Streptozotocin-induced Diabetes Mellitus Research Articles

Phloretamide Prevent Hepatic and Pancreatic Damage in Diabetic Male Rats by Modulating Nrf2 and NF-κB.

This study examined the effect of phloretamide, a metabolite of phloretin, on liver damage and steatosis in streptozotocin-induced diabetes mellitus (DM) in rats. Adult male rats were divided into two groups: control (nondiabetic) and STZ-treated rats, each of which was further treated orally with the vehicle phloretamide 100 mg or 200 mg. Treatments were conducted for 12 weeks. Phloretamide, at both doses, significantly attenuated STZ-mediated pancreatic β-cell damage, reduced fasting glucose, and stimulated fasting insulin levels in STZ-treated rats. It also increased the levels of hexokinase, which coincided with a significant reduction in glucose-6 phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase 1 (PBP1) in the livers of these diabetic rats. Concomitantly, both doses of phloretamide reduced hepatic and serum levels of triglycerides (TGs) and cholesterol (CHOL), serum levels of low-density lipoprotein cholesterol (LDL-c), and hepatic ballooning. Furthermore, they reduced levels of lipid peroxidation, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), mRNA, and total and nuclear levels of NF-κB p65, but increased mRNA levels, total and nuclear levels of Nrf2, as well as levels of reduced glutathione (GSH), superoxide dismutase (SOD-1), catalase (CAT), and heme-oxygenase-1 (HO-1) in the livers of diabetic rats. All of these effects were dose-dependent. In conclusion, phloretamide is a novel drug that could ameliorate DM-associated hepatic steatosis via its powerful antioxidant and anti-inflammatory effects. Mechanisms of protection involve improving the β-cell structure and hepatic insulin action, suppressing hepatic NF-κB, and stimulating hepatic Nrf2.

Increased Renal Medullary NOX-4 in Female but Not Male Mice during the Early Phase of Type 1 Diabetes: Potential Role of ROS in Upregulation of TGF-β1 and Fibronectin in Collecting Duct Cells

Chronic diabetes mellitus (DM) can lead to kidney damage associated with increased reactive oxygen species (ROS), proteinuria, and tubular damage. Altered protein expression levels of transforming growth factor-beta 1 (TGF-β1), fibronectin, and renal NADPH oxidase (NOX-4) are associated with the profibrotic phenotype in renal tubular cells. NOX-4 is one of the primary sources of ROS in the diabetic kidney and responsible for the induction of profibrotic factors in collecting duct (CD) cells. The renal medulla is predominantly composed of CDs; in DM, these CD cells are exposed to high glucose (HG) load. Currently there is no published literature describing the expression of these markers in the renal medulla in male and female mice during the early phase of DM, or the role of NOX-4-induced ROS. Our aim was to evaluate changes in transcripts and protein abundances of TGF-β1, fibronectin, and NOX-4 along with ROS levels in renal medullary tissues from male and female mice during a short period of streptozotocin (STZ)-induced type 1 DM and the effect of HG in cultured CD cells. CF-1 mice were injected with or without a single dose of STZ (200 mg/kg) and euthanized at day 6. STZ females showed higher expression of fibronectin and TGF-β1 when compared to control mice of either gender. Interestingly, STZ female mice showed a >30-fold increase on mRNA levels and a 3-fold increase in protein levels of kidney medullary NOX-4. Both male and female STZ mice showed increased intrarenal ROS. In primary cultures of inner medullary CD cells exposed to HG over 48 h, the expression of TGF-β1, fibronectin, and NOX-4 were augmented. M-1 CD cells exposed to HG showed increased ROS, fibronectin, and TGF-β1; this effect was prevented by NOX-4 inhibition. Our data suggest that at as early as 6 days of STZ-induced DM, the expression of profibrotic markers TGF-β1 and fibronectin increases in renal medullary CD cells. Antioxidants mechanisms in male and female in renal medullary tissues seems to be differentially regulated by the actions of NOX-4.

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 effect of hyperglycemia on the activation of peritoneal macrophages of albino rats.

Hyperglycemia is one of the main damaging factors of diabetes mellitus (DM). The severity of this disease is most clearly manifested under conditions of the inflammatory process. In this work, we have studied the activation features of rat peritoneal macrophages (MPs) under conditions of high glucose concentration in vitro. Comparison of the independent and combined effects of streptozotocin-induced DM and hyperglycemia on proliferation and accumulation of nitrites in the MPs culture medium revealed similarity of their effects. Elevated glucose levels and, to a lesser extent, DM decreased basal proliferation and NO production by MPs in vitro. The use of the protein kinase C (PKC) activator, phorbol ester (PMA), abolished the proinflammatory effect of thrombin on PMs. This suggests the involvement of PKC in the effects of the protease. At the same time, the effect of thrombin on the level of nitrites in the culture medium demonstrates a pronounced dose-dependence, which was not recognized during evaluation of proliferation. Proinflammatory activation of MPs is potentiated by hyperglycemia, one of the main pathological factors of diabetes. Despite the fact that high concentrations of glucose have a significant effect on proliferation and NO production, no statistically significant differences were found between the responses of MPs obtained from healthy animals and from animals with streptozotocin-induced DM. This ratio was observed for all parameters studied in the work, during analysis of cell proliferation and measurement of nitrites in the culture medium. Thus, the results obtained indicate the leading role of elevated glucose levels in the regulation of MPs activation, which is comparable to the effect of DM and even "masks" it.

Functional state of the mesenteric arteries with higt fat intake in rats with streptozotocin-induced diabetes

An increase in the incidence of diabetes mellitus (DM) is associated with excessive consumption of fats and carbohydrates, while DM leads to the development of cardiovascular diseases. The aim of the research was to evaluate the effect of a high-fat diet (HFD) on the functional state of the mesenteric arteries in vivo in Wistar rats with DM. Material and methods. The study was conducted on 45 male Wistar rats with an initial body weight of 220-240 g, which were divided into 3 equal groups. Animals of the control group received a standard diet for 3 months. Rats of the second group (STZ) were fed a standard diet, after 8 weeks the animals were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg body weight). Animals in the STZ+HFD group received HFD (50% beef tallow), and an injection of STZ (35 mg/kg). We assessed the effect of HFD on endothelium-dependent and endothelium-free reactions of phenylephrine (PE) precontracted mesenteric arteries under the action of agonists in the absence and use of blockers of NO-synthase (L-NAME), cyclooxygenase (indomethacin), and K+-channels (tetraethylammonium), using microphoto- and videorecording of vessel diameter in vivo. Results. DM in rats led to an increase in the constrictor reaction to FE; in animals of the STZ+HFD group, the diameter of the vessel decreased by 63.7±4.7%; in the STZ group, by 60.4±3.8%; and in the control group, by 48.9±4.1%. HFD and DM induction had no effect on the amount of relaxation under the action of sodium nitroprusside. The amplitude of acetylcholine-induced relaxation of the mesenteric arteries of rats with DM in the absence of blockers was significantly lower (by 27.1% on average in the STZ+HFD group, by 14.6% in the STZ group) compared with control animals. After NO synthase inhibition, the relaxation amplitude decreased in the STZ+HFD group by 48.6±3.2%, in the STZ group by 56.1±2.8%, and in control animals by 58.3±3.1% compared with the dilatation amplitude without the use of a blocker. Acetylcholine-induced vascular dilatation under conditions of simultaneous use of a complex of three blockers - L-NAME, indomethacin and tetraethylammonium was reduced in rats with DM treated with HFD by an average of 18.9% and in animals of the STZ group by 22.1% compared with control animals. Conclusion. Thus, excessive fat intake in rats with STZ-induced DM enhances the impairment of the functional state of the mesenteric arteries compared to animals with DM that received a standard diet. In HFD in rats with DM, a decrease in endotheliumdependent vasodilation was mediated as a failure of NO-dependent relaxation mechanisms and a decrease in the efficiency of the mechanism of endothelial hyperpolarization, whereas in rats with DM fed a standard diet, it was predominantly a disturbance in the mechanism of endothelial hyperpolarization.

LC-MS-based metabolite profiling of aqueous extract of Pergularia tomentosa L. and its anti-hyperglycemic effect.

In this study, to find scientific evidence for the traditional use of Pergularia tomentosa as an anti-diabetic remedy, the effects of its aqueous extract on streptozotocin-induced diabetes mellitus in rats were evaluated. Wistar rats were fasted overnight and diabetes mellitus was induced using streptozotocin (50 mg/kg body weight). The rats were randomly and equally divided into four groups (n=5): group I (normoglycaemic control), group II (diabetic rats), group III (diabetic rats treated with 200 mg/kg BW of an aqueous extract of P. tomentosa), group IV (normoglycemic rats treated with 200 mg/kg BW of an aqueous extract of P. tomentosa). Chemical profiling of the aqueous extract was carried out using liquid chromatography coupled with electrospray ionization and multiple-stage linear ion-trap and orbitrap high-resolution mass spectrometry (LC-ESI/LTQOrbitrap/MS/MS). In addition, the quantitative determination of the main cardenolides in the extract was carried out by an analytical approach based on LC coupled to tandem mass spectrometry with ESI source and hybrid triple quadrupole-linear ion trap mass analyzer (LC-ESI/QTrap/MS/MS). Aqueous extract of P. tomentosa showed a reasonable reduction in blood glucose level. Probably, the P. tomentosa effect on hyperglycemic and hyperlipidemic diabetic animals was associated with antioxidant properties, triglyceride levels, as well as liver enzymes. Meanwhile, LC-ESI/LTQOrbitrap/MS/MS analysis led to identification of double-linked cardenolides along with cardenolides and flavone glycosides as the main bioactive compounds. The extract decreased the glucose level and induced a beneficial effect on the lipid profile, probably due to the presence of cardenolide glycosides.

Zinc Chloride Enhances the Antioxidant Status, Improving the Functional and Structural Organic Disturbances in Streptozotocin-Induced Diabetes in Rats.

Background and Objectives: Diabetes mellitus (DM) is a complex disease affecting the whole metabolic balance of the body and resulting in multiple organ complications: cardiovascular, neuronal, renal, etc. Our study focuses on investigating the effect of zinc chloride (Zn) on certain blood parameters suggestive for assessing the metabolic disturbances, the liver and kidney function, the oxidative stress and the immune defense capacity in experimental-induced DM with streptozotocin (STZ) and cholesterol in rats. Materials and Methods: The animals were assigned to three groups, as follows: Group 1 (Control): buffer citrate solution 0.1 mL/100 g body; Group 2 (STZ): 20 mg/kg body STZ and fat diet (10 g cholesterol/100 g diet); Group 3 (STZ+Zn): 20 mg/kg body STZ + 5 mg/kg body Zn chloride and the same fat diet. DM was induced by administering STZ in a single take daily, for three consecutive days, Zn and citrate buffer were administered orally for a month. The protocol was approved by the Ethics Committee of the University 'Grigore T Popa' Iasi, in agreement with the International Regulations about the handling of laboratory animals. Results: The use of STZ in rats fed with cholesterol was correlated with important weight gain, hyperglycemia, the intensification of the transaminases activity and the increase in serum alkaline phosphatase, cholesterol, triglyceride, urea, creatinine and in malondialdehyde. Conclusions: The treatment with Zn resulted in weight loss and a decrease in blood sugar in diabetic rats. Supplementation with Zn notably reduced oxidative stress, preserved the pancreatic architecture and restored the liver and kidney function and structure in STZ-induced DM in rats.

Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein-mediated viral translation.

Diabetes mellitus (DM) is highly comorbid with severe dengue diseases; however, the underlying mechanisms are unclear. Patients with DM have a 1.61-fold increased risk of developing dengue hemorrhagic fever. In search of host factors involved in dengue virus (DENV) infection, we used high-glucose (HG) treatment and showed that HG increased viral protein expression and virion release but had no effects on the early stages of viral infection. After HG stimulation, DENV-firefly luciferase-transfected assay and cellular replicon-based assay indicated increased viral translation, whereas using the glucose uptake inhibitor phloretin blocked this effect. HG treatment increased the translational factor poly(A)-binding protein (PABP) in a glucose transporter-associated, PI3K/AKT-regulated manner. Silencing PABP significantly decreased HG-prompted virion production. HG enhanced the formation of the PABP-eukaryotic translation initiation factor 4G complex, which is regulated by protein-disulfide isomerase. Hyperglycemia increased PABP expression, mortality rate, viral protein expression, and viral loads in streptozotocin-induced DM mice. Overall, hyperglycemic stress facilitates DENV infection by strengthening PABP-mediated viral translation.

Hyperglycemia with or without insulin resistance triggers different structural changes in brain microcirculation and perivascular matrix.

Both type-1 and type-2 DM are related to an increased risk of cognitive impairment, neurovascular complications, and dementia. The primary triggers for complications are hyperglycemia and concomitant insulin resistance in type-2 DM. However, the diverse mechanisms in the pathogenesis of diabetes-related neurovascular complications and extracellular matrix (ECM) remodeling in type-1 and 2 have not been elucidated yet. Here, we investigated the high fat-high sucrose (HFHS) feeding model and streptozotocin-induced type-1 DM model to study the early effects of hyperglycemia with or without insulin resistance to demonstrate the brain microcirculatory changes, perivascular ECM alterations in histological sections and 3D-reconstructed cleared brain tissues. One of the main findings of this study was robust rarefaction in brain microvessels in both models. Interestingly, the HFHS model leads to widespread non-functional angiogenesis, but the type-1 DM model predominantly in the rostral brain. Rarefaction was accompanied by basement membrane thickening and perivascular collagen accumulation in type-1 DM; more severe blood-brain barrier leakage, and disruption of perivascular ECM organization, mainly of elastin and collagen fibers' structural integrity in the HFHS model. Our results point out that the downstream mechanisms of the long-term vascular complications of hyperglycemia models are structurally distinctive and may have implications for appropriate treatment options.

Photobiomodulation therapy protects red blood cells against nitrative stress during streptozotocin-induced diabetes

Background. According to the International Diabetes Federation Diabetes Atlas, 10th edition, diabetes is responsible for 6.7 million deaths in 2021. Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia secondary to either resistance to insulin, insufficient insulin secretion, or both. Oxidative and nitrative stress is a vital part of the complex mechanism by which diabetes and its complications develop. It is known that Photobiomodulation therapy accelerates diabetic wound healing, treats relegated inflammation, and increases oxygen availability for cells. Although some basic molecular mechanisms caused by photobiomodulation therapy in different cell types are already known, they have not been studied in erythrocytes and are different due to the absence of central organelles such as nucleus and mitochondria. The aim of the study was to investigate the effect of photobiomodulation therapy on the development of nitrative stress in blood plasma and erythrocytes of rats from different experimental groups. Materials and Methods. The study was performed on white outbred male rats weighing 130–180 g. The diabetes mellitus was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Rats were exposed to photobiomodulation with light-emitting diodes at a wavelength of 630–660 nm daily for 10 days. The irradiation time was 5 minu­tes. The content of nitrite and nitrate anions, total NO synthase activity, as well as the activity of its endothelial and inducible isoforms in red blood cells of rats were determined spectrophotometrically. Results and Discussion. Under streptozotocin-induced diabetes mellitus, the content of nitrite and nitrate anions and NO synthase activity increased in the rats’ red blood cells, as well as in blood plasma. Moreover, we found an increase in inducible NO synthase activity and nitrate ion content in red blood cells of irradiated healthy rats. Also, there was an increase in nitrite and nitrate ion content after photobiomodulation therapy in the blood plasma of healthy animals. On the other hand, irradiation caused a decrease in NO synthase activity with a parallel reduction in both nitrite and nitrate anions content in erythrocytes and blood plasma of rats with experimental diabetes. Conclusion. Photobiomodulation therapy protects rats’ red blood cells from nitrative stress during streptozotocin-induced diabetes mellitus.

Dynamics of endogenous intoxication in experimental diabetes mellitus

Background. Nowadays, diabetes mellitus is defined as one of the global medical and social problems and shows a growing tendency. The purpose of the study was to analyze the dynamics of endogenous intoxication in experimental diabetes mellitus. Materials and methods. The experiments were performed on 88 white male Wistar rats weighing 170-210 g. Animals were divided into three groups: 1 - intact; 2 - control; 3 - experimental with a model of diabetes mellitus, which was reproduced by intraperitoneal injection of streptozotocin by “Sigma" company (USA), diluted in 0.1 M citrate buffer with a pH of 4.5, at a rate of 60 mg/kg body weight. The control group of animals received an intraperitoneal injection with an equivalent dose of 0.1 M citrate buffer solution with a pH of 4.5.
 All studies were performed under thiopental-sodium anesthesia at a rate of 60 mg/kg body weight. To determine endogenous intoxication, blood sampling of middle mass molecules (MMM) was performed 14, 28, 42 and 70 days after the streptozotocin injection. Detection of MMM fractions was performed by spectrophotometer «SF46» at the wavelength of 254 nm (MMM254) and 280 nm (MMM280). The STATISTICA 10 program was used for statistical processing of the obtained results. Results. The conducted biochemical studies of blood serum showed that in animals with streptozotocin-induced diabetes mellitus there was an increase in the content of both MMM fractions compared to the similar indicators of the control group of animals at all stages of the experiment: in the 14 days increased by 32,9% - MMM254, by 12.7%- MMM280, in the 28 days increased by 44,3 % MMM254, by 34,0 % MMM 280, in the 42 days increased by 62,8 % MMM254, by 64,8 % MMM280, in 70 days increased by 76,1 % MMM254, by 81,1% MMM280. Conclusions. Streptozotocin-induced diabetes mellitus is accompanied by an increase in the level of endogenous intoxication which is manifested by an increase of both MMM fractions content in serum.
 The severity of endogenous intoxication depends on the duration of the endogenous factor.

Ketogenic diet modulates cardiac metabolic dysregulation in streptozocin-induced diabetic rats

The ketogenic diet (KD) might improve cardiac function in diabetic cardiomyopathy, but the mechanisms remain unclear. This study investigated the effects of KD on myocardial fatty acid (FA), glucose, and ketone metabolism in diabetic cardiomyopathy. Echocardiograms, biochemistry, and micro-positron emission tomography were performed to evaluate cardiac function and glucose uptake in control rats and streptozotocin-induced diabetes mellitus (DM) rats with normal diet (ND) or KD for 6 weeks. Histopathology, adenosine triphosphate measurement, and Western blot were performed in the ventricular myocytes to analyze fibrosis, FA, ketone body, and glucose utilization. The ND-fed DM rats exhibited impaired left ventricular systolic function and increased chamber dilatation, whereas control and KD-fed DM rats did not. The KD reduced myocardial fibrosis and apoptosis in the DM rats. Myocardial glucose uptake in the micro-positron emission tomography was similar between ND-fed DM rats and KD-fed DM rats and was substantially lower than the control rats. Compared with the control rats, ND-fed DM rats had increased phosphorylation of acetyl CoA carboxylase and higher expressions of CD-36, carnitine palmitoyltransferase-1β, tumor necrosis factor-α, interleukin-1β, interleukin6, PERK, and e-IF2α as well as more myocardial fibrosis and apoptosis (assessed by Bcl-2, BAX, and caspase-3 expression); these increases were attenuated in the KD-fed DM rats. Moreover, ND-fed DM rats had significantly lower myocardial adenosine triphosphate, BHB, and OXCT1 levels than the control and KD-fed DM rats. The KD may improve the condition of diabetic cardiomyopathy by suppressing FA metabolism, increasing ketone utilization, and decreasing endoplasmic reticulum stress and inflammation.

Dichloroacetate as a metabolic modulator of heart mitochondrial proteome under conditions of reduced oxygen utilization

Myocardial compensatory mechanisms stimulated by reduced oxygen utilization caused by streptozotocin-induced diabetes mellitus (DM) and treated with dichloroacetate (DCA) are presumably associated with the regulation of mitochondria. We aimed to promote the understanding of key signaling pathways and identify effectors involved in signal transduction. Proteomic analysis and fluorescence spectroscopy measurements revealed significantly decreased membrane potential and upregulated protein amine oxidase [flavin-containing] A (AOFA) in DM mitochondria, indicative of oxidative damage. DCA in diabetic animals (DM + DCA) downregulated AOFA, increased membrane potential, and stimulated thioredoxin-dependent peroxide reductase, a protein with antioxidant function. Furthermore, the DM condition was associated with mitochondrial resistance to calcium overload through mitochondrial permeability transition pores (mPTPs) regulation, despite an increased protein level of voltage-dependent anion-selective protein (VDAC1). In contrast, DM + DCA influenced ROS levels and downregulated VDAC1 and VDAC3 when compared to DM alone. The diabetic myocardium showed an identical pattern of mPTP protein interactions as in the control group, but the interactions were attenuated. Characterization of the combined effect of DM + DCA is a novel finding showing that DCA acted as an effector of VDAC protein interactions, calcium uptake regulation, and ROS production. Overall, DM and DCA did not exhibit an additive effect, but an individual cardioprotective pathway.

L-Lysine Ameliorates Diabetic Nephropathy in Rats with Streptozotocin-Induced Diabetes Mellitus.

Introduction Diabetic nephropathy is one of the leading causes of end-stage renal disease worldwide. Uncontrolled hyperglycemia and subsequent production of glycation end-products activate the paths which lead to diabetic nephropathy. The aim of this study was to assess the effects of L-lysine on antioxidant capacity, biochemical factors, kidney function, HSP70 level, and the expression of the TGFβ, VEGF, and RAGE genes in rats with streptozocin-induced diabetes mellitus. Methods Thirty-two male Wistar rats were randomly allocated to four eight-rat groups, namely, a healthy group, a diabetic group treated with vehicle (DM + vehicle), a diabetic group treated with L-lysine (DM + Lys), and a healthy group treated with L-lysine (healthy + Lys). Rats in the DM + Lys and the healthy + Lys groups were treated with L-lysine 0.15%. The levels of fasting blood glucose, insulin, HbA1C, advanced glycation end-products (AGEs), lipid profile, serum creatinine, blood urea nitrogen, glomerular filtration rate, urine microalbumin, oxidative stress parameters, kidney histology and morphology, and TGFβ, VEGF, and RAGE gene expressions were assessed. Findings. An eight-week treatment with L-lysine significantly reduced the levels of fasting blood glucose, AGEs, kidney function parameters, oxidative stress parameters, lipid profile, and the TGFβ, VEGF, and RAGE gene expression and significantly increased the levels of serum insulin and tissue HSP70. Conclusion Treatment with L-lysine seems to slow down the progression of diabetic nephropathy.

Therapeutic effects of silodosin and urapidil on underactive bladder associated with diabetic cystopathy.

Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha1 -adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha1 -AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha1A -AR antagonist) and urapidil (nonselective alpha1 -AR antagonist) on the voiding function in female rats with diabetes mellitus (DM). Changes in intraurethral pressure (IUP) induced by midodrine (alpha1 -AR agonist) and mean blood pressure (MBP) were continuously measured in normal female rats to verify the pharmacological profiles of the drugs. To establish a DM model, rats were administered streptozotocin (STZ; 50 mg/kg, intravenous). Eight weeks after STZ administration, drugs were subcutaneously delivered through an osmotic pump. Four weeks after drug administration, emptied bladder blood flow (BBF), intravesical pressure, and the micturition volume were measured. Both silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction. Alpha1 -AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha1A -AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB.

Thymus serpyllum Exhibits Anti-Diabetic Potential in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice: A Combined Biochemical and In Vivo Study.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that is characterized by hyperglycemia, insulin resistance, and lack of insulin production. It has been previously reported that Thymus serpyllum has therapeutic potential against many diseases. To investigate the antidiabetic action of Thymus serpyllum, this study aimed to analyze its restorative impact in diabetic mice, in which it was administered in diet. Diabetes was induced in BALB/c mice fed with a high-fat diet and two intraperitoneal injections of streptozotocin. With the onset of diabetes, the mice were administered daily with aqueous extract of Thymus serpyllum (500 mg/kg/d and 800 mg/kg/d) for 4 weeks. Body weight and fasting blood glucose levels were measured after every 1 week of the treatment. Subsequently, intraperitoneal glucose tolerance and insulin tolerance tests were conducted. In addition, liver tissue was isolated for assessment in terms of levels of gene expression of the AMPK, IRS1, and GLUT2 gene. Treatment with the aqueous extract of Thymus serpyllum was found to be significantly effective in controlling hyperglycemia and improving glucose and insulin tolerance. Predictable with these impacts, the extract of Thymus serpyllum upregulated the AMPK expression at the mRNA level, as well as upregulating the expression of IRS1 and GLUT2 gene. Histopathological examination of the liver, kidney, and pancreas also revealed the restorative impact in terms of cellular morphology. The results hence demonstrated that oral administration of aqueous extract of Thymus serpyllum can potentially attenuate hyperglycemia in the liver muscle of streptozotocin (STZ)-induced diabetic mice via AMPK and IRS1 upregulation.

Accelerated Wound Healing Potential of Nisin in Streptozotocin Induced Diabetes Mellitus in Wistar Rats

Accelerated Wound Healing Potential of Nisin in Streptozotocin Induced Diabetes Mellitus in Wistar Rats

Особливості системних патобіохімічних реакцій на ішемію-реперфузію головного мозку у щурів із цукровим діабетом

The objective of the research was to study the signs of oxidative stress, the state of proteolysis, and the proteinase-inhibiting system of the blood plasma in rats with streptozotocin-induced diabetes mellitus (60 mg/kg intra-abdominally), complicated by cerebral ischemia-reperfusion. Levels of products of lipid peroxide oxidation, protein oxidative modification, nitrogen oxide metabolites, and activity of the antioxidant protection enzymes were determined by means of biochemical methods one hour after completion of the reperfusion period and on the 12th day. Increased intensity of lipid peroxidation was found to occur in the blood plasma of rats without diabetes mellitus in both terms of observation. This was accompanied by an increase in the activity of all the antioxidant enzymes, while in animals with diabetes the amount of lipid peroxidation products decreased in the ground of prevailing depression of all the antioxidant protection enzymes. Irrespective of a tendency of changes in the amount of POM products with cerebral ischemia-reperfusion, their content is reliably higher in animals with diabetes mellitus in both terms of observation than those in animals without diabetes, which is indicative of a higher intensity of their oxidation. Without diabetes, the proteolytic activity of the blood plasma reacts by increasing the values of the studied parameters against the background of suppression of the proteinase inhibitory system during the entire observation period, in rats, with diabetes the parameters of plasma proteolysis and the state of the proteinase-inhibiting system remain without changes in both terms of the observation. The data obtained allowed us to state that diabetes mellitus considerably modifies the response of the systemic pathobiochemical indices to cerebral ischemia-reperfusion.

Curative and protective potentials of Moringa oleifera leaf decoction on the streptozotocin-induced diabetes mellitus in albino rats

The present study was designed to investigate the protective, and curative potentials of Moringa oleifera (MO) leaves powder against streptozotocin (STZ) induced type 1 diabetes mellitus (T1DM) in rats. Fifty adult Wistar male albino rats were randomized and divided into five equal groups: The normal control group, the Moringa group, The diabetic group, the therapeutic group, and the diabetic rats (3 days after STZ injection) were received-MO-for successive 8 weeks and the prophylactic group, the rats were received-MO-for 2 weeks before STZ induced diabetic rats and lasted for 8 weeks. The protective or treated oral administration of 1 ml freshly prepared aqueous leaf decoction of-MO-revealed a significant upregulation of the mRNA expression of PDX-1, Ngn3, VEGF, IGF-1, and GLUT-2. Additionally, it induced a significant downregulation of FBG level compared to that of the diabetic group, a significant reduction in MDA level and a significant elevation in the TAC level. Furthermore, the histopathological observations of pancreas, liver, and kidney tissues affirmed the improvement in treated and prophylactic groups compared to STZ-diabetic groups, and the improvement in the prophylactic group was more distinct than the treated group. MO-aqueous leaf extract can treat and protect against STZ-induced T1DM; via its antioxidant action (increase the TAC and decrease MDA). Thus, it has the potential for utilization as a prophylactic against diabetes.

The Role of an Aqueous Extract of Cactus on Histopancreatic Architecture in Streptozotocin Induced Diabetes Mellitus in Wistar Rats

Herbs have been used as medicinal for several years to cure or rather manage different ailments such as diabetes mellitus. This is very common in rural settings of sub-saharan Africa and is now being adopted in urban areas. Opunta species have widely been seen to contain antihyperglycaemic effects. To evaluate the antihyperglycaemic and histopancreatic effect of aqueous extract of prickly pear cactus (Opuntia species) cladodes in streptozotocin-induced diabetic male Wistar rats in vivo. This was a laboratory based research conducted at Mulungushi University involving 30 wistar rats (Rattus norvegicus) that weighed between 160-200 g which were randomly selected into five groups (6 per cage); normal control, diabetic control, diabetic +metformin, diabetic +cactus and cactus only group. Initial blood glucose levels were obtained from the tail and record then Diabetes mellitus was induced using a single intraperitoneal dose of streptozotocin (70mg/kg BW) and established a persistent state of hyperglycemia after 72hours. The aqueous cactus extract of 100 mg/kg BW and metformin of 100 mg/kg BW was administered orally using intragastric cannula daily for a period of 4 weeks. At the end of the fourth week, Diabetes + cactus and diabetes + metformin groups body weights were statistically significant when compared to the diabetic group (P<0.05). While diabetic group was statistically significant when compared to normal control (P<0.05). The relative weight of the pancreas in diabetic group was statistically significant to other groups (P<0.05). The blood glucose in diabetic + cactus was normoglycaemic at 3rd week, Diabetic + metformin group when compared to diabetic group was statistically significant (P<0.05). The normal control and cactus only groups maintained normoglycaemic till the end of the 4th week. The histological findings of the normal control and cactus only group showed normal pancreatic cytoarchitecture. Diabetes group showed high degree of disorganization in the cytoarchitecture in the islet with reduction in β cell mass and deposition of elastic fibres. The Diabetic+Metformin group showed slight decrease in the cell mass (β cells) and elastic fibres were extensively deposited. Diabetic+Cactus treated group exhibited normal histology of the pancreas with increased number of β cells. Opuntia species are able to lower elevated blood glucose levels and ameliorate the effects of STZ on the pancreatic morphology