Oxidative Stress In Diabetes Research Articles

Streptozotosin ile İndüklenmiş Diyabetik Sıçanlarda Melatoninin Antioksidan Aktivitesi; Kan ve Karaciğer Dokusunda

OBJECTIVE: In this study, it was aimed to investigate the antioxidant protective effect of melatonin supplementation against oxidative damage in blood and liver tissues of rats with experimental type 1 diabetes with Streptozotocin (STZ). MATERIALS AND METHODS: Forty adult Spraque Dawley male rats; Group 1-Control group, Group 2-diabetes group, Group 3- melatonin supplement group and Group 4- diabetes and melatonin supplement group were divided into four groups. Diabetes was induced in rats by administering a single dose of 60 mg / kg STZ intraperitoneally. Melatonin supplementation was administered at a dose of 10 mg / kg / day subcutaneously for 6 weeks. Glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) levels were measured spectrophotometrically in the liver and serum samples taken at the end of the experiment. RESULTS: The results of the study showed that MDA levels increased in the serum and liver tissues of diabetic animals. It was observed that melatonin administration decreased MDA levels in both tissues, increased GSH and CAT levels or kept them stable by preventing it from falling (p <0.05). CONCLUSION: The results of this study are consistent with the consensus that emphasizes and accepts that one of the main causes of complications of diabetes is oxidative stress. Our results show that melatonin has an ameliorating effect on increased oxidative stress in diabetes and melatonin can be used as a therapeutic agent.

ISCHEMIA MODIFIED ALBUMIN AMONG TYPE 2 DIABETIC PATIENTS VISITING A TERTIARY CARE CENTER OF KATHMANDU

Background: Chronic hyperglycemia in diabetes may increase oxidative stress causing ischemia and long-term complications of diabetes. It may also alter albumin, increasing the concentration of serum ischemia modified albumin. The present study was conducted to estimate serum isch­emia modified albumin level and to assess its relationship with parameters of glycemic control in diabetic patients. Methods: In this study, 130 type 2 diabetic patients were enrolled and blood samples were ana­lyzed for ischemia modified albumin, glycated hemoglobin, fasting and postprandial blood glu­cose. Parameters of glycemic control were estimated using routine standard methods and serum ischemia modified albumin was measured manually by spectrophotometric cobalt-albumin bind­ing assay. Participants with glycated hemoglobin level less than 7% were labeled as group 1 and participants with glycated hemoglobin value more than or equal to 7% were labeled as group 2. Results: Group 2 participants had significantly higher mean serum ischemia modified albumin as compared to group 1 (p&lt;0.001). There was significant positive correlation between ischemia modi­fied albumin and parameters of glycemic control; glycated hemoglobin (r=0.300, p=0.001), fasting blood glucose (r=0.239, p=0.006), postprandial blood glucose (r=0.318, p&lt;0.001). However the relationship of ischemia modified albumin with age, body mass index and duration of diabetes were statistically insignificant. Conclusions: The present study shows increase in serum ischemia modified albumin with increase in all three glycemic parameters. This finding suggests that ischemia modified albumin can be used as a marker of hyperglycemia induced oxidative stress in diabetes.

Triphala Ameliorates Nephropathy via Inhibition of TGF-β1 and Oxidative Stress in Diabetic Rats

Introduction: Advanced glycation end products, oxidative stress, and TGF-β expression play a crucial role in pathophysiology of diabetic nephropathy. Inhibition of oxidative stress and TGF-β expression by natural traditional medicines may give an economic and safe alternative treatment option. Triphala churna, a traditional medicine, has been proved to have potent antioxidant activity, and individual components of it have shown significant antidiabetic activity. Hence, the present study was designed to study the effect of Triphala churna in diabetic nephropathy in rats. Methods: Diabetes was induced in rats by administration of streptozotocin (55 mg/kg i.p.). Four weeks after induction of diabetes, the animals were treated with Triphala churna at the doses of 250, 500, and 1,000 mg/kg for next 4 weeks. Various biochemical and urine parameters such as glucose, creatinine, blood urea nitrogen (BUN), total protein, and albumin were assessed at the end of study. Creatinine clearance, BUN clearance, and glomerular filtration rate were determined. Oxidative stress parameters such as malondialdehyde, catalase, reduced glutathione, and superoxide dismutase were determined in kidney tissues. TGF-β1 expression was measured with ELISA, immunohistochemistry, and western blot techniques. Histopathology study was carried out with haemotoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining to determine histological changes. Results: Treatment with Triphala churna significantly improved urine parameters. Triphala churna treatment also improved plasma proteins, albumin, creatinine, and BUN levels. The oxidative stress was reduced in the kidney with the treatment of Triphala churna. Histopathological studies revealed that Triphala churna reduced kidney damage. Immunohistochemistry, ELISA, and western blotting study revealed that treatment with Triphala decreased the expression of TGF-β in kidney tissues. Conclusion: From the results, it can be concluded that Triphala churna has a significant nephroprotective effect because of its capability of inhibiting oxidative stress and TGF-β in diabetes.

Effect of endurance exercise on oxidative stress marker malondialdehyde in type 2 diabetic mice.

Diabetes is associated with oxidative stress and has a significant role in the pathophysiology of the disease and its complications. Exercise training is a powerful therapeutic approach in diabetes and has protective effects against the progress of its complications. Objectives: The aim of this study was to investigate the effect of an endurance exercise program on the oxidative stress marker malondialdehyde (MDA) in high fat diet-low dose streptozotocin induced type 2 diabetic mouse model. Study Design: Randomized Control trial. Setting: Department of Physiology, Akhtar Saeed Medical and Dental College, Lahore. Period: August 2017 to August 2018. Material &amp; Methods: 60 male albino mice were fed a high fat diet containing 60% kCal as fat for 4 weeks. This was followed by intra peritoneal injection of 40mg/kg body weight streptozotocin, given on three consecutive days. Mice with fasting blood glucose more than 250mg/dl after a week were considered diabetic. Half the mice underwent an exercise program which comprised of a 20 minute swimming session per day, with a 6% body weight load attached to the tail of mice, 3 days a week, for 4 weeks. The level of MDA was estimated in both groups using TBARs method. Results: Mean malondialdehyde level was significantly (p˂0.05) reduced in diabetic mice that underwent endurance exercise training. Conclusion: This study highlights the important role of endurance exercise in reducing oxidative stress in diabetes.

159-OR: Vitamin E Treatment Reduces Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias in Type 1 Diabetic Rats

Severe hypoglycemia can lead to fatal cardiac arrhythmias. Our studies have shown that diabetes, per se, increases the risk of hypoglycemia-induced mortality in rats. It was hypothesized that excess oxidative stress, associated with diabetes, increases the heart’s susceptibility to hypoglycemia-induced fatal arrhythmias. To test this hypothesis, Sprague Dawley rats were made diabetic (streptozotocin 65 mg/kg) and randomized to two treatment groups: 1) antioxidant Vitamin E (400 mg/kg/day; n=18) or 2) control (vehicle, n=16) injected subcutaneously over 8 days. Then, rats underwent hyperinsulinemic (0.4 units/kg/min) severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with continuous electrocardiogram recording. Confirming its antioxidant properties, Vitamin E treatment significantly reduced oxidative stress in the heart 3.3-fold versus controls (Figure). As compared to hypoglycemia-induced mortality of 38% in controls, Vitamin E treatment significantly reduced mortality to 6% (p&amp;lt;0.05; Figure). Additionally, Vitamin E treatment reduced 3rd degree heart block (6%) vs. control (46%; Figure). Overall, these results suggest that 1) oxidative stress in diabetes increases the heart’s susceptibility to hypoglycemia-induced arrhythmias, and 2) Vitamin E treatment reduces oxidative stress and reduces both cardiac arrhythmias and mortality to insulin-induced severe hypoglycemia. Disclosure C.M. Reno: None. M.B. Oxspring: None. J. Bayles: None. I. Holiday: None. Y. Huang: None. S.J. Fisher: None. Funding National Institutes of Health (5T32DK091317, R01NS070235); JDRF (3-APF-2017-407-A-N)

Antioxidative and Hypoglycemic Effect of Ta-ermi Extracts on Streptozotocin-Induced Diabetes.

IntroductionThe purpose of the present study was to reveal the potential positive effect of the Ta-ermi extracts on oxidative stress and streptozotocin (STZ)-diabetic mice and rats treated with Ta-ermi water- and alcohol-extracts.MethodsThe study was carried out using three experimental model: 1) in vitro experiments whereby Ta-ermi extracts were incubated with free radical generators such as 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) to evaluate Ta-ermi’s antioxidant effects; 2) testing the hypoglycemic effects of Ta-ermi extracts in streptozotocin (STZ)-induced diabetic mice; and 3) testing the beneficial effects of Ta-ermi extracts on mitochondrial complex I function using STZ-diabetic rats.ResultsIn vitro antioxidant experiments showed that both of the extracts could scavenge free radicals and exhibited inhibitory effects on glucosidase and aldose reductase with differential effects between water extract and alcohol extract. In the STZ mouse diabetic model, both the water- and alcohol-extracts attenuated body weight decrease, decreased blood glucose levels in a concentration-dependent manner, improved insulin sensitivity, and increased oral glucose tolerance ability. In the STZ-diabetic rat model, both the water- and alcohol-extracts were found to be able to lower blood glucose levels in the diabetic animals with no effects on body weight changes. Moreover, in the STZ-diabetic rats, both the water- and alcohol-extracts of Ta-ermi could inhibit the increase of mitochondrial NADH/ubiquinone oxidoreductase (complex I) activity in the pancreas and enhanced complex I activity in the liver but showed no effect on lung or kidney mitochondrial complex I.DiscussionThe present study points to the potential medicinal value of Ta-ermi’s water and alcohol extracts in lowering blood glucose and decreasing diabetic oxidative stress. One limitation of our study is that the compound or compounds that actually have this beneficial effect in the extracts remain unknown at this time. Therefore, the future studies should be focused on the identification of the components in the extracts that exhibit anti-oxidative and hypoglycemic effects.ConclusionTaken together, our studies using different experimental paradigms indicate that Ta-ermi extracts possess antioxidant and anti-diabetic properties and may be employed as functional food ingredients for the remission of diabetes.

Diabetes-induced upregulation of kallistatin levels exacerbates diabetic nephropathy via RAS activation.

Kallistatin is an inhibitor of tissue kallikrein and also inhibits the Wnt pathway. Its role in diabetic nephropathy (DN) is uncertain. Here we reported that serum kallistatin levels were significantly increased in diabetic patients with DN compared to those in diabetic patients without DN and healthy controls, and positively correlated with urinary albumin excretion. In addition, renal kallistatin levels were significantly upregulated in mouse models of type 1 (Akita, OVE26) and type 2 diabetes (db/db). To unveil the effects of kallistatin on DN and its underlying mechanism, we crossed transgenic mice overexpressing kallistatin with OVE26 mice (KS‐tg/OVE). Kallistatin overexpression exacerbated albuminuria, renal fibrosis, inflammation, and oxidative stress in diabetes. Kallikrein activity was inhibited while the renin‐angiotensin system (RAS) upregulated in the kidney of KS‐tg/OVE mice compared to WT/OVE mice, suggesting a disturbed balance between the RAS and kallikrein‐kinin systems. As shown by immunostaining of endothelial makers, renal vascular densities were decreased accompanied by increased HIF‐1α and erythropoietin levels in the kidneys of KS‐tg/OVE mice. Taken together, high levels of kallistatin exacerbate DN at least partly by inducing RAS overactivation and hypoxia. The present study demonstrated a positive correlation between kallistatin levels and DN, suggesting a potential biomarker for prognosis of DN.

Comparative pre- and post-treatment effects of Nigella sativa oil on lipid profile and antioxidant enzymes in a rat model of diabetes mellitus

Background: Lipid profile dysregulation and oxidative stress are important risk factors for cardiovascular disease in diabetic individuals. Nigella Sativa (NS) oil has been reported to have a favorable effect on triglycerides (TG) in rat models of diabetes mellitus. There is a dearth of information available about preventive or corrective use to manage and ameliorate diabetes. Aim: This study sought to ascertain the comparative pre and post-treatment effects of the oil on TG, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, and key antioxidant enzymes levels in diabetic rats. Methods: Thirty (30) Wistar rats were divided into 6 groups of 5 rats each as follows: Group I rats took normal chow ad libitum and served as Control. Group II rats were induced with diabetes using streptozocin (50 mg/Kg BW). Group III and IV rats were pre-administered with 0.5 and 1 ml of the oil, respectively, before induction, whereas Group V and VI rats were treated with 0.5 and 1 ml of the oil after induction. The listed parameters were assessed in the plasma at the end of the study. Results: Diabetes induction caused a significant increase in the TG level. There was no significant change in the oxidative stress parameters. Only post-administration caused a significant reduction in TG level, whereas both pre and post-administrations caused a significant improvement in HDL levels. Both pre- and post-administrations caused an increase in superoxide dismutase and catalase levels when causing a significant reduction in malondialdehyde level. Conclusion: Post-induction treatment may be more effective in the correction of lipid dysregulation and oxidative stress in diabetes.

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes.

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia as a consequence of pancreatic β cell loss and/or dysfunction, also caused by oxidative stress. The molecular mechanisms involved inβ cell dysfunction and in response to oxidative stress are also regulated by microRNAs (miRNAs). miRNAs are a class of negative gene regulators, which modulate pathologic mechanisms occurring in diabetes and its complications. Although several pharmacological therapies specifically targeting miRNAs have already been developed and brought to the clinic, most previous miRNA-based drug delivery methods were unable to target a specific miRNA in a single cell type or tissue, leading to important off-target effects. In order to overcome these issues, aptamers and nanoparticles have been described as non-cytotoxic vehicles for miRNA-based drug delivery. These approaches could represent an innovative way to specifically target and modulate miRNAs involved in oxidative stress in diabetes and its complications. Therefore, the aims of this review are: (i) to report the role of miRNAs involved in oxidative stress in diabetes as promising therapeutic targets; (ii) to shed light onto the new delivery strategies developed to modulate the expression of miRNAs in diseases.

3233 Massive Gastric Distention… Aaand It's Gone!

INTRODUCTION: Gastric outlet obstruction is usually a sequelae of malignancy or PUD. When these causes are ruled out, other etiologies like gastroparesis should be considered. CASE DESCRIPTION/METHODS: A 72 year old female nursing home resident with a history of schizophrenia, depression, dementia (on Mirtazapine, Trazodone, and Donepezil), hypothyroidism, and longstanding type 2 diabetes with a Hemoglobin A1c of 6.1% was admitted with abdominal pain, emesis, and increased agitation. CT of the abdomen and pelvis revealed marked fluid filled distention of the stomach and proximal duodenum with no clear gastric outlet obstruction (Figure 1). Nasogastric tube placement was not tolerated by the patient. She was then made NPO and gradually advanced to a clear liquid diet. EGD performed six days later revealed a normal duodenum with mild stomach distention and no evidence of gastric outlet obstruction (Figures 2 and 3). Her symptoms then resolved and she was discharged. DISCUSSION: Our patient presented with non-obstructive, massive gastric distention, which improved rapidly with dietary restriction. Gastroparesis was thought to be the primary diagnosis due to her risk factors of diabetes and psychotropic medication use. The cause of gastroparesis is most commonly idiopathic, but it is also linked to diabetes, certain medications, postsurgical injuries, hypothyroidism, and post viral syndromes. In diabetes oxidative stress and long-standing disease leading to autonomic dysfunction are postulated mechanisms for gastroparesis. A recent review demonstrated the following prevalence of gastroparesis over a 10 year time period: 5.2% in Type 1 Diabetes, 1.0% in Type 2 Diabetes, and 0.2% in controls. Additionally, antidepressants and antipsychotic medications (eg, anticholinergic, dopamine agonists, tricyclic antidepressants) have been suggested as possible triggers for gastroparesis. Commonly prescribed medications including calcium channel blockers, narcotics, glucagon-like peptide-1 agonists and amylin analogues have similar effects. Our case is interesting as it demonstrates how gastric distention can develop to a massive extent in the setting of offending drugs, despite well controlled diabetes. Patients with longstanding diabetes taking multiple psychiatric medications are at a particularly high risk of developing gastroparesis.

Aminoguanidine reduces diabetes-associated cardiac fibrosis.

Aminoguanidine (AG) inhibits advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP) accumulated as a result of excessive oxidative stress in diabetes. However, the molecular mechanism by which AG reduces AGE-associated damage in diabetes is not well understood. Thus, we investigated whether AG supplementation mitigates oxidative-associated cardiac fibrosis in rats with type 2 diabetes mellitus (T2DM). Forty-five male Wistar rats were divided into three groups: Control, T2DM and T2DM+AG. Rats were fed with a high-fat, high-carbohydrate diet (HFCD) for 2 weeks and rendered diabetic using low-dose streptozotocin (STZ) (20 mg/kg), and one group was treated with AG (20 mg/kg) up to 25 weeks. In vitro experiments were performed in primary rat myofibroblasts to confirm the antioxidant and antifibrotic effects of AG and to determine if blocking the receptor for AGEs (RAGE) prevents the fibrogenic response in myofibroblasts. Diabetic rats exhibited an increase in cardiac fibrosis resulting from HFCD and STZ injections. By contrast, AG treatment significantly reduced cardiac fibrosis, α-smooth muscle actin (αSMA) and oxidative-associated Nox4 and Nos2 mRNA expression. In vitro challenge of myofibroblasts with AG under T2DM conditions reduced intra- and extracellular collagen type I expression and Pdgfb, Tgfβ1 and Col1a1 mRNAs, albeit with similar expression of Tnfα and Il6 mRNAs. This was accompanied by reduced phosphorylation of ERK1/2 and SMAD2/3 but not of AKT1/2/3 and STAT pathways. RAGE blockade further attenuated collagen type I expression in AG-treated myofibroblasts. Thus, AG reduces oxidative stress-associated cardiac fibrosis by reducing pERK1/2, pSMAD2/3 and collagen type I expression via AGE/RAGE signaling in T2DM.

Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus.

Diabetes and Hypertension Differentially Affect Renal Catecholamines and Renal Reactive Oxygen Species.

Patients with diabetic hypertensive nephropathy have accelerated disease progression. Diabetes and hypertension have both been associated with changes in renal catecholamines and reactive oxygen species. With a specific focus on renal catecholamines and oxidative stress we examined a combined model of hypertension and diabetes using normotensive BPN/3J and hypertensive BPH/2J Schlager mice. Induction of diabetes (5 × 55 mg/kg streptozotocin i.p.) did not change the hypertensive status of BPH/2J mice (telemetric 24 h avg. MAP, non-diabetic 131 ± 2 vs. diabetic 129 ± 1 mmHg, n.s at 9 weeks of study). Diabetes-associated albuminuria was higher in BPH/2J vs. diabetic BPN/3J (1205 + 196/-169 versus 496 + 67/-59 μg/24 h, p = 0.008). HPLC measurement of renal cortical norepinephrine and dopamine showed significantly greater levels in hypertensive mice whilst diabetes was associated with significantly lower catecholamine levels. Diabetic BPH/2J also had greater renal catecholamine levels than diabetic BPN/3J (diabetic: norepinephrine BPN/3J 40 ± 4, BPH/2J 91 ± 5, p = 0.010; dopamine: BPN/3J 2 ± 1; BPH/2J 3 ± 1 ng/mg total protein, p < 0.001 after 10 weeks of study). Diabetic BPH/2J showed greater cortical tubular immunostaining for monoamine oxidase A and cortical mitochondrial hydrogen peroxide formation was greater in both diabetic and non-diabetic BPH/2J. While cytosolic catalase activity was greater in non-diabetic BPH/2J it was significantly lower in diabetic BPH/2J (cytosolic: BPH/2J 127 ± 12 vs. 63 ± 6 nmol/min/ml, p < 0.001). We conclude that greater levels of renal norepinephrine and dopamine associated with hypertension, together with diabetes-associated compromised anti-oxidant systems, contribute to increased renal oxidative stress in diabetes and hypertension. Elevations in renal cortical catecholamines and reactive oxygen species have important therapeutic implications for hypertensive diabetic patients.

Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function.

Luteolin has been reported to attenuate ischemia/reperfusion (I/R) injury in the diabetic heart through endothelial nitric oxide synthase- (eNOS-) related antioxidative response. Though the nuclear factor erythroid 2-related factor 2 (Nrf2) is regarded as a key endogenous factor to reduce diabetic oxidative stress, whether luteolin reduces cardiac I/R injury in the diabetic heart via enhancing Nrf2 function needs to be clarified. We hypothesized that pretreatment with luteolin could alleviate cardiac I/R injury in the diabetic heart by affecting the eNOS/Nrf2 signaling pathway. The diabetic rat was produced by a single injection of streptozotocin (65 mg/kg, i.p.) for 6 weeks, and then, luteolin (100 mg/kg/day, i.g.), eNOS inhibitor L-NAME, or Nrf2 inhibitor brusatol was administered for the succedent 2 weeks. After that, the isolated rat heart was exposed to 30 min of global ischemia and 120 min of reperfusion to establish I/R injury. Luteolin markedly ameliorated cardiac function and myocardial viability; upregulated expressions of heme oxygenase-1, superoxide dismutase, glutathione peroxidase, and catalase; and reduced myocardial lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R heart. All these ameliorating effects of luteolin were significantly reversed by L-NAME or brusatol. Luteolin also markedly reduced S-nitrosylation of Kelch-like ECH-associated protein 1 (Keap1) and upregulated Nrf2 and its transcriptional activity. This effect of luteolin on Keap1/Nrf2 signaling was attenuated by L-NAME. These data reveal that luteolin protects the diabetic heart against I/R injury by enhancing eNOS-mediated S-nitrosylation of Keap1, with subsequent upregulation of Nrf2 and the Nrf2-related antioxidative signaling pathway.

TCTAP A-055 Novel Rhynchophylline Analogue, Y396, Improves Endothelial Malfunction Induced by Oxidative Stress in Diabetes

Endothelial dysfunction appears in early diabetes mellitus. Whether Y396, a synthesized analogue of Uncaria rhynchophylla , could protect endothelial dysfunction and the underlying molecular mechanism is the problem we are trying to solve out. We established diabetes mellitus in mice by STZ

Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation.

Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation.

Chronic Inhibition of Mitochondrial Dihydrolipoamide Dehydrogenase (DLDH) as an Approach to Managing Diabetic Oxidative Stress.

Mitochondrial dihydrolipoamide dehydrogenase (DLDH) is a redox enzyme involved in decarboxylation of pyruvate to form acetyl-CoA during the cascade of glucose metabolism and mitochondrial adenine triphosphate (ATP) production. Depending on physiological or pathophysiological conditions, DLDH can either enhance or attenuate the production of reactive oxygen species (ROS) and reactive nitrogen species. Recent research in our laboratory has demonstrated that inhibition of DLDH induced antioxidative responses and could serve as a protective approach against oxidative stress in stroke injury. In this perspective article, we postulated that chronic inhibition of DLDH could also attenuate oxidative stress in type 2 diabetes. We discussed DLDH-involving mitochondrial metabolic pathways and metabolic intermediates that could accumulate upon DLDH inhibition and their corresponding roles in abrogating oxidative stress in diabetes. We also discussed a couple of DLDH inhibitors that could be tested in animal models of type 2 diabetes. It is our belief that DLDH inhibition could be a novel approach to fighting type 2 diabetes.

Commercially available non-nutritive sweeteners modulate the antioxidant status of type 2 diabetic rats.

Non-nutritive sweeteners (NNS) are increasingly being used by diabetics, but little is known about their effects on antioxidant status. We investigated the effects of ad libitum consumption of commercially available NNS (aspartame, saccharin, sucralose, and cyclamate-based sweeteners) on antioxidative markers in a rat model of type 2 diabetes (T2D). NNS consumption reduced (p<0.05) T2D-induced lipid peroxidation and boosted serum, hepatic, renal, cardiac, and pancreatic glutathione (GSH) levels. Catalase, glutathione reductase, superoxide dismutase, and glutathione peroxidase activity was increased in the serum and most organs upon diabetes induction, perhaps due to adaptative antioxidant response to the diabetes-induced lipid peroxidation. NNS showed varying effects on serum and tissue antioxidant enzymes of animals. An antioxidant capacity scores sheet of NNS, suggest that aspartame-based NNS may not exert antioxidant effects in diabetics, while saccharin-based NNS may be a potent antioxidative sweetener as seen in the animal model of T2D. PRACTICAL APPLICATIONS: The use of NNS is becoming more popular, especially for diabetic individuals. While there are several commercial NNS available in the market, little is known about how they affect the antioxidant status of consumers. We therefore investigated how some commercially available NNS affect the antioxidant status of diabetic rats. Observed data revealed varying effects of NNS on serum and different organs, which suggest that some NNS may be better than others for diabetic oxidative stress and thus may be recommended for consumers. However, this finding is subject to additional corroborative clinical studies.

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice.

BACKGROUND/OBJECTIVESHyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes.MATERIALS/METHODSDiabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ≥ 250 mg/dL), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks.RESULTSGT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear factor-κB pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice.CONCLUSIONThe findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Protective effect of Schisandra chinensis extracts against H2O2-induced oxidative damage in RINm5F cells

Objective: To study the protective effect of Schisandra chinensis extracts (SCEs) on the RINm5F cells against H2O2-induced oxidative damage and to provide a basis for the study of the role of SCEs in the prevention and treatment of diabetic oxidative stress. Materials and Methods: We performed ultrasonic preparation of SCEs and verified the presence of 8 lignans by high-performance liquid chromatography (HPLC). An in vitro model of H2O2-induced oxidative damage was established using RINm5F cells and treated with various concentrations of SCEs (high dose, medium dose, and low dose). The antioxidative activity of SCEs was observed and its mechanisms were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, and measuring malondialdehyde (MDA) and superoxide dismutase assay (SOD) according to the instructions of kits. Results: The total lignan content in SCEs was 18.86 mg/mL; the concentration of 8 kinds of lignans were schisandrin, 5.99 mg/mL; schisandrol B, 3.27 mg/mL; schisantherin A, 1.99 mg/mL; schisanhenol, 0.94 mg/mL; anwulignan, below the detection limit; deoxyschisandrin, 1.33 mg/mL; schisandrin B, 3.95 mg/mL; and schisandrin C, 1.39 mg/mL. SCEs promoted proliferation of islet cells and exhibited a protective effect against H2O2-induced oxidative damage in islet cells. The cell survival rates in the high-dose and medium-dose SCEs groups were greater than that in the model group by 63.4% and 45.6%, respectively; the protective effect of SCEs against oxidative damage was dose dependent. The intracellular MDA content was significantly decreased (P Abbreviation used: Schisandra chinensis Extracts (SCEs).