scholarly journals Keratinocytes differentiation and wound healing in rats with streptozotocin – induced diabetes and severe hyperglycemia

2020 ◽  
Vol 23 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Evgeniy V. Ivanov ◽  
Maria P. Morozova ◽  
Ekaterina M. Rzhavina ◽  
Anna M. Gorbacheva ◽  
Svetlana A. Gavrilova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Its Region ◽  
Repair Process ◽  
Diabetic Rat ◽  
Control Group ◽  
Intact Skin ◽  
Skin Repair ◽  
Diabetes Model ◽  
Streptozotocin Induced Diabetes

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing. AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model. MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17. RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds. CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation.

scholarly journals Wound healing mechanisms in rats with streptozotocin-induced diabetes mellitus

2018 ◽  
Vol 64 (5) ◽  
pp. 292-298
Author(s):  
Evgeniy V. Ivanov ◽  
Svetlana A. Gavrilova ◽  
Maria P. Morozova ◽  
Ekaterina M. Klochihina ◽  
Aleksey K. Erdyakov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Tissue Repair ◽  
Control Group ◽  
Withdrawal Time ◽  
Diabetes Group ◽  
Citrate Buffer ◽  
Ki 67 ◽  
Streptozotocin Induced Diabetes ◽  
Β2 Adrenoreceptors

Background. Wound healing disorders and formation of diabetic foot, a severe disabling complication of diabetes mellitus, are accompanied by nervous system impairment and/or ischemia. Objective — the study was aimed at assessing the effect of peripheral innervation disorders on the regulation of tissue repair in the streptozotocin-induced rat model of diabetes mellitus. Material and methods. The study was carried out in male white outbred rats (n=70). The animals were wounded 42 days after induction of diabetes by injecting streptozotocin (diabetes group; this group received insulin Levemir at a dose of 2 units/kg in saline subcutaneously to reduce mortality), or after injection of citrate buffer (CB group). Skin samples were taken on day 8, 16, and 24 after wound modeling. Pain sensitivity was assessed in all animals. The resulting skin fragments were fixed, dehydrated, and embedded in paraffin according to standard procedures. Sections were stained with hematoxylin and eosin, antibodies specific for Ki-67, α1, β1, and β2-adrenoreceptors were used for immunohistochemical staining. Intact animals were used as an additional control group. Results. Tail withdrawal time measured on day 56 was higher in DM group rats as compared to the control group (p=0.017). CB group demonstrated a tendency towards more rapid wounds healing than diabetic animals, although the difference was not statistically significant due to wide scatter of data in the DM group (p=0.64). The intensity of staining for Ki67 was lower in the DM group (p=0.045). Reduced density of β2-adrenoreceptors was observed at the areas remote from the wound in CB group rats. Conclusion The results show no correlation between altered innervation and impaired tissue repair in rats with streptozotocin-induced diabetes.

scholarly journals The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats

2017 ◽  
Vol 95 (11) ◽  
pp. 1343-1350
Author(s):  
Aleksandra Vranic ◽  
Stefan Simovic ◽  
Petar Ristic ◽  
Tamara Nikolic ◽  
Isidora Stojic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systolic Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Albino Rats ◽  
Acute Administration ◽  
Rat Hearts ◽  
Patients With Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Wistar Albino Rats

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

scholarly journals Diabetes mellitus increased integrins gene expression in rat endometrium at the time of embryo implantation

2019 ◽  
Author(s):  
Abbas Bakhteyari ◽  
Yasaman Zarrin ◽  
Parvaneh Nikpour ◽  
Zeinab Sadat Hosseiny ◽  
Zeinab Sadat Hosseiny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Group Treatment ◽  
Embryo Implantation ◽  
Treated Group ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Genes Expression ◽  
Normal Menstrual Cycle

Background: Diabetes mellitus deeply changes the genes expression of integrin (Itg) subunits in several cells and tissues such as monocytes, arterial endothelium, kidney glomerular cells, retina. Furthermore, hyperglycemia could impress and reduce the rate of successful assisted as well as non-assisted pregnancy. Endometrium undergoes thorough changes in normal menstrual cycle and the question is: What happens in the endometrium under diabetic condition? Objective: The aim of the current study was to investigate the endometrial gene expression of α3, α4, αv, Itg β1 and β3 subunits in diabetic rat models at the time of embryo implantation. Materials and Methods: Twenty-eight rats were randomly divided into 4 groups: control group, diabetic group, pioglitazone-treated group, and metformin-treated group. Real-time PCR was performed to determine changes in the expression of Itg α3, α4, αv, β1, and β3 genes in rat’s endometrium. Results: The expression of all Itg subunits increased significantly in diabetic rats’ endometrium compared with control group. Treatment with pioglitazone significantly reduced the level of Itg subunits gene expression compared with diabetic rats. While metformin had a different effect on α3 and α4 and elevated these two subunits gene expression. Conclusion: Diabetes mellitus significantly increased the expression of studied Itg subunits, therefore untreated diabetes could be potentially assumed as one of the preliminary elements in embryo implantation failure.

scholarly journals EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS

2020 ◽  
Vol 33 (1) ◽  
Author(s):  
Letícia Fuganti CAMPOS ◽  
Eliane TAGLIARI ◽  
Thais Andrade Costa CASAGRANDE ◽  
Lúcia de NORONHA ◽  
Antônio Carlos L. CAMPOS ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Type I Collagen ◽  
Chronic Wounds ◽  
Skin Wound ◽  
Diabetic Rats ◽  
Control Group ◽  
Type I ◽  
Collagen Deposition ◽  
Skin Wound Healing

ABSTRACT Background: Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

scholarly journals Enhancement of Liver Toxicity on Diabetes Mellitus by a Universal Chemical Pollutant (Acrylonitrile) in Rats

2019 ◽  
Vol 26 (2) ◽  
pp. 9-17
Author(s):  
Sameer E. Alharthi
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Aqueous Solution ◽  
Liver Toxicity ◽  
Elevated Serum ◽  
Diabetic Rat ◽  
Control Group ◽  
Distilled Water ◽  
Serum Aminotransferase ◽  
Cyp2e1 Activity

The present study was designed to investigate potential liver damage due to acrylonitrile in Streptozotocin induced diabetes in rats. Twenty-four rats were divided into 4 treatment groups. Nondiabetic control rat receiving distilled water, non-diabetic rat receiving acrylonitrile aqueous solution (10 mg/kg/day), diabetic control rat receiving distilled water and diabetic rat receiving acrylonitrile aqueous solution. All groups received the treatment for 4 weeks. The animals were assessed for hepatoxicity markers in serum, oxidative stress markers, CYP2E1 activity and cyanide formation in tissues. Acrylonitrile significantly elevated serum aminotransferase, alanine aminotransferase, total bilirubin levels, triglycerides and total cholesterol in diabetic groups as compared to normal control group. Antioxidant markers like glutathione showed significant decline while a significant increase in malondialdehyde, superoxide dismutase and catalase in diabetic rats treated with acrylonitrile. CYP2E1 activity was observed in acrylonitrile – exposed nondiabetic and diabetic groups as compared to control. Cyanide formation was raised in both the nondiabetic and diabetic groups as compared to control group. Acrylonitriles can produce acute hepatic injury, induction of diabetes mellitus type II, and accomplish the CYP2E1 enzyme which sequentially leads to generation of oxidative stress and its metabolic product–cyanide that may potentiate the oxidative stress posing more deleterious effect.

Composite sponges from sheep decellularized small intestinal submucosa for treatment of diabetic wounds

2020 ◽  
pp. 088532822096389
Author(s):  
Gamze Kara Magden ◽  
Cigdem Vural ◽  
Busra Yaprak Bayrak ◽  
Candan Yilmaz Ozdogan ◽  
Halime Kenar
Keyword(s):  
Wound Healing ◽  
Hyaluronic Acid ◽  
Rat Model ◽  
Small Intestinal Submucosa ◽  
Diabetic Rat ◽  
Control Group ◽  
Significant Difference ◽  
Small Intestinal ◽  
Intestinal Submucosa ◽  
Diabetic Rat Model

Despite the fast development of technology in the world, diabetic foot wounds cause deaths and massive economical losses. Diabetes comes first among the reasons of non traumatic foot amputations. To reduce the healing time of these fast progressing wounds, effective wound dressings are in high demand. In our study, sheep small intestinal submucosa (SIS) based biocompatible sponges were prepared after SIS decellularization and their wound healing potential was investigated on full thickness skin defects in a diabetic rat model. The decellularized SIS membranes had no cytotoxic effects on human fibroblasts and supported capillary formation by HUVECs in a fibroblast-HUVEC co-culture. Glutaraldehyde crosslinked sponges of three different compositions were prepared to test in a diabetic rat model: gelatin (GS), gelatin: hyaluronic acid (GS:HA) and gelatin: hyaluronic acid: SIS (GS:HA:SIS). The GS:HA:SIS sponges underwent a 24.8 ± 5.4% weight loss in a 7-day in vitro erosion test. All sponges had a similar Young’s modulus under compression but GS:HA:SIS had the highest (5.00 ± 0.04 kPa). Statistical analyses of histopathological results of a 12-day in vivo experiment revealed no significant difference among the control, GS, GS:HA, and GS:HA:SIS transplanted groups in terms of granulation tissue thickness, collagen deposition, capillary vessel formation, and foreign body reaction (P > 0.05). On the other hand, in the GS:HA:SIS transplanted group 80% of the animals had a complete epidermal regeneration and this was significantly different than the control group (30%, P < 0.05). Preclinical studies revealed that the ECM of sheep small intestinal submucosa can be used as an effective biomaterial in diabetic wound healing.

scholarly journals Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammad Ashafaq ◽  
Laxmi Varshney ◽  
Mohammad Haaris Ajmal Khan ◽  
Mohd. Salman ◽  
Mehar Naseem ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Rat ◽  
Limiting Factor ◽  
Enzymatic Antioxidants ◽  
Neuroprotective Effects ◽  
Once Daily ◽  
Stress Markers ◽  
Streptozotocin Induced Diabetes ◽  
Nonenzymatic Antioxidants

Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-) induced diabetes mellitus and its complication in central nervous system (CNS). Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65 mg/kg body weight). Three days after STZ injection, HP was given (50 mg/kg b.wt. orally) once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model.

scholarly journals Effect of Abelmoschus esculentus (okra)-based diet on streptozotocin-induced diabetes mellitus in adult Wistar rats

2020 ◽  
Vol 19 (8) ◽  
pp. 1737-1743
Author(s):  
Patrick O. Uadia ◽  
Isaac O. Imagbovomwan ◽  
Kelly Oriakhi ◽  
Ikechi G. Eze
Keyword(s):  
Diabetes Mellitus ◽  
Normal Control ◽  
Wistar Rats ◽  
Diabetic Control ◽  
Normal Diet ◽  
Abelmoschus Esculentus ◽  
Control Group ◽  
Β Cells ◽  
Streptozotocin Induced Diabetes ◽  
Ad Libitum

Purpose: To evaluate the effects of an okra-based diet on streptozotocin-induced diabetes mellitus in adult Wistar rats and its mechanism of action.Methods: Wistar rats (6) were administered streptozotocin (50 mg/kg ip) after an overnight fast. Upon confirmation of diabetes mellitus, the animals were fed ad libitum for 21 days with formulated okrabased test diet in place of normal diet. The rats treated similarly with streptozotocin and fed ad libitum with the normal diet served as diabetic control while rats fed on normal diet and not treated with streptozotocin served as the negative control. Thereafter, the rats were sacrificed, fasting bloodcollected and analysed for glucose concentration and biochemical parameters. Pancreas was also excised for histopathological studies.Results: There was a significant increase in body weight, HDL-cholesterol (p< 0.05) but significant decrease in blood glucose (p < 0.05), serum total cholesterol, triglyceride, LDL-cholesterol and VLDLcholesterol concentrations in the okra-fed diabetic treated rats when compared to the diabetic control group. Furthermore, superoxide dismutase activity (SOD) was significantly higher in the diabetic control, and reduced significantly when fed with okra-based diet (p < 0.05). Catalase (CAT) activity was significantly (p < 0.05) decreased in diabetic control and treated group, whereas it was significantly (p < 0.05) increased in normal control rats. There was a significant (p < 0.05) decrease in reduced glutathione levels. The significant (p< 0.05) increase in malondialdehyde in the diabetic group was significantly decrease in the diabetic rats fed with okra-diet. Also serum insulin level was significantly (p < 0.05) increased and serum α amylase activity was significantly (p < 0.05) decrease in the diabetic treated rats. Histology results show that there was damage to the β cells of the pancreas in the diabetic control when compared to normal control, but rats fed okra diet was able to regenerate endocrine β cells.Conclusion: Okra-based diet lowers hyperglycaemia as well as regenerate/repair endocrine β-cells and exocrine tissues of the pancreas damage by streptozotocin Keywords: Abelmoschus esculentus, Diabetes mellitus, anti-diabetic, Insulin, α-amylase, Mechanism

scholarly journals The influence of mildronate on peripheral neuropathy and some characteristics of glucose and lipid metabolism in rat streptozotocin-induced diabetes mellitus model

2011 ◽  
Vol 57 (5) ◽  
pp. 490-500 ◽  
Author(s):  
J. Sokolovska ◽  
J. Rumaks ◽  
N. Karajeva ◽  
D. Grinvalde ◽  
J. Sharipova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Neuropathic Pain ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Tolerance Test ◽  
Diabetic Rat ◽  
Oral Glucose ◽  
Glucose And Lipid Metabolism ◽  
Glucose Ingestion ◽  
Streptozotocin Induced Diabetes

Streptozotocin (STZ) was used to induce the diabetic rat model. STZ rats were treated with mildronate (100 mg/kg daily, per os or intraperitoneally for 6 weeks). Body weight, blood glucose, triglyceride, ketone body concentrations, glycated hemoglobin percent (HbA1c%), glucose tolerance, and the development of neuropathic pain were monitored throughout the experiment. In the STZ + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose (on week 4) and triglyceride concentrations (on weeks 3-6), significantly slowed the increase in HbA1c% (on week 6) and improved glucose tolerance 120 minutes after glucose ingestion during oral glucose tolerance test versus the STZ group. Mildronate completely protected development of STZ-induced neuropathic pain from the first administration week up to end of the experiment. The obtained data indicate clinical usefulness of the drug for the treatment of diabetes mellitus and its complications.

scholarly journals EFFECT OF THE ENZYME-CONTAINING POLYMERIC NANOPARTICLES ON MMP-2 ACTIVITY DURING BURN WOUND HEALING IN RATS WITH STREPTOZOTOCIN-INDUCED DIABETES

2021 ◽  
Vol 17 (2) ◽  
pp. 12-19
Author(s):  
O.I. Myronenko ◽  
T.I. Panova ◽  
L.V. Natrus ◽  
S.V. Verevka
Keyword(s):  
Diabetes Mellitus ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Gelatin Zymography ◽  
Matrix Metalloproteinase 2 ◽  
Diabetic Wound ◽  
Burn Wound ◽  
Impaired Wound Healing ◽  
Chronic Hyperglycemia ◽  
Streptozotocin Induced Diabetes

Relevance. Diabetic foot syndrome is a common complication that is characterized by the development of chronic ulcers. Among the mechanisms of impaired wound healing, the leading role is played by disturbance of extracellular matrix homeostasis: chronic hyperglycemia, on the one hand, promotes the formation of so-called advanced glycation end products (AGEs), which mediate pro-inflammatory activation of immune cells, and on the other hand, inhibits fibroblasts proliferation and collagen production, disrupts the migration of keratinocytes and endothelial cells. Therefore, the elimination of AGEs is a pathogenetic approach in diabetic wound treatment. For this purpose, a composite consisting of polyspecific microbial proteinases fixed on polymeric porous nanoparticles was developed. The activity of matrix metalloproteinase-2 (MMP-2) was chosen as a prognostic indicator of chronic wound healing. Objective: to study the activity of MMP-2 in the tissues of the burn wound of rats with simulated diabetes mellitus under the influence of enzyme-containing nanoparticles. Materials and methods. N = 48 Wistar rats were used in the experiment. Diabetes mellitus was induced by administration of 50 mg/kg of streptozotocin. To model the wound in rats, a standard animal model of thermal burns by Walker and Mason was used. Thermal damage corresponded to the II-IIIA degree of burns, and occupied 19±1.6% of the total area of ​​animal skin. Rats were divided into two groups of 24 animals each: the DM group did not receive any treatment, and rats from the DM+T group were daily applied to the burn wound with the mentioned composite (enzyme-containing nanoparticles). Animals were removed from the experiment on days 3, 7, 14 and 21 of observation. The activity of MMP-2 in the tissues of the burn wound of diabetic rats was studied by gelatin zymography, expressed in arbitrary units (AU). Statistical data processing was performed in the software package SPSS Statistics Base, v.22 with Student and Scheffe tests. Results. The level of activity of MMP-2 in the tissues of the burn wound of rats in the DM group on the 3rd day of the study was 4.9 ± 1.3 AU, increased by 7 days (p <0.01) and reached a maximum level of 52.55 ± 3.06 AU at day 14 (p <0.01). On day 21, the activity of the test enzyme decreased by 8.5 AU (p <0.01), compared to day 14. On day 3 of the study in the DM+T group, the activity of MMP-2 in the diabetic wound was 15.93 ± 2.68 AU and gradually decreased (p <0.01) to 5.67 ± 2.67 AU on day 14. However, on day 21, the second peak (p <0.01) of the activity of the studied enzyme was observed - 33.64 ± 4.1 AU. When comparing the two groups (DmM and DM+T) on day 3 of the study, the activity of MMP-2 in the tissues of the burn wound of rats in the DM+T group was three times higher (p <0.01) than in the DM group. But from the 7th day the activity of MMP-2 in the DM group was higher than the DM+T group. On day 21 of the study, the level of MMP-2 in the DM group remained higher (p <0.01) than in the DM+T group. Conclusions. The use of enzyme-containing nanoparticles provides effective degradation of glycosylated components of the extracellular matrix (AGEs), thereby reducing the inflammatory process and activity of MMP-2, and promoting wound healing in rats with streptozotocin-induced diabetes.

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