Tissues Of Streptozotocin-induced Diabetic Rats Research Articles

Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats.

To investigate the stability of the seven housekeeping genes: beta-actin (ActB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18s ribosomal unit 5 (18s), cyclophilin A (CycA), hypoxanthine-guanine phosphoribosyl transferase (HPRT), ribosomal protein large P0 (36B4) and terminal uridylyl transferase 1 (U6) in the diabetic retinal tissue of rat model. The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in two groups; normal control rats and streptozotocin-induced diabetic rats. The stability analysis of gene expression was investigated using geNorm, NormFinder, BestKeeper, and comparative delta-Ct (ΔCt) algorithms. The 36B4 gene was stably expressed in the retinal tissues of normal control animals; however, it was less stable in diabetic retinas. The 18s gene was expressed consistently in both normal control and diabetic rats' retinal tissue. That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats. Furthermore, there was no ideal gene stably expressed for use in all experimental settings. Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.

The study of the effect of biocanin A (a type of isoflavone) on serum levels of tumor necrosis factor alpha, interferon gamma and malondialdehyde and glutathione levels in pancreatic tissue of streptozotocin-induced diabetic rats

The study of the effect of biocanin A (a type of isoflavone) on serum levels of tumor necrosis factor alpha, interferon gamma and malondialdehyde and glutathione levels in pancreatic tissue of streptozotocin-induced diabetic rats

Retraction note: Effect of probucol on autophagy and apoptosis in the penile tissue of streptozotocin-induced diabetic rats.

[This corrects the article DOI: 10.4103/aja.aja_89_19].

Effects of Cinnamon Extract Consumption and Swimming Exercise on the Expression of ATGL and CGI-58 in the Visceral Adipose Tissue of Streptozotocin-induced Diabetic Rats

Introduction: Diabetes is a widespread disease, and various techniques are used for its prevention, control, and treatment, including physical exercises and medicinal herbs. Natural medicines and exercise are comparatively inexpensive and cause fewer complications compared to chemical drugs. The present study aimed to evaluate the effects of a swimming course and cinnamon extract consumption on the expression of adipose triglyceride lipase and CGI-58 in the visceral adipose tissue of streptozotocin-induced diabetic rats. Methods: This experimental study was conducted on 28 diabetic rats, which were randomly divided into four groups of seven, including 1) control (C),2) cinnamon use (Ci),3) swimming course(S), and 4) cinnamon extract with swimming (S+Ci). The animals received the intended treatment for six weeks in packs of three and four and five classes per week, while the rats in groups two and four received 200mg/kg of cinnamon orally every day for six weeks. Data analysis was performed using the one-way analysis of variance (ANOVA) and Tukey�s post-hoc test at the significance level of P�0.050. Results: The results of ANOVA indicated that ATGL gene expression in the S (P=0.04) and S+Ci groups (P=0.0001) was significantly higher than the control group. In addition, ATGL gene expression in the S group (P=0.0006) was higher compared to the Ci group, while it was significantly higher in the S+Ci group (P=0.0001) compared to the Ci and S groups. CGI-58 gene expression in the S+Ci group (P=0.0001) was also significantly higher than the control, S, and Ci groups, while it was significantly higher in the S group (P=0.036) compared to the Ci group. Conclusion: According to the results, swimming exercise and cinnamon extract consumption increased the expression of CGI-58 and ATGL protein in the diabetic rats. Therefore, it seems that CGI-58 plays a key role in the activation of lipolysis by ATGL, and higher CGI-58 could increase ATGL, which ultimately accelerates the lipolysis process, reduces fat, and improves insulin resistance in the visceral adipose tissue.

Antiapoptotic and antioxidative effects of cerium oxide nanoparticles on the testicular tissues of streptozotocin-induced diabetic rats: An experimental study.

BackgroundCerium dioxide nanoparticles (CNPs) due to the antidiabetic and antioxidant activities are proposed for the treatment of oxidative stress-associated diseases.ObjectiveTo examine the impact of CNPs on hyperglycemia-induced apoptosis and oxidative stress in the testis of diabetic rats.Materials and MethodsTwenty-four male rats were divided into four groups (n = 6/each) as diabetic rats, CNPs group, diabetic + CNPs rats, and controls. The control group was fed only mouse food and water. Rats became diabetic through receiving streptozotocin (STZ) 60 mg/kg. CNPs were given to the rats at a dose of 30 mg/kg daily for 2 wk. Malondialdehyde and total thiol group (TTG) levels were measured using spectrofluorometer. Expression of b-cell lymphoma protein 2-associated X protein (BAX) and b-cell lymphoma protein 2 (Bcl-2) were investigated using quantitative real-time polymerase chain reaction. Western blot analysis was used to examine caspase 3 protein levels.ResultsThe content of malondialdehyde significantly increased in the STZ-diabetic rats, while TTG levels demonstrated a remarkable decrease. Caspase-3, BAX, and BAX/Bcl-2 mRNA ratio raised significantly in the STZ-diabetic rats. On the other hand, Bcl-2 mRNA levels reduced in the testis of diabetic rats (p = 0.006). Intervention with CNPs caused a substantial increase in the TTG levels, while the malondialdehyde contents, caspase-3, BAX levels, as well as BAX/Bcl-2 mRNA ratio were considerably decreased following CNPs treatment. Administration of CNPs increased mRNA levels of Bcl-2 (p 0.0001).ConclusionCNPs treatment attenuates testicular apoptosis and oxidative stress induced by diabetes. This nanoparticle might be suggested for the treatment of diabetes-associated reproductive disorders.

Antioxidant and anti-inflammatory effect of olive leaf extract treatment in diabetic rat brain.

Olive (Olea europaea L.) plays a promising role in pharmaceutical, nutraceutical, and cosmetic production. On the other hand, olive leaf is widely used in folk medicine due to its antihyperglycemic activity. For this aim, possible effects of olive leaf extract (OLE) in the brain tissue of streptozotocin-induced diabetic rats were investigated. A total of 28 male rats were divided into four equal groups as control, diabetic (single dose of 45mg/kg streptozotocin, i.p.), OLE (500mg/kg/day), and diabetic+OLE groups. The study was terminated 21days after the diabetes model was formed. At the end of the study, all the animals were sacrificed and blood and brain tissues were isolated. Relative brain weights, complete blood count, blood glycated hemoglobin, serum glucose, total protein, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, insulin, gonadal hormone levels, production and messenger ribonucleic acid(mRNA) levels of proinflammatory cytokines and mediators, total thiol, total oxidative stress, and total antioxidant status levels and fatty acid composition in brain tissue were measured in all study groups. In diabetic rats, relative brain weight and serum insulin level decreased, glycated hemoglobin, oxidative stress, production and mRNA level of proinflammatory cytokines and mediators increased, hyperglycemia, hypercholesterolemia and hypertriglyceridemia, degraded fatty acid composition, anemia, leukopenia, and thrombocytopenia occurred. After OLE treatment, a remarkable improvement in most of these parameters, except gonadal hormones, has been observed in diabetic rats. This study suggests that olive leaf can be a precious neuroprotective agent in diabetes.

Effects of Eight Weeks of Combined Training with Antioxidant Vitamins E and C on Glutathione, Glutathione Peroxidase, and Superoxide Dismutase in the Heart Tissue of Streptozotocin-induced Diabetic Rats

Background: Diabetes leads to metabolic disorders in the heart by creating free radicals and compromising the antioxidant defense system. Objectives: The aim of this study was to investigate the effect of eight weeks of combined training and supplementation with antioxidant vitamins E and C on the antioxidant capacity of heart tissue in streptozotocin-induced diabetic rats. Methods: Sixty male Sprague Dawley rats (weight: 280 ± 20 g; age: 2-3.5 months) were randomly divided into five groups as follows: (1) healthy control, (2) diabetic control, (3) diabetic + combined training, (4) diabetic + supplementation, and (5) diabetic + combined training + supplementation. The combined training protocol included incremental resistance training of 5 - 45% of rat weight on the ladder, and incremental endurance training was performed for 10 - 30 minutes at an intensity of 40 - 75% of maximum speed on the treadmill during eight weeks. The heart tissue was extracted and antioxidant enzymes were measured by lab spectroscopy 48 hours after the last training session. Data was analyzed using independent samples t-test, two-way ANOVA, and Bonferroni test (P ≤ 0.05). Results: The induction of diabetes significantly reduced glutathione (GSH; P = 0.001), glutathione peroxidase (GPx; P = 0.004), and superoxide dismutase (SOD; P = 0.001). In the treatment groups, a significant increase in the effect size of GSH (in the training and supplementation group: 6.45, training group: 3.18, and supplementation group: 2.92), GPX (in the training and supplementation group: 0.03, supplementation group: 0.023, and training group: 0.021), and SOD (in the training and supplementation group: 556.68, training group: 405.70, and supplementation group: 401.46 nmol / mL) was observed. Conclusions: Antioxidant supplementation and training by reducing the harmful effects of hyperglycemia strengthen the antioxidant defense system of heart tissue, and the combination of the two interventions is more effective than either alone.

Effects of curcumin administration on Nesfatin-1 levels in blood, brain and fat tissues of diabetic rats.

We evaluated the efficacy of curcumin administration on blood glucose levels and its relationship with nesfatin-1 levels in blood brain and adipose tissue of streptozotocin-induced diabetic rats. A total of 28 male rats were divided into four groups: control group, type 2 diabetes mellitus (DM) group, control plus curcumin group and type 2DM plus curcumin group. After fifteen days, blood samples were collected from sacrificed rats. Nesftain-1 levels were analysed from blood, brain, and fat tissues of rats in all groups. Nesfatin-1 level was found to be significantly lower in blood, brain and fat tissues of type 2 DM rats compared to the control group. A significant decrease in fasting blood glucose levels was observed in the curcumin administration group compared to type 2 DM group. Improvement of fasting blood glucose level was accompanied by improvement of nesfatin-1 levels in blood, brain, and fat tissues. As expected, curcumin administration caused significant improvement in fasting blood glucose levels. However, for the first time, we found marked improvements in nesfatin-1 levels in blood, brain, and fat tissues of type 2 DM rats. Thus, considering the crucial role of nesfatin-1 in regulation of glucose metabolism, it is logical to expect an interactive relationship between curcumin and nesfatin-1.

Effect of Fucoidan on the Regulation of Antioxidant Enzymes in Hepatorenal Tissues of Streptozotocin-Induced Diabetic Rats

Accumulation of reactive oxygen species resulting from hyperglycemia and inadequate endogenous antioxidants are responsible for the complications of diabetes. Accumulation of reactive oxygen species in the cells stimulates apoptosis, which hampers the cell architecture and functions of vital organs. This study investigates the effect of fucoidan from Sargassum wightii, a potent antioxidant with a regulatory effect on blood glucose homeostasis, in the liver and kidney of diabetic rats. Diabetes was induced in rats by administrating streptozotocin 50 mg/kg for 3 consecutive days through intraperitoneal injection. 30 male Wistar rats were divided into five groups consisting of six animals in each group and they were Group A: Control group, Group B: Diabetic group, Group C: Diabetic rats treated with metformin hydrochloride 250 mg/kg, Group D: Diabetic rats treated with fucoidan 50 mg/kg, and Group E: Diabetic rats treated with fucoidan 100 mg/kg. Fucoidan was administrated orally for 4 w after the induction of diabetes. Superoxide dismutase activity was low in the liver of the diabetic group and it showed 58.5 % activity, compared with the control group. Fucoidan administration elevated superoxide dismutase and it was 66.5 % and 80.6 % respectively in fucoidan 50 mg/kg and fucoidan 100 mg/kg groups, compared with the control group while in the metformin group 93.4 % activity was seen. A similar variation in the superoxide dismutase was observed in the kidney; wherein, administration of fucoidan restored the superoxide dismutase activity and it was 62.9 % in the fucoidan 50 mg/kg group and 79.5 % in the fucoidan 100 mg/kg group, compared with the control group while in diabetic group 49.4 % and metformin group 94.2 % activity were observed. The other tested antioxidant enzymes such as catalase, glutathione peroxidase and glutathione S transferase also showed marked regain in a dose-dependent manner upon administration of fucoidan. This study inferred that the administration of fucoidan in streptozotocininduced diabetic rats improved the antioxidant enzyme activity by moderating the accumulation of reactive oxygen species and reduced the pathophysiology.

Crocin Improves Oxidative Stress in Testicular Tissues of Streptozotocin-Induced Diabetic Rats.

Crocin has been shown to have potent antioxidant properties, but its potential antioxidative effects on testicular tissue during uncontrolled diabetes is unknown. Wistar rats were randomly divided into four separate groups; normal, normal-treated, diabetic and diabetic treated (n=6 per group). Diabetes was induced by a single intravenous injection of streptozotocin (45mg/kg). Two treated groups of animals (diabetic and non-diabetic) received Crocin daily for 56days (40mg/kg/intraperitoneally). At the end of the 56th day, animals were sacrificed and blood and testicular tissue obtained. The level of nitrate, malondialdehyde, glutathione, and the activities of superoxide dismutase and catalase enzymes were determined. Crocin therapy moderated the increased oxidative stress in testicular tissue induced by diabetes with a significant reduction in nitrate and malondialdehyde, whilst reducing superoxide dismutase and catalase enzyme activities in diabetes (p<0.001), though glutathione was unaffected. Treatment by Crocin in normal rats also modestly improved parameters of oxidative stress (p<0.05). Crocin has a protective effect on diabetes induced oxidative stress in testicular tissue in an animal model, though it is unclear if this is a direct antioxidant effect.

Effect of Aerobic Training and Berberine Chloride Supplementation on Oxidative Stress Indices in the Heart Tissue of Streptozotocin-Induced Diabetic Rats

Effect of Aerobic Training and Berberine Chloride Supplementation on Oxidative Stress Indices in the Heart Tissue of Streptozotocin-Induced Diabetic Rats

Phytochemical Analysis of Paliurus spina-christi Fruit and Its Effects on Oxidative Stress and Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rats.

Oxidative stress can play an important role in the autoxidation of glucose, glycation of proteins and activation of polyol metabolism, and the development of various complications in diabetes. This study investigated the protective effect of Paliurus spina-christi (PSC) fruit against diabetes-induced pathologies such as inflammation caused by oxidative stress and its phytochemical content. The bioactive compounds of Paliurus spina-christi fruit extract (PSC-FE) prepared by the infusion method were determined by LC-MS/MS analysis, and the metal reduction and radical removal activity were determined in vitro by DPPH, ABTS, FRAP and CUPRAC methods. The effect of PSC-FE on catalase and superoxide dismutase enzymes and lipid peroxidation in streptozotocin-induced diabetic rat tissues was determined in vivo. For determining in vivo antioxidant activity, the study was carried out on 30 Wistar albino male rats that were distributed into 3 research and 2 control groups. As a result of LC-MS/MS analysis, malic acid (28,424.18 ± 3.21μg/g PSC-FE) and rutin (23,459.68 ± 3.73μg/g PSC-FE) are the highest among the 22 phenolic compounds. The PSC fruit water extracts were determined to have a more powerful antioxidant activity than standard antioxidants. In those groups that received PSC-FE, catalase and superoxide dismutase enzyme levels that decreased in patient group were found to have a statistically meaningful increase in treatment groups (P < 0.01). Although malondialdehyde amount, the last product of lipid peroxidation, was observed to have a statistically meaningful increase in patient group when compared with control group, this increase was decreased in all treatment groups in a statistically meaningful manner (P < 0.01). The PSC was seen to be more successful, when compared with standard antioxidants. The PSC-FE was found to have a rich phenolic diversity. It can be said that the PSC may have a significant therapeutic effect on diabetes caused by oxidative stress due to its biological activities and content.

Antidiabetic and protective effects of Scrophularia striata ethanolic extract on diabetic nephropathy via suppression of RAGE and S100A8 expression in kidney tissues of streptozotocin-induced diabetic rats.

Background The present study was conducted to examine the antidiabetic effects of Scrophularia striata ethanolic extract and to evaluate its effects on oxidative stress markers and RAGE and S100A8 gene expressions in the kidney of type 1 diabetic rats. Methods A total of 36 rats (weight 200-250 g) were randomly assigned into six groups as follows: Cnt, Cnt + S. striata 100, and Cnt + S. striata 200 that received normal saline, 100 mg/kg bw, and 200 mg/kg bw of ethanol extract of S. striata, respectively; and group Dibt, Dibt + S. striata 100, and Dibt + S. striata 200 that received normal saline, 100 mg/kg bw, and 200 mg/kg bw of ethanol extract of S. striata, respectively. Type 1 diabetes was induced in rats by a single injection of streptozotocin (55 mg/kg bw). After 60 days of treatment, biochemical factors and oxidative stress markers (superoxide dismutase [SOD] and malondialdehyde [MDA]) were measured using spectrophotometric methods. RAGE and S100A8 gene expressions were analyzed using real-time polymerase chain reaction. Results Diabetes significantly impairs serum and urine fasting blood glucose (FBG), lipid profile, creatinine, urea, and albumin parameters. After the treatment with S. striata extract, these parameters are close to the normal range. It was shown that the S. striata extract significantly decreased the kidney expression levels of RAGE and S100A8 genes and improved oxidative stress markers (SOD and MDA) in the kidney tissues when compared with the diabetic control group. It was also found that the beneficial effects of the S. striata were dose dependent. Conclusions The ethanolic extract of S. striata has beneficial antidiabetic effects. Moreover, by reducing RAGE and S100A8 gene expressions and by improving oxidative stress, S. striata might be used as adjuvant treatment for diabetic complications.

The Influence of Metformin to the Transcriptional Activity of the mTOR and FOX3 Genes in Parapancreatic Adipose Tissue of Streptozotocin-Induced Diabetic Rats.

The mammalian target of rapamycin is not only a central regulator of lipid metabolism that controls the processes of adipogenesis and lipolysis but also a regulator of the immunometabolism of immune cells that infiltrate adipose tissue. In turn, the level of progression of diabetes is significantly influenced by the Treg subpopulation, the complexity and heterogeneity of which is confirmed by the detection of numerous tissue-specific Tregs, including the so-called VAT Tregs (visceral adipose tissue CD4+Foxp3+ regulatory T cells). Therefore, the purpose of the study was to determine the mRNA expression levels of mTOR, Foxp3, IL1β, and IL17A genes in rat parapancreatic adipose tissue with experimental streptozotocin-induced diabetes mellitus, with or without metformin administration. The experiments were performed on male Wistar rats with induced diabetes as a result of streptozotocin administration. Molecular genetic studies were performed using real-time reverse transcription-polymerase chain reaction. The development of diabetes caused transcriptional activation of the mammalian target of rapamycin protein kinase gene, as well as increased mRNA expression of the pro-inflammatory cytokines IL1β and IL17A, but did not affect Foxp3 mRNA expression. The intervention with metformin in diabetic rats inhibited the mammalian target of rapamycin mRNA expression and caused an increase in the transcriptional activity of the Foxp3 gene in parapancreatic adipose tissue.

Concise anti-oxidative stress defence effects of Duvalia corderoyi in the liver and kidney tissues of streptozotocin-induced diabetic rats

ABSTRACT The aim of the study was to evaluate the effect of Duvalia corderoyi (D. corderoyi) extracts in oxidative stress status and histopathology of liver and kidney tissues in streptozotocin (STZ)-induced diabetic rats. Fifty male Wistar albino rats were injected intraperitoneally (IP) with STZ. Rats with fasting blood glucose levels of 250 mg/dl and above were considered diabetic. Rats were subsequently fed orally with D. corderoyi extracts (100,200 mg/kg bw) for 30 days. Fasting blood glucose, insulin, and oxidative status in liver and kidney tissues were measured and histopathological analysis was performed. The blood glucose and malondialdehyde levels were decreased and the insulin, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase levels were increased in D. corderoyi treated diabetic rats in comparison to those in untreated diabetic rats. Moreover, D. corderoyi relieved the injury in liver and kidney tissues of treated diabetic rats. Administration of D. corderoyi led to significant ameliorative effects on the oxidative stress and histopathology of liver and kidney tissues of D. corderoyi treated diabetic rats.

Effect of Crocin on Bax, Bcl-2, and Oxidative Stress Markers in the Testis Tissue of Streptozotocin-Induced Diabetic Rats

Aims Type 1 diabetes is a high-prevalent endocrine disease and causes oxidative stress in the testis tissue. In the treatment of diabetes, the tendency toward herbal medicines use is increasing. This study aimed to investigate the crocin effect on the Bax, Bcl2 (B-cell lymphoma 2), and anti-oxidant levels of streptozotocin-induced diabetic rats. Methods &amp; Materials This experimental study was performed at Payam Noor University. In total, 24 rats were divided into 4 groups, as follows: control, untreated diabetic, and 2 crocin-treated (50, 100 mg/mL, 25 days intraperitoneal injection) diabetic groups. The diabetic groups were diabetic rats receiving the Intraperitoneal (IP) injection of Streptozotocin (STZ). On day 25, the testicles were dissected to evaluate antioxidant enzymes, Bax and Bcl2. The obtained results were analyzed in SPSS using one-way Analysis of Variance (ANOVA) and Least Significant Difference (LSD) test. Findings The pro-apoptotic Bax and malondialdehyde levels in the treated group with a concentration of 100 mg/mL of crocin was significantly reduced, compared to the treated group with a concentration of 50 mg/mL of crocin and the control group. However, the level of pro-apoptotic Bcl-2 and glutathione peroxidase, superoxide dismutase, and catalase enzymes in the treated group with a concentration of 100 mg/mL of crocin significantly increased, compared to the treated group with a concentration of 50 mg/mL of crocin, and the control group (P&lt;0.05). Such finding indicates the effect of crocin concentration. Additionally, crosin significantly reduced the glucose level in diabetic rats. Conclusion Crocin improved the antioxidant indicators and diabetes-induced damages in the testis tissue of diabetic rats.

Effect of probucol on autophagy and apoptosis in the penile tissue of streptozotocin-induced diabetic rats.

Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction (DMED). Probucol is considered to have anti-apoptotic effects, but its relationship with autophagy has not been reported. The aim of this study was to investigate the effects and mechanisms of probucol on erectile function. Thirty Sprague–Dawley (SD) male rats (12 weeks old) were fasted for 12 h. Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg−1 streptozotocin (STZ). Ten rats were given vehicle only and used as a sham group. After 72 h, 20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l−1 were used as successfully established diabetic rats. The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg−1 for 12 weeks. After treatment, the intracavernous pressure (ICP) was used to measure erectile function upon electrical stimulation of the cavernous nerve. After euthanasia, penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), microtubule-associated protein light chain 3-II (LC3-II), mammalian target of rapamycin (mTOR), and sequestosome 1 (P62). Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit. After 12 weeks of treatment, the erectile function of the probucol group was significantly better than that of the DM group (P < 0.05). Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group (all P < 0.05), while Bcl-2, mTOR, and P62 protein expression levels were significantly higher than those in the DM group (all P < 0.05). We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.

Effect of curcuma on zinc, lipid profile and antioxidants levels in blood and tissue of streptozotocin-induced diabetic rats fed zinc deficiency diet

Due to the importance of zinc as an antioxidant and its crucial role in insulin synthesis, its deficiency may affect adversely diabetic state. So, this study aimed to modulate these effects using Curcuma longa as natural antioxidant. Rats were divided into four groups: two groups fed a zinc sufficient diet one non-diabetic and the other diabetic, while the others two groups diabetic rats fed a zinc-deficient diet, one non-treated group and the other treated with curcuma 1% diet. After four weeks of dietary manipulation, fasting animals were scarified. Zinc deficiency decreased body weight, insulin, zinc tissues, alkaline phosphatase, reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase. Conversely glucose, lipids profile, transaminases and malondialdehyde were increased. However, the above-mentioned parameters were significantly improved following curcuma supplementation. So it seems that curcuma is a potent factor for reducing the oxidative severity of zinc deficiency in experimental diabetes through its antioxidants actions.

Streptozotosin ile Diyabet Oluşturulmuş ve Metformin ile İnsülin Uygulanan Ratlarda Oleuropein'in Çeşitli Dokularda Nitrik Oksit, Glutatyon, Malondialdehit Düzeyleri ve Glutatyon Peroksidaz Aktivitesi Üzerine Etkileri

Objective: The aim of the present study was to investigate the effects of oleuropein on nitric oxide (NO) and oxidant-antioxidant levels in tissues of streptozotocin-induced diabetic rats treated with metformin and insulin. Material and Methods: A total of 40 male Sprague-Dawley rats were used in this study. Animals were divided into 5 groups (n=8) including 3 experiment and 2 control groups. Saline solution was injected intraperitoneally (IP) to the rats in control group. 50 mg/kg STZ was given IP to the Diabetic Control, 50 mg/kg streptozotocin (STZ)+100 mg/kg Metformin+4 IU/kg insulin was given IP to Group 1, 50 mg/kg STZ+100 mg/kg Metformin+4 IU/kg insulin was given IP and 30 mg/kg oleuropein was given orally to Group 2 and 50 mg/kg STZ IP and 30 mg/kg oleuropein was given orally to Group 3. Results: Metformin and insulin with oleuropein have a synergistic effect on regulatory activity of the GSH, MDA, NO levels and GSHPx activities of the kidney, brain and heart tissues. Using metformin and insulin with oleuropein increased the GSH levels of the kidney (p<0.001), brain (p<0.001) and heart tissues (p<0.05); also increased the GSHPx activity of the brain (p<0.01) and the heart tissues (p<0.001) and reduced MDA and NO levels of the kidney, brain and heart tissues (p<0.001). There were no statistically significant differences in GSHPx activity of kidney tissues of experimental groups. Conclusion: Using oleuropein, on streptozotocin-diabetics, in combination with metformin and insulin seems to have synergistic effect on the antioxidants in kidney, brain and heart tissues and effective in regulating the NO level on tissues.

The potential role of melatonin on bone marrow mesenchymal stem cells therapy in pancreatic tissue of streptozotocin-induced diabetic rats.

The present study was established to investigate the role of bone marrow mesenchymal stem cells (MSCs) and melatonin (MT), alone or in combination with each other for improvement of beta cell functions in STZ-induced diabetic rat model. Also, to evaluate the role of melatonin in increasing the efficacy of MSCs. Fifty two male albino rats (130-150g) were divided into six groups. Control: received phosphate buffer saline PBS; Melatonin group received melatonin (10 mg/kg b.wt. day for 2 months by oral intubation); Diabetic untreated group; Diabetic group treated with melatonin; Diabetic group treated with mesenchymal stem cells (MSCs) (A single intravenous injection of 3×106 cell in PBS )and Diabetic group treated with both stem cells and melatonin. Diabetes was induced by a single i.p. injection of 45mg/kg b.wt. of streptozotocin. The results showed that treatment of diabetic rats with either MSCs alone or in combination with melatonin resulted in an increase in body weight and pancreas weight. The biochemical analysis showed significant improvement in glucose, insulin, total antioxidant and malondialdehyde level in diabetic rats treated with either MSCs alone or in combination with melatonin. On the other hand, the results of imumuno-histochemical analysis showed that MSCs and/or melatonin treatment reduced the rate of inflammation and apoptosis of the Islet cells of pancreases as well as increased the rate of pancreatic cell division. Such results were indicated by a significant improvement in the level of TNF-α, IL-10, PCNA, and caspase-3 to levels very close to the control. The microscopic examination of Langerhans islands showed that treatment with MSCs either alone or in combination with melatonin resulted in an improvement in the tissue of the pancreas and reduced number of damaged beta cells. It can be concluded that stem cell therapy has a significant role in restoring the structural and functional efficiency of beta cells in the pancreas. The results also showed that co- treatment of stem cells and melatonin was more effective than stem cell alone. Such result may be due to the role of melatonin as an antioxidant in increasing the efficiency and vitality of stem cells.