Diabetes-induced Oxidative Stress Research Articles

Protective Effect of Aloe vera (L.) on Diabetes-Induced Oxidative Stress Linked Spermiological Co-Morbidity in Human and Rat: An In-Vitro Analysis.

Diabetes linked reproductive complications are rising problems nowadays. The study focused on the protective efficacy of Aloe vera (L.) on sperm cell damage in an oxidative stress milieu encumbered by a chronic diabetes in human and streptozotocin treated Wistar rat (Rattus norvegicus). Spermatozoa from rat's epididymal washing, and human semen after 3-4days of abstinence of mating or masturbation were collected from control and diabetes groups. Spermatozoa of human and rat were incubated for 1 or 2h at 370C in an in-vitro medium separately and considered as normo-glycemic control and diabetes sub-groups. Dose of 1 or, 2 or, 4mg/ml of Aloe vera (L.) hydro-ethanolic (40:60) extract (AVHE) was given to diabetes samples, considered as sub-sub-group for assessing its protective effect on spermiological and oxidative stress parameters. The motility, viability, plasma membrane integrity, nuclear chromatin decondensation for DNA fragmentation, acrosome cap status, and antioxidative status of human and rat spermatozoa were decreased whereas spermatozoal apoptosis was elevated significantly (p < 0.05), noted by TUNEL assay in diabetes samples compared to the duration-matched control group. Exposure of AVHE to diabetes samples resulted significant rectification (p < 0.05) in the said parameters than the unexposed diabetes group. In control group, AVHE exposure has significant protective effect from spermiological deterioration compared to unexposed control group. Identification of major phytomolecules in AVHE was done by LC-MS study. Diabetes-induced oxidative stress-mediated spermatozoal injuries can be protected by AVHE extract, raise the possibility for potentiating sperm of human for increasing the success rate of in-vitro fertilization-blastocyst implantation.

Potential of Sorghum Seeds in Alleviating Hyperglycemia, Oxidative Stress, and Glycation Damage.

Diabetes mellitus, characterized by dysregulated glucose metabolism, oxidative stress, and the formation of advanced glycation end products, poses a significant global health burden. In this study, we explored the potential of sorghum (Sorghum bicolor) seeds, known for their abundant phytochemical composition, as a natural remedy for diabetes and its associated damage. High-performance liquid chromatography/high-resolution mass spectrometry analysis revealed a remarkable phenolic richness in sorghum grains, including gallic acid, quercetin, and the predominant procyanidin B-1, with ecotype-specific variations in flavonoid distribution. Elemental analysis by ICP showed an abundance of macro-elements (Ca, K, Mg), trace elements (Fe, Mn, Si, Zn), and ultra-trace elements (B, Co, Cr, Cu, Mo, Se, V) essential for human health, supporting its therapeutic and nutritional potential. Additionally, the results demonstrated variable total phenolic contents (188-297 mg GAE/g dE) and total flavonoid contents (66-78 mg QE/g dE), with corresponding differences in antioxidant activities across the five ecotypes. Treatment with sorghum seed extract (SE1) significantly reduced oxidative stress markers, such as malondialdehyde (MDA)by 40% and hydrogen peroxide (H2O2) by 63%, in diabetic mice, compared to untreated diabetic controls. Moreover, sorghum extracts exhibited a remarkable increase in antioxidant enzyme activities, including a 50% increase in superoxide dismutase (SOD) activity and a 60% increase in glutathione peroxidase (GPx) activity, indicating their potential to bolster antioxidant defenses against diabetes-induced oxidative stress. These findings underscore the therapeutic potential of sorghum seeds in diabetes management and prevention, paving the way for the development of functional foods with enhanced health benefits.

Atorvastatin ameliorates diabetic nephropathy through inhibiting oxidative stress and ferroptosis signaling.

Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The present study investigated the effects of atorvastatin on diabetes renal injury and ferroptosis signaling. A mouse model of diabetes was established by the intraperitoneal injection of streptozotocin (50 mg/kg/day) plus a high fat diet with or without atorvastatin treatment. Diabetes mice manifested increased plasma glucose and lipid profile, proteinuria, renal injury and fibrosis, atorvastatin significantly lowered plasma lipid profile, proteinuria, renal injury in diabetes mice. Atorvastatin reduced renal reactive oxygen species (ROS), iron accumulation and renal expression of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), transferrin receptor 1 (TFR1), and increased renal expression of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2) and ferritin heavy chain (FTH) in diabetes mice. Consistent with the findings in vivo, atorvastatin prevented high glucose-induced ROS formation and Fe2+ accumulation, an increase in the expression of 4-HNE, MDA and TFR1, and a decrease in cell viability and the expression of NRF2, GPX4 and FTH in HK2 cells. Atorvastatin also reversed ferroptosis inducer erastin-induced ROS production, intracellular Fe2+ accumulation and the changes in the expression of above-mentioned ferroptosis signaling molecules in HK2 cells. In addition, atorvastatin alleviated high glucose- or erastin-induced mitochondria injury. Ferroptosis inhibitor ferrostatin-1 and antioxidant N-acetylcysteine (NAC) equally reversed the expression of high glucose-induced ferroptosis signaling molecules. Our data support the notion that statins can inhibit diabetes-induced renal oxidative stress and ferroptosis, which may contribute to statins protection of diabetic nephropathy.

Angiotensin II Type 1 receptor blockade attenuates the neuropathological changes in the spinal cords of diabetic rats with modulation of nuclear factor erythroid 2-related factor 2/ heme oxygenase 1 system

Peripheral and central neuropathies frequently complicate worldwide diabetes. Compared to peripheral neuropathy, central neuropathy didn`t gain a major research interest. Angiotensin II is reported to be involved in diabetic neuropathic pain but its role in the central pathological changes in the spinal cord is not clear. Here, we study the role of Losartan; an Angiotensin II receptor 1 (AT1) antagonist in suppression of the diabetes-induced changes in the spinal cord. Three groups of rats were applied; a negative control group, a streptozotocin (STZ) diabetic group, and a group receiving STZ and Losartan. After two months, the pathological alteration in the spinal cord was investigated, and an immunohistochemical study was performed for neuronal, astrocytic, and microglial markers; nuclear protein (NeuN), Glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adaptor molecule 1 (Iba1), respectively, and for an apoptosis marker; caspase-3, and the inflammatory marker; nuclear factor kappa B (NF-kB) signaling, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); physiological antioxidant system. The results showed that Losartan caused recovery of spinal cord changes, by inhibiting the microglial and astrocytic activation, suppressing neuronal apoptosis and NF-kB expression with activation of Nrf2/HO-1 (P<0.0005). It is suggested, herein, that Losartan can suppress diabetes-induced glial activation, inflammation, neuronal apoptosis, and oxidative stress in the spinal cord; the mechanisms that may underlie the role of AT1 antagonism in suppressing diabetic neuropathic pain.

Therapeutic potentials of Hibiscus trionum: Antioxidant, anti-lipid peroxidative, hypoglycemic, and hepatoprotective effects in type 1 diabetic rats

Recent advances in diabetes treatment have primarily focused on insulin and hypoglycemic agents; however, there is growing interest in exploring herbal and synthetic alternatives. Numerous studies have highlighted the preventive effectiveness of regular plant consumption in managing chronic conditions, particularly diabetes. Hibiscus, a medicinal plant recognized in various cultures, is known for its diverse health benefits. This study investigated the impact of Hibiscus trionum on glycemic control and assessed its influence on glucose and insulin levels in diabetes-induced rats. The concentrations of antioxidant enzymes, particularly superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were scrutinized across multiple body tissues (plasma, heart, muscle, liver, and kidney). The malondialdehyde (MDA) concentration, an indicator of lipid peroxidation, was examined in both plasma and tissue samples. Serum total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were evaluated. Diabetic Group (D) exhibited a significant decrease in body weight, increased fluid and food consumption, elevated blood glucose levels, and increased antioxidant enzyme activity. Moreover, the diabetic group also showed increased levels of MDA, TC, TG, AST, and ALT, along with reduced insulin levels, compared to the control group. A substantial improvement in all parameters impaired by diabetes was observed following the application of Hibiscus trionum (HTT) in the Diabetes+HTT group. The antioxidative stress-reducing, lipid peroxidation-improving, and hepatoprotective potential of Hibiscus trionum in mitigating diabetes-induced oxidative stress is noteworthy. These findings indicate that HTT supplementation has valuable beneficial effects in protecting against the harmful impacts of diabetes.

The nutritional value and health properties of tahini and tahini-based products

Tahini is an oily paste made from mechanically hulled, roasted and ground sesame, which is used as an ingredient in many traditional Middle Eastern recipes. It is rich in MUFAs, PUFAs, polyphenols, minerals and vitamins. Literature about the health effects of tahini consumption is limited since only two studies in human population and one study in animal model are available, so far. A 6-week supplementation with 28 g tahini in T2DM patients led to lower TG and hs-CRP and higher HDL-C levels. Additionally, consumption of 50 g tahini decreased plasma glucose and increased total phenolic content, urinary 8-iso-prostaglandin F2a and flow-mediated dilatation in healthy individuals postprandially. Moreover, in 40 male albino rats of Wistar strain, sesame butter decreased glucose and malondialdehyde and increased HDL-C and total antioxidant capacity compared to control. Hummus is a dip or spread made from boiled chickpeas, blended with tahini, lemon juice, olive oil, garlic and salt. It is rich in vitamins, minerals and different bioactive compounds including phytic acid, tannins, carotenoids, sterols, and other polyphenols. Hummus consumption has been positively related with weight management and glucose-insulin response. Halva is a low-moisture confectionery that contains tahini, sugar, citric acid and Saponaria officinalis root extract and its consumption has been found to ameliorate glycemic control. In conclusion, tahini could be beneficial regarding diabetes-induced inflammation, oxidative stress and endothelial function. Since more research is needed in order to confirm the aforementioned properties, tahini and tahini-based products seem to be a healthy choice, aiming at promoting healthy dietary patterns.

Resolvins protect against diabetes-induced colonic oxidative stress, barrier dysfunction, and associated diarrhea via the HO-1 pathway.

Diabetes is associated with increased oxidative stress, leading to altered tight junction formation and increased apoptosis in colonic epithelial cells. These changes may lead to intestinal barrier dysfunction and corresponding gastrointestinal symptoms in patients with diabetes, including diarrhea. The aim of this study was to characterize the effect and mechanism of Resolvin D1 (RvD1) on diabetes-induced oxidative stress and barrier disruption in the colon. Mice with streptozotocin-induced diabetes were treated with RvD1 for 2 weeks, then evaluated for stool frequency, stool water content, gut permeability, and colonic transepithelial electrical resistance as well as production of reactive oxygen species (ROS), apoptosis, and expression of tight junction proteins Zonula Occludens 1 (ZO-1) and occludin. The same parameters were assessed in human colonoid cultures subjected to elevated glucose. We found that RvD1 treatment did not affect blood glucose, but normalized stool water content and prevented intestinal barrier dysfunction, epithelial oxidative stress, and apoptosis. RvD1 also restored ZO-1 and occludin expression in diabetic mice. RvD1 treatment increased phosphorylation of Akt and was accompanied by a 3.5-fold increase in heme oxygenase-1 (HO-1) expression in the epithelial cells. The protective effects of RvD1 were blocked by ZnPP, a competitive inhibitor of HO-1. Similar findings were observed in RvD1-treated human colonoid cultures subjected to elevated glucose. In conclusion, Oxidative stress in diabetes results in mucosal barrier dysfunction, contributing to the development of diabetic diarrhea. Resolvins prevent ROS-mediated mucosal injury and protect gut barrier function by intracellular PI3K/Akt activation and subsequent HO-1 upregulation in intestinal epithelial cells. These actions result in normalizing stool frequency and stool water content in diabetic mice, suggesting that resolvins may be useful in the treatment of diabetic diarrhea.

Biochemical Evaluation of Adansonia Digitata Methanolic Leaf and Stem Bark Extract on Streptozotocin Induced Diabetic Rats

Several herbal preparations are used to treat diabetes; however, their overall biochemical effects other than hypoglycemic effects are scanty. This study therefore was designed to evaluate the effect of methanolic extract of leaves and stem-bark of Adansonia digitata on biochemical indices of streptozotocin-induced diabetic rats. Sixty-three wistar rats were distributed into 9 groups of 7 each. The test animals were intraperitoneally administered with single dose of 50 mg/kg streptozotocin and monitored for 72 hours for development of hyperglycemia. Diabetic rats were treated in 12 h cycles for three weeks with 100 mg/kg, 200 mg/kg and 300 mg/kg of both leaves and stem-bark of Adansonia digitata methanolic extract and metformin (50 mg/kg). Non-diabetic control rats received a lacebo of distilled water. Group 1 served as normal control, group 2 served as diabetic control, while groups 4-9 were diabetic rats treated orally with methanolic leave and stem-bark extracts of Adansonia digitata (100 mg/kg, 200 mg/kg and 300 mg/kg) for 21days. Group 3 animals were diabetic rats treated with anti-diabetic drug (metformin 50 mg/kg). The levels of fasting blood sugar (FBS), electrolytes (Na+, K+, Cl-), Urea and creatinine Triglyceride (TG), Cholesterol (CHOL), thiobarbituric acid reactive substance (TBARS), White Blood Cell (WBC) count, Red Blood Cell (RBC) count, Haemoglobin (HGB), Hematocrit (HCT), Platelet (PLT), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH), Mean Cell Haemoglobin Concentration (MCHC), Lymphocyte (LYM), aspartatate aminotransfrease (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), catalase (CAT) and superoxide dismutase (SOD) activities total, total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentrations were assayed. The results indicated that the concentrations of Na+, K+, Cl-, creatinine, urea TBARS, ALT, AST, ALB, CHOL and IB bilirubin were significantly (p&lt;0.05) increased, while the levels of WBC, RBC, HGB, HCT, PLT, LYM, MCV SOD and CAT were reduced in the diabetic control (p&lt;0.05). The Adansonia digitata methanolic leaves and stem-bark extract significantly increased WBC, RBC, HGB, HCT, PLT, MCV, LYM, TP, CAT and SOD activity and reduced the FBS, Na+, K+, Cl-, TBARS, ALT, AST, creatinine, urea and bilirubin concentrations significantly (p&lt;0.05) compared to normal control. However, treatment with metformin showed slight modification in the changes observed compared to Adansonia digitata methanolic leaves and stem-bark extract. MCV and MCHC reduced non-significantly (p&gt;0.05) in the diabetic animals as compared to the normal control and the extract-treated rats, while they increased non- significantly (p&gt;0.05) in the test groups when compared to the diabetic control. Levels of TB, DB, and TG showed non-significant (p&lt;0.05) increase in diabetic control, but treatment with extracts and metformin caused non-significant decrease (p&lt;0.05). Diabetic control exhibited significantly (p&lt;0.05) decreased ALB levels and non-significant TP decrease compared to normal control, while Adansonia digitata extracts and metformin significantly increased ALB and non-significantly increased TP levels compared to diabetic control. The study concluded that Adansonia digitata extracts reversed diabetes-induced oxidative stress in rat hepatocytes, potentially through beta cell regeneration or insulin release stimulation, suggesting their potential for managing diabetic complications.

Synergistic antioxidant and anti-inflammatory effects of combined supplementation with oral zinc and dietary Moringa oleifera leaf in streptozotocin-induced diabetic rats

Individual interventions with zinc or M. oleifera leaf powder have shown some promise in managing diabetes-induced oxidative stress and inflammation. This study examined the synergistic effect of oral zinc and dietary M. oleifera leaf supplementation on the serum antioxidant and anti-inflammatory activities in streptozotocin-induced diabetic rats. Seven groups of 56 rats were used in the experiment: (1) normal rats + normal diet, (2) normal rats + 3% M. oleifera leaf-supplemented diet, (3) non-treated diabetic rats, (4) diabetic rats + 200 mg/kg metformin, (5) diabetic rats + 3% M. oleifera leaf-supplemented diet, (6) diabetic rats + 100 mg/kg oral zinc sulfate, and (7) diabetic rats + 3% M. oleifera leaf-supplemented diet + 100 mg/kg oral zinc sulfate. ELISA assay kits were used for antioxidant and anti-inflammatory markers respectively. The results suggest that when all treated diabetic groups were compared with non-treated diabetic control at p&lt;0.05, only groups 4 and 7 showed a significant increase in superoxide dismutase activity. Only group 5 showed a significant increase in reduced glutathione. No significant changes were observed in catalase and the total antioxidant capacity. MDA decreased significantly in group 7 only. There was a significant reduction in interleukin-6 in groups 6 and 7. Only group 7 showed significantly reduced C-reactive protein. Tumor necrosis factor-α reduced significantly in group 6 only. Overall, the combined supplementation with zinc and M. oleifera outperformed the individual treatments with either zinc or M. oleifera in ameliorating diabetes-induced oxidative stress and inflammation, indicating a possible synergistic effect of their combination.

Protective role of eugenol against diabetes-induced oxidative stress, DNA damage, and apoptosis in rat testes.

Diabetes mellitus, a metabolic disorder alters gonadal development and spermatogenesis,reactive oxygenspecies production, DNA damage, and apoptosis, which subsequently lead to male subfertility. Eugenol is an antioxidant, traditionally used as medication for digestive disorders and antioxidant therapy, decrease transport of glucose from GIT to systemic circulation. This experiment was aimed to decipher cellular and molecular insights of eugenol in protecting diabetic germ cells in rats. Rats were assigned randomly into five groups: control, eugenol control (Eugenol 400; EUG), diabetic (DIA), diabetic + eugenol 100 (DIA + EUG 100), and diabetic + eugenol 400 (DIA + EUG 400). EUG 400 and DIA + EUG 400 groups received 400 mg/kg eugenol orally. DIA + EUG 100 group received 100 mg/kg eugenol. Treatment was conducted for 4 weeks. Type 1 diabetes was induced by injecting a single i.p. dose of streptozotocin (55 mg/kg). Morphometric, biochemical, sperm parameters, oxidative stress, hormonal levels, histopathology, and fibrosis in the testis and epididymis, were evaluated. DNA damage was evaluated using halo and comet assays; DNA fragmentation and apoptosis using TUNEL assay. Eugenol treatment significantly normalized biochemical parameters, reduced MDA while increased albumin and GSH levels in diabetes. Eugenol significantly increased sperm numbers, motility and attenuated abnormal sperm head morphology in diabetes. Moreover, eugenol significantly reversed diabetes-induced cellular damages, altered spermatogenesis, and collagen deposition in testis and epididymis. It also significantly attenuated diabetes-associated DNA breaks and apoptosis. These findings suggest that 4 weeks treatment with 400 mg/kg of eugenol could be beneficial for diabetic patients to prevent subfertility.

Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic hACE2 Mice through RAAS and TLR Signaling Activation.

Diabetics are more vulnerable to SARS-CoV-2 neurological manifestations. The molecular mechanisms of SARS-CoV-2-induced cerebrovascular dysfunction in diabetes are unclear. We hypothesize that SARS-CoV-2 exacerbates diabetes-induced cerebrovascular oxidative stress and inflammation via activation of the destructive arm of the renin-angiotensin-aldosterone system (RAAS) and Toll-like receptor (TLR) signaling. SARS-CoV-2 spike protein was injected in humanized ACE2 transgenic knock-in mice. Cognitive functions, cerebral blood flow, cerebrovascular architecture, RAAS, and TLR signaling were used to determine the effect of SARS-CoV-2 spike protein in diabetes. Studies were mirrored in vitro using human brain microvascular endothelial cells treated with high glucose-conditioned media to mimic diabetic conditions. Spike protein exacerbated diabetes-induced cerebrovascular oxidative stress, inflammation, and endothelial cell death resulting in an increase in vascular rarefaction and diminished cerebral blood flow. SARS-CoV-2 spike protein worsened cognitive dysfunction in diabetes compared to control mice. Spike protein enhanced the destructive RAAS arm at the expense of the RAAS protective arm. In parallel, spike protein significantly exacerbated TLR signaling in diabetes, aggravating inflammation and cellular apoptosis vicious circle. Our study illustrated that SAR-CoV-2 spike protein intensified RAAS and TLR signaling in diabetes, increasing cerebrovascular damage and cognitive dysfunction.

Modulatory effects of extract of Heinsia crinita against fructose/streptozotocin-induced oxidative stress in diabetic rat models

Oxidative stress plays a crucial role in the development of type 2 diabetes and the associated microvascular and cardiovascular complications. In the study, we have investigated the effects of Heinsia crinita (H. crinita) extracts on lipid peroxidation and oxidative stress responses using diabetic rats. Type 2 diabetes was induced with 10 % fructose/40 mg/kg body weight streptozotocin (STZ). H. crinita extract was administered at 200 and 400 mg/kg body weight twice daily for 21 days, in addition to metformin (MET: 500 mg/kg body weight) control. Molecular docking analysis was performed to determine the binding affinity of H. crinita extracts to the DNA binding domains of peroxisome proliferator-activated receptor (Ppar) and retinoid x receptor (Rxr) protein crystal structures, showing different binding affinities for putative active compounds from the plant. Fasting blood glucose (FBG), body and organ weight changes were determined showing that H. crinita extract induced an anti-hyperglycemic effect in the treated animals, with changes (either decrease or increase) in liver and kidney weights. A decrease in mRNA expression of peroxisome proliferator-activated receptors (ppar), sterol regulatory element-binding protein 1 (srebp-1c), liver x-receptor (lxr), retinoid x receptors (rxr), cytochrome p45041 (cyp4a1) and acyl-CoA oxidase (acox1) in diabetic animals were observed, compared to the control. A dose-specific decrease or increase in antioxidant enzymes (superoxide dismutase: SOD, catalase: CAT, reduced glutathione: GSH, glutathione peroxidase: GPx) transcripts and activity levels were also observed. We also observed exposure-specific decrease or increase of malondialdehyde (MDA) levels. Our data suggested that H. crinita extract possesses protective effects against diabetes-induced oxidative stress. These effects might be attributed to their binding and activation of nuclear receptors, indicating their cellular mode of action that is comparable to MET.

MG132, Attenuates the Retinal Vascular Injury Through the Upregulation of Nrf2 Expression.

Purpose: This study clarifies the beneficial effects of MG132, a proteasomal inhibitor, on retinal vascular injury mediated by diabetes-induced oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: Diabetic rats and control animals were randomly assigned to receive MG132 or vehicle for 24 weeks, and human retinal endothelial cells (HRECs) were incubated with normal or high glucose with or without MG132. 26S proteasome activity in the rat retinas or cultured HRECs was measured using Suc-LLVY-7-amido-4-methylcoumarin. NADPH-quinone oxidoreduc-tase (NQO1), heme oxygenase (HO)-1, kelch-like ECH-associated protein 1 (Keap1) and Nrf2 were examined by Western blotting and real-time reverse transcription polymerase chain reaction. Cell apoptosis is measured through flow cytometry assay, mitochondrial reactive oxygen species (ROS) production, and retinal vascular leakage were assayed using CM-H2DCFDA fluorescent probes and Evans blue, respectively. Results: MG132 significantly inhibited the activation of 26S proteasome induced by diabetes or elevated glucose, and subsequently increased the expression of Nrf2, NQO1, and HO-1, and further reduced ROS accumulation. These changes were associated with a decrease of diabetes-induced retinal vascular leakage and retinal capillary cell apoptosis. Conclusions: MG132 decreases diabetes-induced 26S proteasome activation and exerts protective effects against retinal microvascular dysfunction in diabetic rats in association with the alleviation of retinal oxidative stress mediated by Nrf2.

Nutritional Content and Benefits of Coconut Water for the Diabetes Metabolism: a Narrative Review

Background: Coconut water is one of the natural food products that is widely available around the world. This commodity provides nutritional content that could increase rehydration status and improve health. The application of coconut water to health, including improving type 2 diabetes metabolism, has gotten research interest in recent years. Objectives: This narrative review paper aimed to summarize several articles about the nutritional content and the mechanism of the potential bioactive component in coconut water to improve type 2 diabetes metabolism. Methods: This study design was a narrative review of several articles from five databases search: PubMed/MEDLINE, Scielo, PsycINFO, Microsoft Academic, and Google Scholar. Discussion: Coconut water includes several biologically active components such as protein, amino acid, fatty acid, mineral, vitamin, and phenolic compounds. The recent discovery of nutrient content, especially antioxidant properties, and arginine in coconut water, signifies a good potential in improving type 2 diabetes mellitus. Antioxidant and arginine altered blood glucose, glycated hemoglobin, serum creatinine, blood urea, albumin, albumin/globulin ratio, liver function enzyme, lipid profile, antioxidant status, and lipid peroxidation without any significant hepatocellular damage. Arginine enhanced the nitric oxide synthase activity in the liver and arginine levels in the plasma. In mammals, the arginine-nitric oxide system, which includes AMPK, cGMP, PGC-1α, and PI3K, can maintain blood glucose homeostasis, increase insulin sensitivity, and prevent diabetes-induced oxidative stress. Conclusion: Coconut water can help to improve metabolism in type 2 diabetes mellitus conditions through antioxidant activity and arginine content.

Anti-oxidant effect of nitrite in the pancreatic islets of type 2 diabetic male rats.

Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type 2 diabetes (T2D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets. T2D was created in male rats using a combination of streptozotocin at 25 mg/kg and a high-fat diet. Wistar rats were assigned to 3 groups (n=6 in each group), including control, T2D, and T2D+nitrite; the latter group consumed drinking water containing sodium nitrite (50 mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox1, 2, 3, and 4), superoxide dismutase (SOD1, 2, and 3), glutathione peroxides (GPX1 and 7), glutathione reductase (GR), catalase, thioredoxin (TXN1 and 2), and thioredoxin reductase (TXNRD1) were measured in the isolated pancreatic islets. In the islets of diabetic rats, mRNA expressions of Nox1, 2, and 4 were higher, whereas expressions of SOD1, 2, catalase, GPX1, 7, GR, and TXN1 were lower than controls. Nitrite significantly (all P-values<0.05) decreased gene expression of Nox1 (0.39-fold) and Nox4 (0.23-fold) and increased gene expression of SOD1 (2.2-fold), SOD2 (2.8-fold), catalase (2.7-fold), GPX1 (2.2-fold), GPX7 (6.0-fold), GR (3.0-fold), TXN1 (2.1-fold), and TXNRD1 (2.3-fold) in diabetic rats. Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T2D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitrite-induced insulin secretion is partially due to decreased oxidative stress.

Beneficial role of broccoli and its active ingredient, sulforaphane in the treatment of diabetes

BackgroundBroccoli and its active ingredient, sulforaphane were reported to possess tremendous pharmacological activities such as anticancer, antimicrobial, antidepressant, antihypertensive and antidiabetic to mention but few. Here in, the antidiabetic potential of broccoli and sulforaphane (clinical trials, in vivo and in vitro models) were critically reviewed and discussed. MethodsRelevant articles were sourced from the major scientific databases (Scopus, PubMed, and Google Scholar). ResultsCollectively, the data revealed that broccoli and sulforaphane have the potential to reduce hyperglycemia, hyperlipidemia, insulin resistance and diabetes-induced oxidative stress. Such activities were linked to but not limited to the activation of Nrf2 and PI3K/Akt pathways, inhibitions of NF-κB, GSK3β, α-glucosidase and DPP-IV activities. ConclusionWith the current available clinical evidence, broccoli and sulforaphane are regarded as adjuncts in diabetes treatment but not classical antidiabetic drugs. Further detail clinical trials are warranted especially the phases II and III, where large number of diabetic patients will be recruited. In addition, improving bioavailability while improving efficacy and reducing toxicity are of paramount.

Abstract 110: Why Diabetics Are More Vulnerable To Cerebrovascular Complications Of SARS-CoV-2? An In-vivo Animal Study

Diabetics are more vulnerable to SARS-CoV-2 cerebrovascular complications, including brain fog, cognitive impairment, and strokes. This study aims to identify the molecular mechanisms of SARS-CoV-2-induced cerebrovascular dysfunction in diabetes. We hypothesize that SARS-CoV-2 exacerbates diabetes-induced cerebral oxidative stress and inflammation via activation of the destructive arm of the renin-angiotensin system (RAAS) and Toll-Like receptor (TLR) signaling. Methods: SARS-CoV-2 spike-protein binds to human angiotensin-converting enzyme-2 (ACE2) receptors but not murine Ace2. Therefore, type-2 diabetes was induced in humanized ACE2 (hACE2) knock-in transgenic mice using low-dose streptozotocin followed by eight weeks of a high-fat diet. Recombinant SARS-CoV-2 spike-protein was injected intravenously in control and diabetic mice. Cognitive functions were tested using Y-maze and Barnes maze. RAAS system and TLR signaling were assessed using RT-PCR and western blot analysis. The cerebrovascular architecture was measured using immunohistochemistry. Results: Diabetes increased cerebrovascular oxidative stress markers NOX1 and NOX5 and inflammatory markers Il-6, Il-1β, and TNF-α gene expression (P&lt;0.05). Diabetes upregulated angiotensin II and angiotensin 1 receptor (AT1R) expression, these effects were amplified by spike-protein (P&lt;0.05). Moreover, spike-protein injection decreased RAAS protective arm, ACE2, and AT2R expression (P&lt;0.05). In parallel, spike-protein exacerbated TLR signaling in diabetes. Spike-protein increased the TLR-8 receptors and its ligands HMGB1 and S100 and downstream adaptor proteins MyD88, TRAF6, and NF-κB expression (P&lt;0.05). Spike-protein significantly increased cerebrovascular rarefaction and cognitive dysfunction in diabetes (P&lt;0.05). Conclusion: SAR-CoV-2 spike-protein intensified RAAS and TLR signaling in diabetes leading to additional cerebrovascular damage and cognitive dysfunction. Targeting RAAS and TLR singling are possible therapeutic strategies to protect against SAR-CoV-2-induced cerebrovascular dysfunction in diabetes.

Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells.

Diabetes-induced oxidative stress induces the development of vascular complications, which are significant causes of morbidity and mortality in diabetic patients. Among these, diabetic retinopathy (DR) is often caused by functional changes in the blood-retinal barrier (BRB) due to harmful oxidative stress events in lipids, proteins, and DNA. Docosahexaenoic acid (DHA) has a potential therapeutic effect against hyperglycemia-induced oxidative damage and apoptotic pathways in the main constituents of BRB, retinal pigment epithelium cells (ARPE-19). Effective antioxidant response elicited by DHA is driven by the activation of the Nrf2/Nqo1 signaling cascade, which leads to the formation of NADH, a reductive agent found in the cytoplasm. Nrf2 also induces the expression of genes encoding enzymes involved in lipid metabolism. This study, therefore, aims at investigating the modulation of lipid metabolism induced by high-glucose (HG) on ARPE-19 cells through the integration of metabolic imaging and molecular biology to provide a comprehensive functional and molecular characterization of the mechanisms activated in the disease, as well the therapeutic role of DHA. This study shows that HG augments RPE metabolic processes by enhancing lipid metabolism, from fatty acid uptake and turnover to lipid biosynthesis and β-oxidation. DHA exerts its beneficial effect by ameliorating lipid metabolism and reducing the increased ROS production under HG conditions. This investigation may provide novel insight for formulating novel treatments for DR by targeting lipid metabolism pathways.

Long-term resveratrol administration improves diabetes-induced pancreatic oxidative stress, inflammatory status, and β cell function in male rats

Diabetes is a metabolic disorder caused by insulin resistance or a defect in the pancreatic beta cells in insulin secretion. The aim of this study was to evaluate the possible effectiveness of long-term administration of resveratrol on inflammatory and oxidative stress markers in the pancreatic tissue of diabetic rats. Male Wistar rats (n = 24) were randomly divided into four groups of six animals, namely a healthy group, a healthy group receiving resveratrol, a diabetic control group, and a diabetic group receiving resveratrol. Diabetes was induced by single dose injection of streptozotocin (50 mg/kg; ip), 15 min after injection of nicotinamide (110 mg/kg; ip). Resveratrol was also administered by gavage (5 mg/kg/day) for 4 months. Administration of resveratrol alleviated hyperglycemia, weight loss and pancreatic β cell function measured by HOMA-β. Resveratrol improved oxidative stress (nitrate/nitrite, 8-isoprostane and glutathione) and proinflammatory markers (tumor necrosis factor α, cyclooxygenase 2, interleukin 6 and nuclear factor kappa B) in the pancreatic tissue of diabetic rats. Resveratrol administration had no significant effect on the activity of superoxide dismutase and catalase enzyme. These observations indicate that resveratrol administration may be effective as a beneficial factor in improving pancreatic function and reducing the complications of diabetes.