Streptozotocin-induced Diabetic Model Research Articles

Apolipoprotein M/sphingosine 1-phosphate protects against diabetic nephropathy

Diabetic nephropathy remains a common cause of end-stage renal failure and its associated mortality around the world. Sphingosine 1-phosphate (S1P) is a multifunctional lipid mediator and binds to HDL via apolipoprotein M (ApoM). Since HDL has been reported to be epidemiologically associated with kidney disease, we attempted to investigate the involvement of the ApoM/S1P axis in the pathogenesis/progression of diabetic nephropathy. In type 2 diabetic patients, the serum ApoM levels were inversely correlated with the clinical stage of diabetic nephropathy. The decline in the eGFR over a 5-year observation period proceeded more rapidly in subjects with lower serum ApoM levels. In a mouse model of streptozotocin-induced diabetes, deletion of ApoM deteriorated the phenotypes of diabetic nephropathy: the urinary albumin and plasma creatinine levels increased, the kidneys enlarged, and renal fibrosis and thickening of the basement membrane progressed. On the other hand, overexpression of ApoM ameliorated these phenotypes. These protective effects of ApoM were partially inhibited by treatment with VPC23019, an antagonist of S1P1 and S1P3, but not by treatment with JTE013, an antagonist of S1P2. ApoM/S1P axis attenuated activation of the Smad3 pathway, while augmented eNOS phosphorylation through the S1P1 pathway. Moreover, ApoM/S1P increased the SIRT1 protein levels and enhanced mitochondrial functions by increasing the S1P content of the cell membrane, which might cause selective activation of S1P1. ApoM might be a useful biomarker for predicting the progression of diabetic nephropathy, and the ApoM/S1P-S1P1 axis might serve as a novel therapeutic target for preventing the development/progression of diabetic nephropathy.

Efficacy of Polydeoxyribonucleotide in Promoting the Healing of Diabetic Wounds in a Murine Model of Streptozotocin-Induced Diabetes: A Pilot Experiment.

We assessed the efficacy of polydeoxyribonucleotide (PDRN) in accelerating the healing of diabetic wounds in a murine model of streptozotocin (STZ)-induced diabetes. After the creation of diabetic wounds, the mice of the PDRN SC, PDRN IP and PBS groups received a subcutaneous, an intra-peritoneal injection of PDRN and a subcutaneous injection of PBS, respectively. After euthanasia, time-dependent changes in the wound diameter and histologic scores were measured and vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and collagen types I and III were assessed for their expression levels. The PDRN SC and the PDRN IP groups showed a significantly smaller diameter of diabetic wounds, significantly higher histologic scores, a significantly greater expression of VEGF, a significantly lower expression of TGF-β1 and a significantly greater expression of collagen types I and III as compared with the PBS group (p < 0.05 or 0.0001). In conclusion, PDRN might be effective in promoting the healing of diabetic wounds in a murine model of STZ-induced diabetes.

Pien-tze-huang promotes wound healing in streptozotocin-induced diabetes models associated with improving oxidative stress via the Nrf2/ARE pathway.

Diabetic foot ulcers are a serious complication of diabetes, with high mortality and a lack of effective clinical treatment, which leads to a considerable financial burden. Pien-Tze-Huang (PZH) is a Chinese traditional medicine with a long history that has been found to be an effective and convenient treatment for inflammatory diseases such as skin abscesses and ulcers. In this study, we assessed the effects of PZH on diabetic wounds and the underlying mechanisms. The wounds were established on the backs of streptozotocin-induced type 1 diabetic rats and type 2 diabetic mouse models. We found that PZH treatment used locally or by gavage significantly promoted wound healing, accelerated re-epithelialization and vasculature in the wound tissue, upregulated the expression of the growth factors VEGF-A, PDGF, and EGF, and activated the Nrf2/ARE pathway in the wound tissue. In vitro assays showed that PZH improved the proliferation, migration and angiogenic function of human umbilical vein endothelial cells (HUVECs) cultured in palmitic acid, reduced the expression of the apoptotic proteins p53, Bax, and cleaved-caspase3, and activated Nrf2/ARE signaling; however, these protective effects were abrogated after Nrf2 was knocked down by specific siRNA. In addition, the levels of the serum inflammatory cytokines IL-1β, TNF-α, and IL-6 were reduced after PZH gavage treatment. In conclusion, the positive role of PZH in diabetic wound healing might be related to the activation of the Nrf2/ARE pathway to regulate the level of oxidative stress in vivo and increase the expression of growth factors to improve angiogenesis.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.

Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice.

Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations. The level of atypical DNA comets on day 21 after a single administration of streptozotocin increased in the kidneys, but not in the brain, testes, and pancreas. Real-time PCR revealed mtDNA damage in the liver, kidney, and pancreatic cells of mice with streptozotocin-induced diabetes. Thus, these animal models were found to reproduce pathognomic signs of diabetes, hyperglycemia, and nDNA damage; mtDNA damage was also detected.

The Potential Protective Role of Neoeriocitrin in a Streptozotocin-Induced Diabetic Model in INS-1E Pancreatic ß-Cells

HIGHLIGHTS The potential protective effect of Neo in the STZ-induced damage in INS-1E cells was evaluated. The protective role of Neo on cell viability and reactive oxygen species formation were evaluated. Neo prevented ROS formation and elevated insulin levels in high glucose conditions. Pretreatment of Neo might be a candidate agent to prevent ROS in STZ-induced diabetes.

Dose-dependent effects of taurine against testicular damage in a streptozotocin-induced type 1 diabetes mellitus rat model.

Testicular dysfunction has been associated with chronic hyperglycemia in diabetes mellitus patients. We investigated taurine's possible mechanisms and protective effects against testicular damage using a rat model of streptozotocin-induced diabetes. Wistar rats (N = 56) were divided into seven equal groups. Untreated control rats received saline, and treated control rats received taurine 50mg/kg orally. To induce diabetes, rats received a single dose of streptozotocin. Metformin-treated diabetic rats received metformin at a dose of 300mg/kg. Taurine-treated groups received 10, 25, or 50mg/kg. All treatments were provided orally once a day for 9weeks following the streptozotocin injection. Levels of blood glucose, serum insulin, cholesterol, testicular tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) were examined. Sperm count, progressive sperm motility, and sperm abnormalities were examined. Body and relative reproductive gland weights were assessed. Histopathological examinations of the testes and epididymis were performed. Metformin as well as taurine (in a dose-dependent manner) resulted in significant improvements in body and relative reproductive gland weights, blood glucose, serum cholesterol, and insulin levels, as well as cytokine and oxidative parameters. These findings were associated with significant improvement in sperm count, progressive sperm motility, sperm abnormalities, and histopathological lesions in the testes and epididymis. Taurine can potentially improve hyperglycemia, hypercholesterolemia, and testicular damage associated with diabetes mellitus, possibly by controlling inflammation and oxidative stress.

Study of hypoglycemic properties of «Glyphasonorm» tablets and «Glyphasolin» capsules on the streptozotocin-induced diabetic rat model

The risk of developing any complications of diabetes is significantly reduced by monitoring and correcting blood glucose levels and blood pressure, as well as by observing healthy lifestyle rules. Early detection and treatment of type 2 diabetes contribute to the prevention of disease progression and the development of complications.&#x0D; The aim is to study the hypoglycemic effect of «Glyphasonorm» tablets and «Glyphasolin» capsules in a rat model of streptozotocin-induced diabetes.&#x0D; Materials and methods. The studies were carried out on Wistar rats injected intraperitoneally with nicotinamide at a dose of 230 mg/kg 15 minutes before intravenous injection of streptozotocin at a dose of 65 mg/kg. The dynamics of body weight of rats, glucose and glycosylated haemoglobin levels under the impact of long-term administration of metformin, «Glyphasonorm» tablets and «Glyphasolin» capsules were investigated.&#x0D; Results and discussion. The studies on a streptozotocin-induced diabetic model have established that under the action of «Glyphasonorm» tablets and «Glyphasolin» capsules, the level of glycosylated haemoglobin, which decreased along with the level of glucose in the blood of animals, was significantly reduced in comparison with diabetic control. After 14 days of research, the "Glyphasolin" capsules showed more pronounced hypoglycemic activity (4.4 % and 8.0 % more) than the "Glyphasonorm" tablets and the reference drug metformin. The «Glyphasolin» capsules on the 12th day of the study showed a marked decrease in glycosylated haemoglobin in the blood of animals (3.1 % and 5.6 % more) than the «Glyphasonorm» tablets and metformin.&#x0D; Conclusions. In the experimental model of streptozotocin diabetes in rats, "Gliphasolin" capsules showed a more pronounced hypoglycemic effect, which was manifested by a decrease in the content of glycosylated haemoglobin in the blood and prevailed over the effect of the comparative drug metformin and "Gliphasonorm" tablets.&#x0D; «Glyphasolin» capsules and «Glyphasonorm» tablets based on bioflavonoid complex from bean show promise in the treatment of type 2 diabetes on the background of obesity and reducing the risk of micro- and macroangiopathy

Validation of Antidiabetic and Antihyperlipidemic Effects of 80% Methanolic Extract of the Lonchocarpus laxiflorus Leaves in Streptozotocin-Induced Diabetic Swiss Albino Mice.

Diabetes mellitus (DM) is a chronic endocrine disorder that requires long-term treatment. In Ethiopian traditional medicine practice, plants have been provided with a vital role in fighting human and animal diseases since ancient times. The aqueous extract of Lonchocarpus laxiflorus (L. laxiflorus) leaves has been consumed for treating diabetes mellitus without confirming its safety and efficacy scientifically. This experiment aimed to evaluate the safety and antidiabetic efficacy of the leaf extract of L. laxiflorus in mice models. The crude extraction was conducted using a cold maceration technique and 80% methanol solvent. Normoglycemic, oral glucose-loaded, and streptozotocin-induced (STZ) diabetic models were employed. Male Swiss albino mice were randomly grouped into five categories( with six mice per group during normoglycemic, oral glucose-loadingtest as a negative control, positive control, and three treatment groups. In STZ-induced diabetic models, the groups include normal and diabetic negative control, diabetic positive control, and three diabetic treatment groups. The negative control groups received vehicles, the positive control received 5 mg/kg glibenclamide, and the treatment groups received the crude extract at 100, 200, and 400 mg/kg doses, respectively. Up to 2000 mg/kg crude extract, neither signs of toxicity nor death were observed. In normoglycemic mice, there was a significant blood glucose reduction at 200 and 400 mg/kg doses starting from the 2nd h post-administration. The oral glucose load showed a significant antihyperglycemic effect at 200 and 400 mg/kg of the crude extract and glibenclamide. In STZ-induced diabetic models, the 200, 400 mg/kg crude extract, and glibenclamide showed a significant antidiabetic activity and enhancement of a good serum lipid profile. This study confirmed that the leaf of L. laxiflorus was safe and possesses antidiabetic and antidyslipidemic activities.

Ameliorating effects of mesenchymal stem cells on testicular injury in a prepubescent male rat model of streptozotocin-induced diabetes

Ameliorating effects of mesenchymal stem cells on testicular injury in a prepubescent male rat model of streptozotocin-induced diabetes

Upregulation of Antioxidative Gene Expression by Lasia spinosa Organic Extract Improves the Predisposing Biomarkers and Tissue Architectures in Streptozotocin-Induced Diabetic Models of Long Evans Rats.

Plants are an entity essential to the function of the biosphere as well as human health. In the context of human health, this research investigated the effect of Lasia spinosa (Lour) leaf methanolic extracts (LSML) on antioxidative enzymes and gene expression as well as biochemical and histological markers in a streptozotocin (STZ)-induced diabetes model. Fructose-fed streptozotocin (STZ)-induced diabetic animals were subjected to a four-week intervention followed by the assessment of the animal's blood and tissues for enzymatic, biochemical, histological, and genetic changes. LSML-treated groups were shown to decrease plasma glucose levels and improve body and organ weights compared to the untreated group in a dose-dependent manner. At the doses of 125 and 250 mg/kg b.w., LSML were able to normalize serum, hepatic, and renal biochemical parameters and restore the pancreas, kidney, liver, and spleen tissue architectures to their native state. A considerable increase (p &lt; 0.01) of liver antioxidant enzymes CAT, SOD, GSH, and a decrease of MDA level in LSML-treated groups were found at higher doses. The improved mRNA expression level of antioxidant genes CAT, SOD2, PON1, and PFK1 was also found at the doses of 125 mg/kg and 250 mg/kg BW when compared to untreated control groups. The results demonstrate that LSML impacts the upregulation of antioxidative gene expressions, thus improving the diabetic complications in animal models which need to be affirmed by compound-based antioxidative actions for therapeutic development.

Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes.

Natural biometabolites of plants have been reported to be useful in chronic diseases including diabetes and associated complications. This research is aimed to investigate how the biometabolites of Lasia spinosa methanol stem (MEXLS) extract ameliorative diabetes and diabetes-related complications. MEXLS was examined for in vitro antioxidant and in vivo antidiabetic effects in a streptozotocin-induced diabetes model, and its chemical profiling was done by gas chromatography-mass spectrometry analysis. The results were verified by histopathological examination and in silico ligand-receptor interaction of characterized natural biometabolites with antidiabetic receptor proteins AMPK (PDB ID: 4CFH); PPARγ (PDB ID: 3G9E); and mammalian α-amylase center (PDB ID: 1PPI). The MEXLS was found to show a remarkable α-amylase inhibition (47.45%), strong antioxidant action, and significant (p &lt; 0.05) decrease in blood glucose level, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein (LDL), urea, uric acid, creatinine, total cholesterol, triglyceride (TG), liver glycogen, creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase in serum insulin, glucose tolerance, and high-density lipoprotein (HDL). Rat's pancreas and kidney tissues were found to be partially recovered in histopathological analyses. Methyl α-d-galactopyranoside displayed the highest binding affinity with AMPK (docking score, -5.764), PPARγ (docking score, -5.218), and 1PPI (docking score, -5.615) receptors. Data suggest that the MEXLS may be an exciting source to potentiate antidiabetic activities affirming a cell-line study.

Impact of atorvastatin on plasma and cardiac biomarkers of inflammation, oxidative stress, and fibrosis in a rat model of streptozotocin-induced diabetes.

Oxidative stress and fibrosis foster the development of cardiovascular disease (CVD) in diabetes. Atorvastatin protects against cardiovascular diseases in diabetes patients. However, the mechanisms are not completely known. This study evaluated the impact of atorvastatin on vascular and myocardial oxidative stress, inflammation, and fibrosis in a model of diabetes. Male Wistar rats were assigned into four groups; control rats, atorvastatin-treated rats (Ator, 40mg/kg given by oral gavage for 6weeks), diabetes rats (DM, single IP 40mg/kg streptozotocin), and diabetes rats treated with atorvastatin (DM + Ator). Serum and cardiac inflammatory, oxidant, and fibrotic markers were measured. Cardiac fibrosis was evaluated by Masson trichrome stain. Streptozotocin-induced diabetes as documented by the marked elevation in blood glucose. Levels of oxidant biomarkers of serum and cardiac nitrite, cardiac nitrate, and cardiac thiobarbituric acid reactive substances (TBARS) were increased in the DM group. The use of atorvastatin reduced nitrite and TBARS levels. Serum and cardiac inflammatory factors of endothelin-1 (ET-1) were elevated in the DM group, and the use of atorvastatin reduced these increases. Cardiac C-reactive protein tended to increase in the DM group and the use of atorvastatin reduced its level. Cardiac interstitial fibrosis was increased in the DM group with a parallel increase in the platelet-derived growth factor level. The use of atorvastatin reduced cardiac fibrosis. Diabetes was associated with an increase in serum and/or myocardial markers of oxidative stress, inflammation, and fibrosis. The use of atorvastatin reduced cardiac interstitial fibrosis and decreased cardiac oxidant and inflammatory biomarkers.

In Vivo Treatment with a Standardized Green Tea Extract Restores Cardiomyocyte Contractility in Diabetic Rats by Improving Mitochondrial Function through SIRT1 Activation.

Background. Green tea catechins are known to promote mitochondrial function, and to modulate gene expression and signalling pathways that are altered in the diabetic heart. We thus evaluated the effectiveness of the in vivo administration of a standardized green tea extract (GTE) in restoring cardiac performance, in a rat model of early streptozotocin-induced diabetes, with a focus on the underlying mechanisms. Methods. Twenty-five male adult Wistar rats were studied: the control (n = 9), untreated diabetic animals (n = 7) and diabetic rats subjected to daily GTE administration for 28 days (n = 9). Isolated ventricular cardiomyocytes were used for ex vivo measurements of cell mechanics and calcium transients, and molecular assays, including the analysis of functional protein and specific miRNA expression. Results. GTE treatment induced an almost complete recovery of cardiomyocyte contractility that was markedly impaired in the diabetic cells, by preserving mitochondrial function and energy availability, and modulating the expression of the sarcoplasmic reticulum calcium ATPase and phospholamban. Increased Sirtuin 1 (SIRT1) expression and activity substantially contributed to the observed cardioprotective effects. Conclusions. The data supported the hypothesis that green tea dietary polyphenols, by targeting SIRT1, can constitute an adjuvant strategy for counteracting the initial damage of the diabetic heart, before the occurrence of diabetic cardiomyopathy.

Dehydrozingerone promotes healing of diabetic foot ulcers: a molecular insight.

One of the most common problems of diabetes are diabetic foot ulcers (DFUs). According to National Institute for Health, initial management of DFUs can decrease the complication of limb amputations and can improve the patient's quality of life. DFU treatment can be optimized with the help of multidisciplinary approach. Based on many studies, control of glucose levels in blood, antioxidant activity, reduction in cytokine levels, re-epithelialization, collagen formation, migration of fibroblasts are major phases involved in managing DFU. Dehydrozingerone (DHZ), has been known for its anti-inflammatory, antioxidant and wound healing properties. Three months high-fat dietand low dose of streptozotocin-induced type-II diabetic foot ulcer model was used to evaluate the effectiveness of dehydrozingerone. DHZ was given orally to rats for 15days post wounding. TNF-α, IL-1β and antioxidant parameters like lipid peroxidation, glutathione reductase were estimated. Immunoblotting was done to investigate the effect of DHZ on the expression of ERK, JNK, HSP-27, P38, SIRT-1, NFκB, SMA, VEGF andMMP-9 in skin tissue. Histopathology was performed for analyzing DHZ effect on migration of fibroblasts, formation of epithelium, granulation tissue formation, angiogenesis and collagen formation. DHZ decreased the levels of malondialdehyde, TNF-α, IL-1β and increased glutathione levels in wound tissue. Western blotting results suggested that DHZ activated ERK1/2/JNK/p38 signaling, increased expression of HSP-27, SIRT-1, VEGF, SMA thus facilitating the migration and proliferation of fibroblasts, angiogenesis and decreased inflammation. Masson Trichrome & histopathology showedan increase in collagen, epithelial and granulation tissue formation. DHZ significantly accelerates the healing of diabetic foot ulcers in high fat diet fed pluslow dose streptozotocin induced type-II diabetic Wistar rats.

Comparing Extracorporeal Shockwave and Hyperbaric Oxygen Therapy in Enhancing Wound Healing in a Streptozotocin-Induced Diabetic Rodent Model

Comparing Extracorporeal Shockwave and Hyperbaric Oxygen Therapy in Enhancing Wound Healing in a Streptozotocin-Induced Diabetic Rodent Model

Evaluation of in vivo Antidiabetic, Antidyslipidemic and in vitro Anti-Oxidant Activity of Extract and Solvent Fractions of Discopodium penninervum Hoschst Leaf in Mice: Normoglycemic and Streptozocin-Induced Model.

Diabetes mellitus has become a huge global public health and economic issue. The shortcomings of current medicines, as well as their serious side effects, prompted a focused quest for natural medicinal agents. In Ethiopia, the leaf of Discopodium penninervum Hoschst has been utilized in the traditional health system to treat diabetes. The goal of this study was to confirm the anti-diabetic, anti-dyslipidemia, and anti-oxidant activity of Discopodium penninervum Hoschst leaf in both in vitro and in vivo. In the normoglycemic, glucose-loaded, and streptozotocin-induced diabetic mouse models, the blood glucose-lowering effects of extract and solvent fractions of the leaf of Discopodium penninervum Hoschst were tested. The weight and lipid profile of streptozotocin-induced diabetic mice were assessed after treatment with leaf extract and solvent fractions for 14 days. The DPPH test was used to assess the antioxidant activity of the plant leaf extract. In the normoglycemic model and glucose loaded test, the leaf extract of Discopodium penninervum Hoschst demonstrated significant blood glucose decrease (34.1%, p<0.001) and 44.5%, p<0.001, respectively, when compared to the normal control. When compared to a diabetic control group, extract and solvent fractions significantly (p<0.001) reduced blood glucose levels on the 14th day in the streptozotocin-induced diabetic model. In addition, serum TC, STG, TG, LDL, and VLDL levels were reduced significantly (p<0.001). IC50 values of leaf extract and a standard medication (ascorbic acid) in the antioxidant activity test were 4.1g/mL and 10.23g/mL, respectively. The hydro-alcoholic leaf extract and solvent fractions of Discopodium penninervum Hoschst leaves have demonstrated blood glucose-lowering effect, which justify ethnobotanical use, and can therefore be used as a good insight for new anti-diabetic medication source with a call for additional studies.

Potential of phthalocyanine on streptozotocin-induced diabetic rats: An initiative of dye in substitution of therapeutics

Type 1 diabetes mellitus, is one of the severe chronic metabolic diseases with severe worldwide complications due to increased levels of glucose affecting many organ functionalities. Antioxidant properties reduce the free radicals and inhibit the oxidation that promotes cellular development in many conditions such as diabetes, Alzheimer’s disease and cardiovascular disorders. Phthalocyanine is a large blue colored aromatic compound with high potential of anti-oxidant ability owing to the presence of porphyrazine ring units. The present study has aimed at examining the potential effect of phthalocyanine on the streptozotocin-induced diabetic model over 28 days. For the study, the animals were assigned into 4 groups: control, diabetic, phthalocyanine (10 [Formula: see text]g/kg/day) treated diabetic group and phthalocyanine (20 [Formula: see text]g/kg/day) treated diabetic group. After the induction of diabetes using streptozotocin (53 mg/kg body weight), phthalocyanine (10 [Formula: see text]g/kg/day) and phthalocyanine (20 [Formula: see text]g/kg/day) were given daily for 28 days and the blood glucose level was checked on 7th, 14th, 21st and 28th day. A significant reduction in blood glucose within the period on the 28th day with increase in body weight was observed. Phthalocyanine also showed a decrease in the total protein content and blood urea nitrogen with improved oxidative stress parameters. The histopathological analyses displayed improvement in pancreatic structure with basal rounded nuclei and well-defined boundaries normal acini with a phthalocyanine dose (10 [Formula: see text]g/kg). It was concluded that phthalocyanine at the dose of 10 [Formula: see text]g/kg presented anti-diabetic and anti-hyperlipidemic actions with protective effect to the pancreatic [Formula: see text]-cell within 28 days.

Effect of Chronic Treatment with Uridine on Cardiac Mitochondrial Dysfunction in the C57BL/6 Mouse Model of High-Fat Diet-Streptozotocin-Induced Diabetes.

Long-term hyperglycemia in diabetes mellitus is associated with complex damage to cardiomyocytes and the development of mitochondrial dysfunction in the myocardium. Uridine, a pyrimidine nucleoside, plays an important role in cellular metabolism and is used to improve cardiac function. Herein, the antidiabetic potential of uridine (30 mg/kg/day for 21 days, i.p.) and its effect on mitochondrial homeostasis in the heart tissue were examined in a high-fat diet–streptozotocin-induced model of diabetes in C57BL/6 mice. We found that chronic administration of uridine to diabetic mice normalized plasma glucose and triglyceride levels and the heart weight/body weight ratio and increased the rate of glucose utilization during the intraperitoneal glucose tolerance test. Analysis of TEM revealed that uridine prevented diabetes-induced ultrastructural abnormalities in mitochondria and sarcomeres in ventricular cardiomyocytes. In diabetic heart tissue, the mRNA level of Ppargc1a decreased and Drp1 and Parkin gene expression increased, suggesting the disturbances of mitochondrial biogenesis, fission, and mitophagy, respectively. Uridine treatment of diabetic mice restored the mRNA level of Ppargc1a and enhanced Pink1 gene expression, which may indicate an increase in the intensity of mitochondrial biogenesis and mitophagy, and as a consequence, mitochondrial turnover. Uridine also reduced oxidative phosphorylation dysfunction and suppressed lipid peroxidation, but it had no significant effect on the impaired calcium retention capacity and potassium transport in the heart mitochondria of diabetic mice. Altogether, these findings suggest that, along with its hypoglycemic effect, uridine has a protective action against diabetes-mediated functional and structural damage to cardiac mitochondria and disruption of mitochondrial quality-control systems in the diabetic heart.

Melatonin prevents diabetes-induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction.

Impaired nutrient sensing mechanisms such as AMPK/silent information regulator type 1 (SIRT1) axis and autophagy in renal cells upon chronic diabetic condition accelerate renal injury and upregulating these mechanisms has been reported to prevent renal damage. Melatonin, a neuroendocrine agent, also possess antioxidant and AMPK modulatory effect. In the current study, the protective effect of melatonin against diabetic renal injury was assessed in streptozotocin-induced diabetic nephropathy model and in in vitro model of high-glucose-induced tubular injury. Melatonin (3 and 10 mg/kg) was administered for 28 days after 4 weeks of diabetes induction in Sprague-Dawley rats. For in vitro model, the NRK-52E cells were co-incubated with high glucose and melatonin (25 and 50 μM). Melatonin supplementation abrogated the diabetes-induced renal injury and improved renal function in diabetic rats. Immunoblot analysis of renal tissue lysates revealed improved expression of AMPK, as well as upregulated the expression of nuclear factor erythroid 2-related factor 2, SIRT1, PGC-1α, TFAM and enhanced autophagy upon melatonin treatment in diabetic rats. Likewise, melatonin treatment in high glucose exposed NRK-52E cells improved expression of AMPK, enhanced mitochondrial biogenesis and positively modulated autophagy. However, these effects were repressed upon inhibition of AMPK activity in NRK-52E cells by treatment of Compound-C, suggesting that the protective effects of melatonin were mainly mediated through activation of AMPK. These results suggest that melatonin might mediate the renoprotective effect by upregulating the AMPK/SIRT1 axis, enhancing the autophagy and mitochondrial health in DIabetic Nephropathy.