measure the clearance of TEMPO in whole-rat lungs directly. The clearance of TEMPO followed first order kinetics showing significant differences in the rate for clearance between the diseased and sham exposed control lungs. Comparison of TEMPO clearance rates in the sham exposed controls and silicotic rats showed an oxidative stress in the rats exposed to quartz. Studies on the antioxidant enzymes SOD and GPx in the lungs of silicotic and sham exposed animals supported the oxidative stress and accelerated clearance of TEMPO by up regulated levels of enzymes in quartz exposed animals. Increased lipid peroxidation potential in the silicotics also supported a role for enhanced generation of ROS in the pathogenesis of silica-induced lung injury. These in vivo experiments directly demonstrate, for the first time, that silicotic lungs are in a state of oxidative stress and that increased generation of ROS is associated with enhanced levels of oxidative enzymes and lipid peroxidation. This technique offers great promise for the elucidation of ROS induced lung injury and development of therapeutic strategies for the prevention of damage.     

Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity,type 2 diabetes mellitus and breast cancer

Abstract

Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer.     

Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats

Abstract

The present study was aimed to investigate the effect of D-pinitol on hyperglycaemia mediated oxidative stress by analysing the hepatic antioxidant competence, pro-inflammatory cytokines and ultrastructural changes in liver tissues of streptozotocin-induced diabetic rats. Oral administration of D-pinitol (50 mg/kg b.w.) resulted in significant (p < 0.05) attenuation in blood glucose, glycosylated haemoglobin and pro-inflammatory markers such as TNF-α, IL-1β, IL-6, NF-κB p65 unit and NO and significant (p < 0.05) elevation in the plasma insulin level. In addition, D-pinitol instigated a significant escalation in the levels of hepatic tissue non-enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant (p < 0.05) decrease in lipid peroxides and hydroperoxides formation, thus demonstrating the protective role of D-pinitol on the hepatic tissues from oxidative stress-induced liver damage. These biochemical observations were complemented by histological and ultrastructural examination of liver section. Thus, the present study demonstrates the hepatoprotective nature of D-pinitol by attenuating hyperglycaemia-mediated pro-inflammatory cytokines and oxidative stress.     

Effect of docosahexaenoic acid intake on lipid peroxidation in diabetic rat retina under oxidative stress

Docosahexaenoic acid (DHA) plays an important role in visual function but has a highly oxidation-prone chemical structure. Therefore, we investigated how dietary DHA affects the generation of lipid peroxides in rat retina under oxidative stress in diabetes with/without vitamin E (VE) deficiency. Streptozotocin-induced (50 mg i.p./kg B.W.) diabetic Sprague-Dawley (SD) rats were assigned to four groups: (i) control/VE(+), (ii) DHA/VE(+), (iii) control/VE( - ) and (iv) DHA/VE( - ), and raised for 28 days. We then measured lipid peroxide levels in the retina, serum and liver. With a normal intake of VE, dietary DHA increased only the retinal level of thiobarbituric acid-reactive substances (TBARS) slightly. In contrast, in rats with VE deficiency, dietary DHA increased serum and liver lipid peroxide levels but not in the retina. These results suggest that dietary DHA does not necessarily promote lipid peroxidation in the retina even under high oxidative stress.     

Nrf2 as a target for prevention of age‐related and diabetic cataracts by against oxidative stress

Cataract is one of the most important causes of blindness worldwide, with age‐related cataract being the most common one. Agents preventing cataract formation are urgently required. Substantial evidences point out aggravated oxidative stress as a vital factor for cataract formation. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/Kelch‐like erythroid‐cell‐derived protein with CNC homology (ECH)‐associated protein 1 (Keap1) system is considered as one of the main cellular defense mechanisms against oxidative stresses. This review discusses the role of Nrf2 pathway in the prevention of cataracts and highlights that Nrf2 suppressors may augment oxidative stress of the lens, and Nrf2 inducers may decrease the oxidative stress and prevent the cataract formation. Thus, Nrf2 may serve as a promising therapeutic target for cataract treatment.     

有氧运动和谷氨酰胺对二型糖尿病大鼠氧化应激及相关因子表达的影响

目的:探讨有氧运动和谷氨酰胺(Gln)对二型糖尿病(T2MD)大鼠抗氧化应激及炎性因子的影响。方法:用链脲佐菌素(STZ)诱导糖尿病大鼠模型,将成年雄性SD大鼠50只,6周龄,随机分为5组(n=10):包括安静对照组(N)、糖尿病对照组(D)、糖尿病施加有氧运动组(DE)、糖尿病施加谷氨酰胺组(DG)、糖尿病施加有氧运动+谷氨酰胺组(DEG)。6周后,检测干预后糖尿病大鼠糖脂代谢、抗氧化应激及炎性因子等相关指标,并探讨影响炎症反应的可能机制。结果:与N组相比,D组大鼠血清MDA、血糖、TC、TG、胰岛素、瘦素、TNF-α水平均明显升高(P<0.01),血清中SOD、GSH-Px、脂联素、HDL-C的水平均明显降低(P<0.01);与D组相比,三个干预组血清中MDA、血糖、TC、TG、胰岛素、瘦素、TNF-α水平降低,血清中HDL-C、SOD、GSH-Px、脂联素的水平均明显升高(P<0.05,P<0.01),且两者联合对上述指标的改善作用更为明显(P<0.01)。结论:有氧运动和Gln均能缓解糖尿病大鼠糖脂代谢及紊乱、氧化应激损伤及炎症反应,两者联合对其作用优于单一作用。     

Sirt3-dependent deacetylation of SOD2 plays a protective role against oxidative stress in oocytes from diabetic mice

Maternal diabetes has been demonstrated to adversely affect oocyte quality in mouse oocytes. However, the potential molecular mechanisms are poorly understood. Here, we established a type I diabetic mouse model and detected the increased reactive oxygen species (ROS) levels and decreased Sirt3 expression in oocytes from diabetic mice. Furthermore, we found that forced expression of Sirt3 in diabetic oocytes significantly attenuates such an excessive production of ROS. The acetylation status of lysine 68 of superoxide dismutase (SOD2K68) is dependent on Sirt3 in oocytes. In line with this, SOD2K68 acetylation levels were markedly increased in diabetic oocytes, and Sirt3 overexpression could effectively suppress this tendency. Importantly, the deacetylation-mimetic mutant SOD2K68R is capable of partly preventing the oxidative stress in oocytes from diabetic mice. In conclusion, our findings support a model where Sirt3 plays a protective role against oxidative stress in oocytes exposed to maternal diabetes through deacetylating SOD2K68.     

Antioxidant enzymatic defense in salivary glands of streptozotocin‐induced diabetic rats: a temporal study

Hyperglycemia induces overproduction of superoxide and it is related to diabetic complications. In this study, we analyzed the antioxidant enzymatic defense and the lipid peroxidation of rat salivary glands in six different periods of diabetic condition. Ninety‐six rats were divided into 12 groups: C7/14/21/28/45/60 (non‐diabetic animals) and D7/14/21/28/45/60 (diabetic animals). Diabetes was induced by streptozotocin and the rats were euthanized after 7, 14, 21, 28, 45, or 60 days. Their parotid (PA) and submandibular (SM) glands were removed soon after the sacrifice and the total protein and malondialdehyde (MDA) concentrations, as well as, the superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were determined. Twenty‐one days after the diabetes induction, the SM glands showed an increase in SOD, CAT, and GPx activities, as well as, MDA concentration. Concerning the PA glands, an increase in the CAT activity and MDA content was observed throughout the observation period. The results suggest that diabetes can cause alterations on the salivary glands and that PA and SM glands react differently when exposed to diabetes condition. However, no impairment of antioxidant system was observed in the group whose diabetic condition had been induced 60 days earlier, herein named 60‐day group. Copyright © 2010 John Wiley & Sons, Ltd.     

Protective effect of ganoderic acid against the streptozotocin induced diabetes,inflammation, hyperlipidemia and microbiota imbalance in diabetic rats

Diabetes mellitus (DM) is a metabolic disorder with numerous symptoms categorized via serves hyperglycemia effect along with altered fat, protein and carbohydrate metabolism mainly resultant from defects in insulin action/secretion or both. The aim of the current experimental study was to comfort the neuroprotective effect of ganoderic acid against the streptozotocin (STZ)-induced type I diabetes mellitus in mice and explore the underlying mechanism. Differentiation of 3T3-L1 preadipocytes effect; hepatic and glucose consumption effect of ganoderic acid was estimated on HepG2 cell lines and peroxisome proliferator-activated receptor (PPAR). FFA content was estimated in adipose and hepatic tissues. Ganoderic acid induced the 3T3-L1 preadipocytes differentiation. The mRNA expression of PPAR was increased in the high glucose-treated group in HepG2 and ganoderic acid treatment down-regulated the mRNA expression of PPAR. Ganoderic acid exhibited the inhibitory effect of α-glucosidase and α-amylase. Ganoderic acid demonstrated the reduced blood glucose and increase insulin level and also reduced the free fatty in hepatic and adipose tissue. Histopathological study showed the enhancement of β-cells in ganoderic acid-treated mice. Finally, their prebiotic effects on gut microbiota were illustrated via enhancing the population of diabetes resistant bacteria and also reducing the quantity of diabetes sensitive bacteria. Ganoderic acid attenuated STZ induced T1DM in mice via inflammatory pathways.     

The protective effect of melatonin against cypermethrin-induced oxidative stress damage in Spodoptera litura (Lepidoptera: Noctuidae)

Antioxidant enzymes form the first-line defense against free radicals damage in organisms. Their regulation depends mainly on the oxidant and antioxidant status of the cell, given that oxidants are their principal modulators. Therefore, the aim of the present study was to investigate the effect of melatonin on synthetic pyrethroid insecticide-induced antioxidative enzymes activity in Spodoptera litura larvae. In addition, activities of enzymatic antioxidants viz. superoxide dismutase (SOD), glutathione S-transferase (GST), catalase (CAT), glutathione reductase (GR), α, β-esterase, and acetylcholine esterase (AChE) were assessed. There was no significant change in GST levels in the melatonin-treated groups. Melatonin modulates cypermethrin-induced changes in the activities of esterase and AChE, whereas SOD, CAT, and GR activity was significantly increased in melatonin-treated samples when compared to control. In conclusion, the results of the current study revealed that SP toxicity activated oxidant systems in all antioxidant systems in some tissues of insects. Melatonin administration led to a marked increase in antioxidant activity and inhibited GST and AChE in most of the tissues studied.     

姜黄素及其类似物J7对2型糖尿病大鼠睾丸氧化应激损伤的干预作用*

目的: 研究姜黄素(CUR)及其类似物J7对糖尿病大鼠睾丸氧化应激损伤的干预作用。方法: 60只SD大鼠随机分组,其中10只作为正常(NC)组,余50只通过高脂饮食和腹腔注射链脲佐菌素诱导建立糖尿病大鼠模型,造模成功后将其再分为4组:糖尿病(DM,n=12)组、姜黄素治疗(CUR,n=10)组、J7高剂量治疗(J+,n=10)组、J7低剂量治疗(J-,n=10)组。CUR组大鼠每天予以姜黄素20 mg/kg灌胃治疗,J+及J-组分别予以J7 20 mg/kg、10 mg/kg灌胃治疗,8周后处死大鼠,测量各组大鼠体重、空腹血糖,羟胺法和硫代巴比妥酸法分别检测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,Western blot法检测tNrf2、pNrf2、CAT、NQO1蛋白表达水平,qRT-PCR检测CAT、NQO1、HO1 mRNA表达水平,光镜下观察大鼠睾丸形态学改变,免疫组化检测Nrf2及CAT蛋白表达情况。结果: DM组血糖、MDA水平升高(P＜0.05),体重、SOD活性、pNrf2/tNrf2、CAT、NQO1蛋白及CAT、NQO1、HO1 mRNA水平均有下降(P＜0.05);光镜下见睾丸各级生精细胞减少、排列紊乱;免疫组化显示Nrf2蛋白核周表达量下降,CAT蛋白表达水平降低。经姜黄素及J7治疗后,三个治疗组的MDA水平均下降(P＜0.05),SOD活性、pNrf2/tNrf2、CAT、NQO1蛋白及NQO1、HO1 mRNA水平均上升(P＜0.05),J+及J-组血糖显著下降(P＜0.05),J+组CAT mRNA水平显著上升(P＜0.05);J+组pNrf2/tNrf2比值明显高于CUR组及J-组(P＜0.05),J+组CAT蛋白水平也明显高于J-组(P＜0.05),其余指标在三个治疗组间不具有显著性差异。光镜下见三个治疗组睾丸形态学病变减轻;免疫组化显示Nrf2蛋白核周表达量上升,CAT蛋白表达水平升高。提示高剂量J7抗糖尿病大鼠睾丸的氧化应激损伤的能力较强。结论: 姜黄素及J7可在一定程度上对抗糖尿病大鼠睾丸的氧化应激损伤,其机制可能与Nrf2-ARE信号通路的激活相关。