Streptozotocin-induced Diabetic Rats Research Articles

Syringic Acid Alleviates Hyperglycemia by Regulating Hepatic Key Enzymes of Carbohydrate Metabolism in Streptozotocin-induced Diabetic Rats

Background: Diabetes mellitus is a complex metabolic disorder characterized by the development of hyperglycemia due to impaired insulin production, insulin action, or both. The persistent hyperglycemia associated with diabetes can lead to an increased risk of developing severe health problems. This study examines whether the bioactive phenolic compound Syringic Acid (SA) mitigates hyperglycemia in streptozotocin-induced diabetic rats. Materials and Methods: A total of 30 male Sprague-Dawley rats were utilized in the investigation, and they were split into five groups: Normal (N), Normal+Syringic Acid (N+SA), Diabetic Control (DC), Diabetic+Syringic Acid (D+SA), and Diabetic+Glimepiride (D+GM). A single dose of streptozotocin (40 mg/kg) injected intraperitoneally was used to induce diabetes. Syringic Acid (SA) was given orally once a day for 60 days at a dose of 50 mg/Kg body weight. The levels of plasma insulin, glucose, glycated haemoglobin, and the activity of carbohydrate metabolizing enzymes were examined. Results were compared with diabetic rats provided with the standard drug glimepiride (0.1 mg/kg). Results: Syringic acid treatment substantially lowered hyperglycemia, enhanced insulin levels, and lowered HbA1c, in diabetic rats when given at a dose of 50 mg/Kg body weight. Additionally, syringic acid exhibited the ability to considerably lower the activities of fructose 1,6-bisphosphatase and glucose-6 phosphatase while significantly increasing the activities of glycolytic enzymes like pyruvate kinase and hexokinase. Conclusion: These results imply that syringic acid could potentially attenuate hyperglycemia in streptozotocin-induced diabetic rats by modulating carbohydrate metabolism.

Peptide Hydrolysate of Telfairia occidentalis Hook f. Seed Protein Promotes Effective Glucose Homeostasis by Improving β-cell Dysfunction and Abating Carbohydrate Metabolic Disturbance in Diabetic Rats

Rising concerns with the use of synthetic antidiabetic drugs have promoted a shift towards the use of natural products. This study therefore investigated the antidiabetic activity of peptide hydrolysate of Telfairia occidentalis (T. occidentalis) seed protein (PHTOSP) in streptozotocin-induced diabetic rats. Thirty-six (36) experimental animals were randomly distributed into six groups (A–F) of six rats each (n = 6). Group A served as normal control while groups B, C, D, E, and F were treated with streptozotocin (STZ, 50 mg/kg body weight, b.w, i.p) dissolved in cold citrate buffer (0.1 M, pH 4.5) to induce type 2 diabetes. Groups C, D, and E were administered 50, 100, and 150 mg/kg b.w PHTOSP, respectively, while groups B and F were diabetic untreated and 5 mg/kg b.w glibenclamide-treated controls, respectively, in the experiment that lasted for 21 days. Subsequently, the analysis of biochemical parameters demonstrated a significant (p<0.05) increase in serum insulin, hepatic glycogen, hexokinase, and glucose-6-phosphate dehydrogenase activities, accompanied by a significant (p<0.05) reduction in fasting serum glucose, glucose-6-phosphatase, and fructose-1,6-bisphosphatase, along with an enhancement in relative body weight. Similarly, PHTOSP demonstrated a significant (p<0.05) improvement on high-density (HDL) and low-density (LDL) lipoproteins, triglyceride (TG), total cholesterol (TC), and atherogenic index (AI) significantly (p<0.05). In addition, histoarchitectural analysis revealed a reversal of congestion and proliferation of inflammatory cells in the pancreatic tissue following treatment with PHTOSP. Therefore, PHTOSP might possess potential antidiabetic properties such that it improves glycolytic pathway and promotes cell survival that are helpful in the management of diabetes mellitus (DM).

Changes in myelinated fibers in the hippocampus of streptozotocin-induced diabetic rats: a stereological investigation.

Diabetes causes cognitive impairment, and the hippocampus is important for long-term and permanent memory function. However, the mechanism of their interaction is still unclear. In this study, rat models of diabetes mellitus were generated by a single injection of streptozotocin (STZ). This study aims to explore the changes in myelinated fibers in the hippocampus of type 1 diabetic rats. The unbiased stereological methods and transmission electron microscopy were used to obtain the total volume of the hippocampus, the total volume of the myelin sheath, the total length of the myelinated nerve fibers, the distribution of the length with different diameters of the myelinated fibers, and the distribution of the length with different thickness of the myelin sheath. Stereological analysis revealed that, compared to that of the control group, the total myelinated fibers volumes and the total myelinated fibers length were decreased slightly, while the total volume and the thickness of myelin sheaths were significantly decreased in the diabetic group. Finally, when compared with the control group, the total length of myelinated fibers in the diabetes group was significantly reduced, with diameters ranging from 0.7 to 1.1 μm and thicknesses of myelin sheaths from 0.15 to 0.17 μm. This study provides the first experimental evidence by stereological means to demonstrate that myelinated nerve fibers may be the key factor in cognitive dysfunction in diabetes.

Changes and related factors of blood CCN1 levels in diabetic patients.

To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR). Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting. Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats. Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation.

Ameliorating effects of Astragalus maximus methanolic extract on inflammation and oxidative stress in streptozotocin-induced diabetic rats

Introduction: Recent studies have reported that Astragalus spp. can display various biological effects, e.g., anticancer, antioxidant, antimicrobial, neuroprotective, and hepatoprotective activities. Here we decided to assess the ameliorating effects of Astragalus maximus methanolic extract (AMME) on inflammation and oxidative stress in streptozotocin-induced diabetic rats. Methods: The dried aerial parts were extracted by maceration technique with 70% methanol. Diabetes was induced in rats via intraperitoneal injection of streptozotocin at 65 mg/kg. Diabetic rats orally received AMME at 75-30 mg/kg for 28 days. The serum levels of glucose, insulin, liver enzymes, bilirubin, creatinine (Cr), urea (Ur), triglyceride, and cholesterol, as well as the tissue levels of oxidant/antioxidant enzymes and pro-inflammatory cytokines were evaluated by the diagnostic kits. The level of α-amylase inhibition by AMME was also determined. Results: AMME (150 and 300 mg/kg) treatment significantly reduced (P<0.001) the serum levels of glucose, cholesterol, triglyceride, Cr, Ur, liver enzymes, and oxidative enzymes in diabetic rats. The tissue levels of antioxidant enzymes in diabetic rats treated with AMME (150 and 300 mg/kg) were significantly increased (P<0.01). Treatment of diabetic rats with either 150 or 300 mg/kg AMME for 28 days significantly reduced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in the pancreas. AMME inhibited α-amylase in a dose-dependent manner with an IC50 value of 18.1 μg/mL. Conclusion: This study showed that the oral administration of AMME in diabetic rats displayed a potent anti-diabetic activity through increasing insulin release and ameliorating effects on inflammation and oxidative stress; however, more investigations are desired to determine the action mechanism of the extract.

Astragalus adscendens extract shows antidiabetic effects through controlling oxidative stress, inflammation and apoptosis in streptozotocin-induced diabetic rats

Objective: To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats. Methods: In order to induce diabetes, rats intraperitoneally received streptozotocin at 65 mg/kg. Sixty adult male Wistar rats were allocated into six groups (10 rats per each) including the healthy control group, the diabetic group as well as the diabetic group treated with Astragalus adscendens methanolic extract at 50, 100, and 200 mg/kg per day or glibenclamide (0.6 mg/kg/day) for 28 d. The effects of Astragalus adscendens methanolic extract on the levels of glucose, insulin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, urea, uric acid, total protein, albumin, triglyceride, cholesterol, α-amylase, oxidant/antioxidant enzymes, and inflammatory cytokines were evaluated. Real time-PCR was also used for measuring the gene expression of caspase-3, Bcl2, and Bax. Results: The levels of glucose, cholesterol, triglyceride, creatinine, urea, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and malondialdehyde considerably declined (P<0.001) in diabetic rats after treatment with Astragalus adscendens methanolic extract especially at a dose of 200 mg/kg. In addition, treatment with Astragalus adscendens methanolic extract noticeably increased the level of insulin, total protein, and albumin as well as improved the activities of catalase, glutathione peroxidase, and superoxide dismutase, as well as the expression levels of TNF-α, IL-1β, caspase-3, Bcl2 and Bax (P<0.001) compared to the diabetic control group. The extract also inhibited α-amylase in a dose-dependent manner with an IC50 value of 19.6 µg/mL. Conclusions: Astragalus adscendens methanolic extract shows potent antidiabetic, anti-inflammatory, anti-apoptotic, and antioxidant effects in diabetic rats. However, more studies are needed to verify the underlying mechanism of the effect of this plant extract and test its efficacy in clinical trials.

Antidiabetic Effect of Star Anise (Illicium verum) in Streptozotocin-induced Diabetic Rats.

The current study aimed to evaluate the antidiabetic potential of Illicium verum fruits. Illicium verum fruits are frequently used by the Moroccan population in the treatment of diabetes. The antihyperglycemic effect of the aqueous extract of Illicium verum fruits (AEIVF) in rats was assessed. The effects of AEIVF (20 mg/kg) on glycemia and lipid profile as well as its phytochemical and antioxidant properties were evaluated. In normal and diabetic rats, AEIVF reduced blood glucose levels 6 hours after administration. Furthermore, after 7 days of treatment, glycemia was lowered in diabetic rats, and this extract exhibited an antioxidant activity. The study shows that Illicium verum possesses a potent antidiabetic activity. In addition, the toxicity of AEIVF was evaluated and the LD50 value was found to be greater than the 2 g/kg dose.

Antidiabetic and antioxidant effect of magnetic and noble metal nanoparticles of Clitoria ternatea

Diabetes is a chronic metabolic endocrine disorder associated with diabetic complications that result in microvascular and macrovascular complications due to oxidative stress, neurodegeneration, and peripheral cell damage. Oxidative stress is characterized by the development of reactive oxygen species (ROS) which progresses by hampering antioxidant enzyme activities. Phytomolecules from different plant sources like leaves, flowers, fruits, etc are reported to possess super-antioxidant properties. Hence these phytomolecules can be good leads in the treatment and management of diabetes. Metal nanoparticles have evolved to increase the potency, efficacy, and safety of different drug delivery systems owing to their superior physicochemical properties. This research work is designed for the synthesis of magnetic and noble metal nanoparticles by green synthesis of fresh flower aqueous extract of Clitoria ternatea. A mechanistic evaluation of the magnetic (cobalt oxide) and noble metal (gold) nanoparticles has been designed by in-vitro and in-vivo models of a streptozotocin-induced diabetes model. The cobalt oxide and gold nanoparticles showed a significant (p < 0.05) decrease in the diabetic enzyme levels (α-amylase, α-glucosidase, and xanthine oxidase). In vitro and in vivo studies of the antioxidant activity of both nanoparticles also revealed the increased potential of antioxidant activity. In-vivo studies of both nanoparticles exhibited anti-diabetic properties by significantly enhancing the level of insulin. The cholesterol profiling of both nanoparticles proved the reduction of levels of serum cholesterol, triglycerides, HDL, VLDL, LDL, and creatinine content signifying the decreasing risk of macrovascular complications associated with diabetes. However, gold nanoparticles produced a more protective effect as compared to cobalt oxide nanoparticles. The study concludes that the magnetic and gold nanoparticles conjugated with Clitoria ternatea exhibited potential anti-diabetic and antioxidant activities in a streptozotocin-induced diabetic rat model.

Accelerated Wound Healing in Diabetic Rat by miRNA-185-5p and Its Anti-Inflammatory Activity.

Addressing both inflammation and epithelialization during the treatment of diabetic foot ulcers is an important step, but current treatment options are limited. MiRNA has important prospects in the treatment of diabetic foot refractory wound ulcers. Previous studies have reported that miR-185-5p reduces hepatic glycogen production and fasting blood glucose levels. We herein hypothesized that miR-185-5p might play an important role in the field of diabetic foot wounds. MiR-185-5p in skin tissue samples from patients with diabetic ulcers and diabetic rats were measured using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes rat model (male Sprague-Dawley rats) for diabetic wound healing was conducted. The therapeutic potential was observed by subcutaneous injection of miR-185-5p mimic into diabetic rat wounds. The anti-inflammation roles of miR-185-5p on human dermal fibroblast cells were analyzed. We found that miR-185-5p is significantly downregulated in diabetic skin (people with DFU and diabetic rats) compared to controls. Further, in vitro upregulation of miR-185-5p decreased the inflammatory factors (IL-6, TNF-α) and intercellular adhesion molecule 1 (ICAM-1) of human skin fibroblasts under advanced glycation end products (AGEs). Meanwhile, the increase of miR-185-5p promoted cell migration. Our results also confirmed that the topical increase of miR-185-5p decreases diabetic wound p-nuclear factor-κB (p-NF-κB), ICAM-1, IL-6, TNF-α, and CD68 expression in diabetic wounds. MiR-185-5p overexpression boosted re-epithelization and expedited wound closure of diabetic rats. MiR-185-5p accelerated wound healing of diabetic rats, reepithelization, and inhibited the inflammation of diabetic wounds in the healing process, a potentially new and valid treatment for refractory diabetic foot ulcers.

Antox Repro-protective Synergistic Role with Insulin in a Streptozotocin-Induced Diabetic Rat Model (Biochemical, Histo-morphometric and Immunohistochemical study)

Antox Repro-protective Synergistic Role with Insulin in a Streptozotocin-Induced Diabetic Rat Model (Biochemical, Histo-morphometric and Immunohistochemical study)

In vivo antidiabetic and antioxidant activities of Prosopis africana fruit extracts in streptozotocin-induced diabetic Wistar rats

In vivo antidiabetic and antioxidant activities of Prosopis africana fruit extracts in streptozotocin-induced diabetic Wistar rats

Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

BackgroundDiabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus, which is characterized by early occurrence of albuminuria and end-stage glomerulosclerosis. Senescence and autophagy of podocytes play an important role in DN development. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have potential in the treatment of diabetes and its complications. However, the role of hucMSCs in the treatment of DN and the underlying mechanism remain unclear.MethodsIn vivo, a streptozotocin-induced diabetic male Sprague Dawley rat model was established to determine the renoprotective effect of hucMSCs on DN by biochemical analysis, histopathology, and immunohistochemical staining of renal tissues. And the distribution of hucMSCs in various organs in rats within 168 h was analyzed. In vitro, CCK8 assay, wound healing assay, and β-galactosidase staining were conducted to detect the beneficial effects of hucMSCs on high glucose-induced rat podocytes. Real-time PCR and western blot assays were applied to explore the mechanism of action of hucMSCs.ResultsThe in vivo data revealed that hucMSCs were distributed into kidneys and significantly protected kidneys from diabetic damage. The in vitro data indicated that hucMSCs improved cell viability, wound healing, senescence of the high glucose-damaged rat podocytes through a paracrine action mode. Besides, the altered expressions of senescence-associated genes (p16, p53, and p21) and autophagy-associated genes (Beclin-1, p62, and LC3) were improved by hucMSCs. Mechanistically, hucMSCs protected high glucose-induced injury in rat podocytes by activating autophagy and attenuating senescence through the AMPK/mTOR pathway.ConclusionsIn conclusion, hucMSCs might be a promising therapeutic strategy for the clinical treatment of DN-induced renal damages.

Antagonistic Insulin Derivative Suppresses Insulin-Induced Hypoglycemia.

Insulin derivatives provide new functions that are distinctive from native insulin. We investigated insulin modifications on the C-terminal A chain with insulin receptor (IR) peptide binders and presented a full and potent IR antagonist. We prepared insulin precursors featuring a sortase A (SrtA) recognition sequence, LPETGG, at the C-terminal A chain and used a SrtA-mediated ligation method to synthesize insulin derivatives. The insulin precursor exhibits full IR agonism potency, similar to native human insulin. We explored derivatives with linear IR binding peptides attached to the insulin C-terminal A chain. One insulin derivative with an IR binder (Ins-AC-S2) can fully antagonize IR activation by insulin, as confirmed by cell-based assays. This IR antagonist suppresses insulin-induced hypoglycemia in a streptozotocin-induced diabetic rat model. This study provides a new direction toward insulin antagonist development.

In vivo assessment of antidiabetic activity and safety of polyherbal teas from selected Cameroonian medicinal plants: Persea americana, Ageratum conyzoides and Mangifera indica

Background: Diabetes mellitus (DM) is a metabolic disorder of the endocrine system which results in persistently high blood glucose levels. Available control measures do not completely cure the disease and most patients in the tropics cannot afford diabetes drugs regularly. Amongst other plants, Mangifera indica (MI), Persea americana (PA), and Ageratum conyzoides (AC) are used individually as traditional medicine by most people for the management of diabetes. This work was set to produce polyherbal teas (water infusion) from these plants and evaluate in vivo antidiabetic activity and safety of the teas. Methods: Three (3) monoherbal teas (MI, PA, AC) and 4 polyherbal of which 3 composed of two plants each (MI+PA, MI+AC, PA+AC) and one including all the plants (MI+PA+AC) were formulated. The antidiabetic activity was assessed by evaluating the hypoglycaemic activity of the teas by carrying out the oral glucose tolerance test (OGTT) in male Wistar albino rats and the subacute antidiabetic assay in streptozotocin-induced diabetic rats. Safety was evaluated using the in vivo acute toxicity test in mouse model. Results: The OGTT revealed a significant drop in post-prandial glucose peak in rats treated with 20mg/kg monoherbal tea from Mangifera indica leaf (MI), as compared to the negative control (distilled water). The polyherbal tea of all three plants (AC+MI+PA) at a dose of 20mg/kg was able to return the glucose levels to normal 30mins after the glucose peak. The tea AC+MI+PA also exhibited a higher antidiabetic activity as it produced a 60% glycemia recovery rate compared to the reference drug glibenclamide and monoherbal tea MI with 40% and 20% recovery rate respectively. Polyherbal tea and MI exhibited hepato-protective and nephron-protective activities. The in vivo acute toxicity test showed that the teas were not toxic as there was no record of mortality and adverse effects in physical appearance, behavior, change in body weight, water, and food intake. Conclusion: Out of the seven teas produced, two showed promising antidiabetic potential, with both acute hypoglycemic effects and significant subacute efficacy. Further investigations are envisaged to pursue the development of improved alternative therapies from these, to address the enduring challenge of diabetes, particularly in resource-limited settings. Keywords: Diabetes mellitus; antidiabetic; activity; polyherbal tea.

Linagliptin in Combination with Emblica officinalis Gaertn Improves Glycemic Control through Alleviating Dyslipidemia and Oxidative Stress on Streptozotocin Induced Diabetic Rats

Objectives: Diabetes is a complex chronic metabolic disorder. Today, many diabetes patients are known to supplement their standard therapies with herbal medications that have antidiabetic characteristics. The purpose of the study was to examine the fixed dose combination of linagliptin and Emblica officinalis Gaertn (aq FE) for its hypoglycemic, hypolipidemic, and antioxidant properties.&#x0D; Methods: Streptozotocin (45 mg/kg b.w.) was administered intraperitoneally to Wister albino rats to cause diabetes. Linagliptin (5 mg/ 70kg b.w), aqueous fruit extract of Emblica officinalis Gaertn (200 mg/kg b.w.) and fixed dose combination therapy of linagliptin (2.5 mg /70kg b.w) with aqueous fruit extract of Emblica officinalis Gaertn (100 mg/kg b.w) were administered orally once daily for four weeks. After that fasting blood glucose level (FBG), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) were measured in serum with streptozotocin (STZ)-induced diabetes. Typical procedures were used to measure the antioxidant activity by the estimation of catalase (CAT) and superoxide dismutase (SOD) activity.&#x0D; Results: The combination therapy significantly (p&lt;0.05) reduced the FBG, TC, TG, LDL level in compared to the diabetic control group (p&lt;0.05). Significant (p&lt;0.05) increased of HDL was also observed. The antioxidant activity significantly increased after the administration of fixed dose combination therapy in compared to diabetic control group. These alterations were vastly superior to those of linagliptin with Emblica officinalis Gaertn (aqFE) monotherapy.&#x0D; Conclusion: This study suggests that the fixed dose combination therapy of linagliptin and Emblica officinalis Gaertn (aq FE) might be potent on antihyperglycemic antidyslipidemic and antioxidative effect.

Lauric acid improves hormonal profiles, antioxidant properties, sperm quality and histomorphometric changes in testis and epididymis of streptozotocin-induced diabetic infertility rats

Lauric acid, a 12‑carbon atom medium chain fatty acid (MCFA) has strong antioxidant and antidiabetic activities. However, whether lauric acid can ameliorate hyperglycaemia-induced male reproductive damage remains unclear. The study aimed to determine the optimal dose of lauric acid with glucose-lowering activity, antioxidant potential and tissue-protective effects on the testis and epididymis of streptozotocin (STZ)-induced diabetic rats. Hyperglycaemia was induced in Sprague Dawley rats by an intravenous injection of STZ at a dose of 40 mg/kg body weight (bwt). Lauric acid (25, 50 and 100 mg/kg bwt) was administered orally for eight weeks. Weekly fasting blood glucose (FBG), glucose tolerance and insulin sensitivity were examined. Hormonal profiles (insulin and testosterone), lipid peroxidation (MDA) and antioxidant enzyme (SOD and CAT) activities were measured in the serum, testis and epididymis. The reproductive analyses were evaluated based on sperm quality and histomorphometry. Lauric acid administration significantly improved FBG levels, glucose tolerance, hormones-related fertility and oxidant-antioxidant balance in the serum, testis and epididymis compared to untreated diabetic rats. Treatment with lauric acid preserved the testicular and epididymal histomorphometry, along with the significant improvements in sperm characteristics. It is shown for the first time that lauric acid treatment at 50 mg/kg bwt is the optimal dose for ameliorating hyperglycaemia-induced male reproductive complications. We conclude that lauric acid reduced hyperglycaemia by restoring insulin and glucose homeostasis, which attributes to the regeneration of tissue damage and sperm quality in STZ-induced diabetic rats. These findings support the correlation between oxidative stress and hyperglycaemia-induced male reproductive dysfunctions.

Nonselective and A2a-Selective Inhibition of Adenosine Receptors Modulates Renal Perfusion and Excretion Depending on the Duration of Streptozotocin-Induced Diabetes in Rats.

Long-lasting hyperglycaemia may alter the role of adenosine-dependent receptors (P1R) in the control of kidney function. We investigated how P1R activity affects renal circulation and excretion in diabetic (DM) and normoglycaemic (NG) rats; the receptors' interactions with bioavailable NO and H2O2 were also explored. The effects of adenosine deaminase (ADA, nonselective P1R inhibitor) and P1A2a-R-selective antagonist (CSC) were examined in anaesthetised rats, both after short-lasting (2-weeks, DM-14) and established (8-weeks, DM-60) streptozotocin-induced hyperglycaemia, and in normoglycaemic age-matched animals (NG-14, NG-60, respectively). The arterial blood pressure, perfusion of the whole kidney and its regions (cortex, outer-, and inner medulla), and renal excretion were determined, along with the in situ renal tissue NO and H2O2 signals (selective electrodes). The ADA treatment helped to assess the P1R-dependent difference in intrarenal baseline vascular tone (vasodilation in DM and vasoconstriction in NG rats), with the difference being more pronounced between DM-60 and NG-60 animals. The CSC treatment showed that in DM-60 rats, A2aR-dependent vasodilator tone was modified differently in individual kidney zones. Renal excretion studies after the ADA and CSC treatments showed that the balance of the opposing effects of A2aRs and other P1Rs on tubular transport, seen in the initial phase, was lost in established hyperglycaemia. Regardless of the duration of the diabetes, we observed a tonic effect of A2aR activity on NO bioavailability. Dissimilarly, the involvement of P1R in tissue production of H2O2, observed in normoglycaemia, decreased. Our functional study provides new information on the changing interaction of adenosine in the kidney, as well as its receptors and NO and H2O2, in the course of streptozotocin diabetes.

Phthalocyanine-based glucose-responsive nanocochleates for dynamic prevention of β-cell damage in diabetes

Phthalocyanine is a blue-colored macrocyclic compound with excellent anti-oxidant and lipid-peroxidation abilities due to its intermolecular π–π stacking structure. Antioxidants inhibit intracellular reactive oxygen species formation and decrease oxidation defense ability of the enzymes in diabetes management. The present study aimed to fabricate concanavalin A conjugated phthalocyanine-loaded cochleates (Formulation PhConA) as a glucose-sensitive lipidic system and estimate its efficacy in streptozotocin-induced male Sprague Dawley diabetic rats for 28 days. Thin-film hydration and trapping methods were used in the preparation of liposomes and cochleates, respectively, whereas the surface was modified for concanavalin A conjugation using EDAC: NHS (1:1). Formulation PhConA with rod-shaped structures showed particle size of 415.7 ± 0.46 nm, PdI value of 0.435 ± 0.09, encapsulation efficiency of 85.64 ± 0.34%, and 84.55 ± 0.29% release of phthalocyanine for 56 h. The circular dichroism study displayed a slight deviation after the conjugation effect of concanavalin A to cochleates. The in-vivo studies of the formulation PhConA improved the blood glucose levels along with defensive effect on the liver to overcome the hyperlipidemic effect. The rigid structure of cochleates prolongs the drug elimination from systemic circulation and extends its effect for a longer duration by decreasing the blood glucose level. Thus, the glucose-sensitive formulation PhConA showed significant improvement in diabetic rats within the period of 28 days by improving the oxidative defense and protecting the pancreatic β-cells.

Biochemical and histopathological evaluation of ChAdOx1-S and BBIBP-CorV vaccination in normal and streptozotocin-induced diabetic Wistar rats.

Infection with Covid-19 has been associated with some medical complications namely diabetes, thrombosis, and hepatic and renal dysfunction among others. This situation has created some concern about the use of relevant vaccines which might cause similar complications. In that regard, we planned to evaluate the impact of two of the relevant vaccines namely ChAdOx1-S and BBIBP-CorV on some of the blood biochemical factors and also on liver and kidneys functions following the immunization of healthy and streptozotocin-induced diabetic rats. Evaluation of the level of neutralizing antibody among the rats indicated that immunization with ChAdOx1-S induced a higher level of neutralizing antibody among both the healthy and diabetic rats compared to the BBIBP-CorV vaccine. Furthermore, the neutralizing antibody levels against both types of vaccines were significantly lower in diabetic rats than in healthy ones. On the other hand, no alterations were observed in the rats' sera biochemical factors, coagulation values and histopathological images of the liver and kidneys. Altogether these data besides of confirming the effectiveness of both vaccines, indicate that both vaccines have no hazardous side effects on rats and probably humans though clinical investigations are required to validate our present data.

Comparative Evaluation of Antidiabetic Activity of Ethanolic Leaf Extract of Clematis Gouriana and Their SMEDDS Formulation in Streptozotocin Induced Diabetic Rats

Comparative Evaluation of Antidiabetic Activity of Ethanolic Leaf Extract of Clematis Gouriana and Their SMEDDS Formulation in Streptozotocin Induced Diabetic Rats