Experimental Diabetic Rats Research Articles

The Effect of Low-Intensity Extracorporeal Shockwave Treatment on the Urinary Bladder in an Experimental Diabetic Rat Model.

PurposePreclinical data increasingly support an impact of low-intensity extracorporeal shockwave therapy (Li-ESWT) on the bladder. We investigated the molecular effects of Li-ESWT on the bladder of a streptozotocin-induced diabetic rat model.MethodsFifteen 8-week-old male Wistar rats were randomized into 3 groups: a control group (n=5), a group of diabetic rats without treatment (diabetes mellitus [DM], n=5) and a group of diabetic rats treated with Li-ESWT (DM-ESWT, n=5). A single intraperitoneal dose of streptozotocin (60 mg/kg) was used to induce diabetes. Twenty days after diabetes induction, each rat in the DM-ESWT group received 300 shockwaves with an energy flux density of 0.09 mJ/mm2. Sessions were repeated 3 times/week for 2 weeks, followed by a 2-week washout period. Total RNA from bladder tissue was extracted, cDNA was synthesized, and quantitative real-time polymerase chain reaction was performed to analyze the expression pattern of transient receptor potential vanilloid 1 (Trpv1), interleukin-1β (Il1b), and the muscarinic receptors M1, M2, and M3 (Chrm1, Chrm2, and Chrm3).ResultsThe expression of Trpv1, Il1b, and Chrm2 genes was significantly different between the 3 groups (P=0.002, P<0.0001, and P=0.011, respectively; 1-way analysis of variance). In the DM group, the expression of all genes was higher than in the control group, but statistical significance was observed only for Trpv1 and Il1b (P=0.002 and P<0.0001, respectively). Li-ESWT significantly reduced the expression of Il1b and Chrm2 (P=0.001 and P=0.011, respectively), whereas a nonsignificant tendency for reduced expression was noted for Trpv1 (P=0.069).ConclusionsThe induction of diabetes was associated with increased expression of genes related to mechanosensation, inflammation/ischemia, and contraction in the rat bladder. Li-ESWT reduced the expression of IL1b, Chrm2, and to a lesser extent Trpv1 toward the control levels, suggesting the therapeutic potential of this treatment modality for diabetic cystopathy.

Egyptian Olea europaea leaves bioactive extract: Antibacterial and wound healing activity in normal and diabetic rats

Background and aimIn vitro activity evaluation of Egyptian Olea europaea leaves extracts, and in vivo healing activity assessment of the newly prepared ointment of Olea europaea leaves extracts mingled with Shea butter. Experimental procedureDifferent extraction methods and solvents were used to extract Egyptian Olea europaea bioactive agent(s). Antibacterial, scavenging activity and in-vivo evaluation of wound repair potentiality of Olea europaea extract were examined in normal and diabetic experimental rat models with induced circular excisions. Results and conclusionOlive leaves extract of Tanta was selected as the most active agent against Methicillin-resistant S. aureus (MRSA), with MIC value 15.6 μg/ml. Moreover, checkerboard dilution technique approved that the interaction between Tanta LEM crude extract and Ciprofloxacin was synergistic. Scavenging activity of the extract against DPPH free radicals was 87.55% at concentration of 50 μg/ml. In vivo normal and diabetic experimental rats treated with Shea butter: Tanta LEM extract (1:3 w/v) showed the maximum wound contraction and healing activity.

Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats

Diabetes mellitus is mostly interrelated to deficiency in wound healing. Low-level laser therapy has been shown to exert reliable effects on the acceleration of wound healing process. This study aimed to determine the potential influence of low-level laser therapy (LLLT) on the healing of extraction sockets in diabetic rats. A total of 24 healthy male Wistar rats were selected for this study. After diabetes induction, the maxillary first molars of all rats were extracted bilaterally. Then, the animals were subjected either to Ga-Al-As laser at 808 nm or to Al-Ga-In-P laser at 660 nm at the right extracted socket every day for the next 14 days. The left sockets served as controls. Rats were sacrificed on the 3rd, 5th, 7th, and 14th days after tooth extraction. The samples were examined by a pathologist. LLLT at 808 nm was able to significantly repress inflammation, improve osteoid formation, and promote vascularization in comparison to the non-treated sockets. LLLT at 660 nm significantly suppressed inflammation and developed vascularization in comparison to the non-treated sockets, but failed to improve osteoid formation in the treated sockets. This study suggests that LLLT could be considered asa reliable treatment for wound healing in diabetic experimental rats.

Beneficial Effect of Thymelaea hirsuta on Pancreatic Islet Degeneration, Renal Fibrosis, and Liver Damages as Demonstrated in Streptozotocin-Induced Diabetic Rat.

Objective In Morocco, Thymelaea hirsuta (T. hirsuta) (Thymelaeacea) is a medicinal plant widely used to treat and prevent diabetes. The present study aimed to evaluate the medium-term antidiabetic effect of aqueous extract (AqTh) and ethyl acetate fraction (EaTh) of Th and to investigate their putative protective effect on pancreatic islet degeneration, diabetic nephropathy, and liver damages in streptozotocin (STZ)-diabetic rats. Methods Experimental diabetes in rats was induced by a single intraperitoneal injection of 50 mg/kg of STZ. During the treatment period (4 weeks), 200 mg/kg AqTh and 50 mg/kg EaTh were orally administrated daily to STZ-diabetic rats. A group of parameters including fasting blood glucose, biochemical parameters, and intestinal α-glucosidase inhibition were studied. Furthermore, histological study of the pancreas, kidney, liver, and aorta was also realized. Results At the end of the treatment, both AqTh and EaTh had normalized fasting blood glucose to 1.08 and 1.25 g/l, respectively. AqTh has also reduced urinary creatinine and HbAc1. The EaTh showed inhibitory activity against intestinal α-glucosidase, whereas AqTh did not have this inhibitory effect. Furthermore, pancreas hematoxylin and eosin staining showed that AqTh or EaTh prevents pancreatic islet cell degeneration. As the same kidney, Masson's trichrome staining has shown a significant prevention of renal fibrosis in AqTh- or EaTh-treated diabetic rats. On the other hand, liver hematoxylin and eosin staining showed that AqTh and EaTh prevent liver damage. Conclusion We conclude that medium-term administration of AqTh and EaTh exerts significant antihyperglycemic effect in STZ-diabetic rats possibly through intestinal α-glucosidase inhibition and protection against pancreatic islet cell damage. Moreover, AqTh and EaTh treatment prevent nephropathy and liver complications in STZ-diabetic rats.

Protective effect of pomegranate peel extract on diabetic ocular structural changes in experimental diabetic rats: A histological, immunohistochemical and clinical study

Ocular complications of diabetes mellitus are rapidly progressing and have become a leading cause of vision impairment. The present study evaluated the potential protective role of pomegranate peel extract, as a powerful antioxidant agent, on the ocular complications of diabetes. One hundred, 8 weeks old, male Wistar rats were subdivided into three groups; the first control group (non-diabetic) was injected intraperitoneally with a single dose (2 ml/animal) of citrate buffer alone. The second group (diabetic untreated) was subjected to induction of diabetes by an intraperitoneal single dose of streptozotocin (60 mg/kg body weight). The third group (diabetic treated) was subjected to induction of diabetes as the second group and given simultaneously, 500 mg/kg body weight of pomegranate peel extract orally once per day with the drinking water. Clinical examination of lens and fundus was made, and the biochemical analysis was done at 8, 12, 16, 20, 24, 28, 32, 36 and 40 weeks after diabetes induction. At the end of the investigation (40 weeks), the rats were anesthetized, and the eyeballs were removed and sampled for histopathological, immunohistochemical, and ultrastructural investigations. The study revealed that the lens of 12 rats from a total of 40 rats of the second group (diabetic untreated) depicted the onset of cataract at 16 week, which increased gradually. The retina of the same group showed gradual inter-retinal microvascular abnormalities and histopathological changes. The third group (diabetic treated) showed marked amelioration as compared to the second group. ANOVA test for the biomedical indicators showed a statistically significant improvement in the third group. In conclusion, the pomegranate peel extract possesses strong potential for its development as a protective agent against ocular complications of diabetes. Keywords: Pomegranate peel extract, diabetes mellitus, ocular structure, rats.

Effects of citral on serum inflammatory factors and liver gene expression of IL-6 and TNF-alpha in experimental diabetes

Citral is the main ingredient of the lemongrass plant with anti-inflammatory properties. In this study, the effects of citral on reducing inflammation in experimental diabetes in rats were investigated. Forty rats were randomly divided into four groups. There were two control groups (healthy controls (H) and citral alone-treated control (HC)) and two diabetic groups (diabetes (D) and diabetes+citral treatment (DC)). After diabetes confirmation on day 7, treatment with citral (300 mg/kg) was started for 2 weeks by gavage in the DC and HC groups. On days 0, 7, and 21 of the study, inflammatory elements of blood serum, IL-6, TNF-α, haptoglobin, and α2-macroglobulin were compared between the four groups. Also, on day 21 of the study, the expression level of IL-6 and TNF-α in the liver tissue was analyzed by quantitative real-time PCR. On day 21 of the study, following treatment with citral for 14 days, there was a significant difference in the DC group’s inflammatory factors compared to the D group (P < 0.005). However, no significant difference was observed in DC and the two control groups’ inflammatory factors. Regarding gene expression, the levels of IL-6 and TNF-α in the liver were significantly downregulated in the DC group compared to those in the D group (P < 0.05). According to the results of this study, citral can be used as a suitable ingredient to reduce the inflammatory complications of diabetes.

Effect of honey and insulin treatment on oxidative stress and nerve conduction in an experimental model of diabetic neuropathy Wistar rats.

Diabetic neuropathy is the most common complication affecting more than 50% of patients with longstanding diabetes. Till date, there are no reports to explain the scientific basis of alternative medicine as an adjunct therapy for treating diabetic neuropathy. Hence, we studied the effect of honey and insulin treatment on hyperglycemia, dyslipidemia, oxidant and anti-oxidant status and nerve conduction in experimental diabetic neuropathy Wistar rats. In this experimental study, forty healthy male Wistar albino rats of 10-12 weeks age, weighing between 150 to 200g were obtained from our institute central animal house. After acclimatization, the rats were divided into control (n = 8) and experimental (n = 32) groups randomly. In the experimental group, type 2 diabetic neuropathy was induced with high fat and high sugar diet for 8 weeks followed by streptozotocin at a dose of 35 mg/kg body weight. Three days after streptozotocin injection, blood glucose levels of rats were measured from fasting samples to confirm diabetes. After the development of diabetes, rats were given standard rodent chow and allowed four more weeks to remain diabetic and to develop neuropathy. Every second week, nerve conduction study was done to confirm neuropathy. All the diabetic rats of experimental group developed neuropathy after 4 weeks of developing diabetes, which was confirmed by significant reduction in conduction velocity of sensory and motor nerve when compared to non-diabetic control group. After the development of neuropathy, these rats were randomly divided into diabetic neuropathy with no treatment group (n = 8) and three treatment groups (n = 8, each). The rats of treatment group were administered with either honey or insulin or honey+insulin for six weeks. After six-weeks of intervention, there was significant decrease in blood glucose and lipids in honey, insulin and honey+insulin treated neuropathy rats, when compared with no treatment group. Malondialdehyde was reduced and total anti-oxidant status improved in all the three treatment groups. There was no significant increase in conduction velocity of sciatic tibial motor nerve in treatment groups when compared with no treatment group. However, the sensory nerve conduction velocity improved significantly in honey+insulin treated neuropathy rats. In conclusion, six-week honey treatment helped in reducing dyslipidemia and oxidative stress. Honey given along with insulin for six-weeks improved sensory nerve conduction velocity in experimental diabetic neuropathy Wistar rats.

Combination effect of Spirulina fusiformis with rutin or chlorogenic acid in lipopolysaccharide-induced septic cardiac inflammation in experimental diabetic rat model

Background: The connection between inflammation and hyperglycemia leads to diabetes mellitus and its complications. Nutraceuticals are natural sources which can be used as supplement food for the prevention of many disorders. Our aim was studied to the protective role of two antioxidants (Rutin and Chlorogenic acid) with Spirulina fusiformis (SP) on streptozotocin-induced diabetic rats and being challenged with lipopolysaccharide to accelerate the diabetic inflammation. Materials and Methods: Rats were distributed into eleven groups. Each group has 6 rats. Lipopolysaccharide was administered to induced inflammation in diabetes mellitus rats. Orally administered Spirulina fusiformis (500 and 1000 mg/kg), rutin and chlorogenic acid (30 and 60 mg/kg) individually or in combination for 28 days. Metformin (200 mg/kg) was used as a standard drug. Biochemical parameters, body weight, and blood pressure levels were measured at different intervals. Histological studies, Scanning Electronic Microscopy, and gene expression analysis Real-time polymerase chain reaction of NRF2 and inducible nitric oxide synthase gene were analyzed at the end of the experiment. Results: Decreased in blood glucose levels and lipid profile at different intervals were noted with combination drug therapy (Spirulina fusiformis with rutin and Spirulina fusiformis with Chlorogenic acid). Improvement in antioxidant enzymes and pro-inflammatory cytokines levels were decreased on the 45th day. Maximum diastolic blood pressure levels were decreased statistically on the 45th day. Proof of evidence was also supported with these results. Conclusion: Combination therapy was showed excellent results than individual therapy at all parameters.

Study of the beneficial effect of vanadium sulfate on the liver of experimental diabetic rats

Background and Aims: Liver is a tissue that is negatively affected by diabetes mellitus (DM). This is due to its central function in the regulation of carbohydrate metabolism. Vanadium salts, which have insulinomimetic effects, have been found to stimulate glycogenesis and glycolysis, as well as to inhibit glycogenolysis and lipolysis. The aim of this study is to evaluate the effect of vanadium sulfate (VS) on biochemical changes in liver tissue of diabetic rats. Methods: Randomly selected 6.0 - 6.5 months Swiss Albino rats were separated into two diabetic and two control groups. Group I: non treated animals. Group II: non treated animals orally administered VS (100mg/kg/day for 60 days), group III: STZinduced diabetic animals (65 mg/kg with intraperitoneally) and group IV: STZ-induced diabetic animals administered VS (at same dose and time). Antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, as well as alkaline phosphatase, glucose-6-phosphate dehydrogenase, carbonic anhydrase, myeloperoxidase, paraoxonase and lactate dehydrogenase were estimated in liver tissue homogenates of the groups. Results: Liver catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, lactate dehydrogenase, carbonic anhydrase and paraoxonase activities were decrease, but alkaline phosphatase, glucose6-phosphate dehydrogenase and myeloperoxidase activities were increase in diabetic rats when compared to normal rats. Conclusion: Results show that VS restored altered parameters in the liver tissue and prevented oxidative stress in diabetic rats.

Effects of olive leaf extract prepared in water on streptozotocin-induced oxidative stress and lipid peroxidation in rats

Bu çalışmada, Streptozotosin'in (STZ) neden olduğu diyabetik ratlarda su içinde hazırlanan zeytin yaprağı özütünün (OLE) antidiyabetik ve antioksidatif etkilerinin araştırması amaçlanmıştır. Çalışmamızda Atatürk Üniversitesi Tıbbi Uygulama ve Araştırma Merkezi (ATADEM)’den temin edilen ve ağırlıkları 200-215 g arasında değişen toplam 25 adet Albino Wistar erkek rat kullanıldı. Ratlar Kontrol, 0.5 g kg-1 OLE, 40 mg kg-1 STZ, 0.25 g kg-1 OLE + STZ ve 0.5 g kg-1 OLE + STZ olmak üzere beş gruba ayrıldı. 14 günlük OLE uygulama sonrası ratların karaciğer dokuları süperoksit dismutaz (SOD), glutatyon peroksidaz (GPx), glutatyon S-transferaz (GST) aktivitelerinin ve malondialdehit (MDA) seviyelerinin belirlenmesi için alındı. Kan örnekleri ise alanin transaminaz (ALT), aspartat transaminaz (AST) ve alkalen fosfataz (ALP) biyokimyasal parametrelerinin ve ek olarak glikoz seviyelerinin belirlenmesi için alındı. İstatistiksel analizler SPSS 20.0 yazılım programı kullanılarak ANOVA testi ile belirlendi. STZ ile birlikte OLE’nin iki farklı dozda oral yoldan verilmesinden sonra, diyabetik grup ile karşılaştırıldığında OLE’nin her iki doz grubunda ALP, ALT ve AST düzeylerinde önemli düşüşler gözlenmiştir (p&amp;lt;0.001). Ayrıca, sadece STZ verilen gruba kıyasla, STZ ile birlikte OLE uygulanan gruplarda SOD, GPx ve GST aktivitelerinde anlamlı bir artışla birlikte MDA, ALT, AST ve ALP düzeylerinde istatiksel olarak anlamlı düşüşler görülmüştür (p&amp;lt;0.001). Ancak OLE’nin 0.5 g kg-1 dozu 0.25 g kg-1 dozuna kıyasla daha etkili olmuştur. Sonuç olarak, elde edilen in-vivo veriler, suda hazırlanan OLE'nin oksidatif stresin kısıtlanması ve antioksidan aktivitelerin güçlendirilmesi sayesinde bir anti-diyabetik etkiye sahip olabileceğini göstermiştir.

Protective effects of peel extracts of Irvingia wombolu on metabolic disorders in streptozotocin-induced diabetic rats

BackgroundDiabetes is widely recognized as associated with several structural and functional liver, kidney, and heart abnormalities. Therefore, the present study was conducted to evaluate the protective effect of peel extracts of Irvingia wombolu against diabetes complications.MethodsDiabetes was induced by intravenous administration of streptozotocin (STZ) (50 mg/kg) through the right jugular vein on rats and animals with blood glucose values of at least 250 mg/dl received orally aqueous extract of peel (AEP), hydroethanolic extract of peel (HEP), tolbutamide and DMSO 10%. Their effects on the concentration of blood glucose, total cholesterol, HDL-C, LDL-C, triglycerides, malondialdehyde (MDA) and activities of catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in diabetic and normal rats were investigated using standard methods.ResultsTwenty-one days of treatment with AEP and HEP at a dose of 400 mg/kg significantly (P < 0,05) reduced the fasting blood glucose to a point of reaching normal value. The antihyperlipidemic assessment of extracts revealed a significant (P < 0,05) decrease in total cholesterol, triglycerides, LDL levels, and a significant (P < 0,05) increase in HDL level in the plasma of treated diabetic rats. Furthermore, plasma biomarkers of liver and kidney dysfunction were significantly reduced in treated diabetic rats. We also observed increased activities of catalase, SOD, and reduced glutathione in diabetic treated rats.ConclusionThe present findings suggest that AEP and HEP have a protective effect on liver, kidney, and heart in experimental diabetic rats which can be beneficial in the management of diabetes and its complications.

An investigation of the effects of thiamine in the experimental diabetic rat brain tissue

An investigation of the effects of thiamine in the experimental diabetic rat brain tissue

Rat pancreatectomy combined with isoprenaline or uninephrectomy as models of diabetic cardiomyopathy or nephropathy

Cardiovascular and renal complications are the predominant causes of morbidity and mortality amongst patients with diabetes. Development of novel treatments have been hampered by the lack of available animal models recapitulating the human disease. We hypothesized that experimental diabetes in rats combined with a cardiac or renal stressor, would mimic diabetic cardiomyopathy and nephropathy, respectively. Diabetes was surgically induced in male Sprague Dawley rats by 90% pancreatectomy (Px). Isoprenaline (Iso, 1 mg/kg, sc., 10 days) was administered 5 weeks after Px with the aim of inducing cardiomyopathy, and cardiac function and remodeling was assessed by echocardiography 10 weeks after surgery. Left ventricular (LV) fibrosis was quantified by Picro Sirius Red and gene expression analysis. Nephropathy was induced by Px combined with uninephrectomy (Px-UNx). Kidney function was assessed by measurement of glomerular filtration rate (GFR) and urine albumin excretion, and kidney injury was evaluated by histopathology and gene expression analysis. Px resulted in stable hyperglycemia, hypoinsulinemia, decreased C-peptide, and increased glycated hemoglobin (HbA1c) compared with sham-operated controls. Moreover, Px increased heart and LV weights and dimensions and caused a shift from α-myosin heavy chain (MHC) to β-MHC gene expression. Isoprenaline treatment, but not Px, decreased ejection fraction and induced LV fibrosis. There was no apparent interaction between Px and Iso treatment. The superimposition of Px and UNx increased GFR, indicating hyperfiltration. Compared with sham-operated controls, Px-UNx induced albuminuria and increased urine markers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and podocalyxin, concomitant with upregulated renal gene expression of NGAL and kidney injury molecule 1 (KIM-1). Whereas Px and isoprenaline separately produced clinical endpoints related to diabetic cardiomyopathy, the combination of the two did not accentuate disease development. Conversely, Px in combination with UNx resulted in several clinical hallmarks of diabetic nephropathy indicative of early disease development.

Zinc oxide nanoparticles augment CD4, CD8, and GLUT-4 expression and restrict inflammation response in streptozotocin-induced diabetic rats.

This study evaluated the biochemical, molecular, and histopathological mechanisms involved in the hypoglycaemic effect of zinc oxide nanoparticles (ZnONPs) in experimental diabetic rats. ZnONPs were prepared by the sol-gel method and characterised by scanning and transmission electron microscopy (SEM and TEM). To explore the possible hypoglycaemic and antioxidant effect of ZnONPs, rats were grouped as follows: control group, ZnONPs treated group, diabetic group, and diabetic + ZnONPs group. Upon treatment with ZnONPs, a significant alteration in the activities of superoxide dismutase, glutathione peroxidase, and the levels of insulin, haemoglobin A1c, and the expression of cluster of differentiation 4+ (CD4+), CD8+ T cells, glucose transporter type-4 (GLUT-4), tumour necrosis factor, and interleukin-6 when compared to diabetic and their control rats. ZnONPs administration to the diabetic group showed eminent blood glucose control and restoration of the biochemical profile. This raises their active role in controlling pancreas functions to improve glycaemic status as well as the inflammatory responses. Histopathological investigations showed the non-toxic and therapeutic effect of ZnONPs on the pancreas. TEM of pancreatic tissues displayed restoration of islets of Langerhans and increased insulin-secreting granules. This shows the therapeutic application of ZnONPs as a safe anti-diabetic agent and to have a potential for the control of diabetes.

Role of L-carnitine treated Mesenchymal stem cells on histological changes in spleen of experimentally induced diabetic rats and the active role of Nrf2 signaling

Introduction: Diabetes mellitus induces atrophy in splenic lymphoid follicles, which may affect the body defense mechanisms. Mesenchymal stem cells could be a practical approach to treat diabetes-induced spleen damage. Aim of work: to demonstrate the histological changes in adult albino rat's spleen after induction of diabetes and to assess the effect of injected mesenchymal stem cells (MSCs) treated with L-carnitine on alleviating these changes. Materials and Methods: Thirty adult male albino rats were divided into 3 main groups: Group I (control), Group II (diabetic): the rats were injected once with intra-peritoneal Streptozotocin (STZ) 50mg/kg and group III (Diabetic +MSCs): the animals were injected intravenously with MSCs four weeks after diabetes confirmation. All rats were sacrificed four weeks after MSC injections (8 weeks from the beginning of the experiment) and spleen specimens were processed to be examined by light microscope. Blood specimens were collected to measure glucose and insulin levels. The mRNA expression for Nrf2, IL 10 and IL 17A was measured by Real-time Polymerase Chain Reaction (RT-PCR). Results: Degenerative changes were observed in diabetic group in the form of reduced size of white pulp with many apoptotic nuclei. Widened congested red pulp, statistical significant reduction of insulin level, white pulp volume, area percent of CD4+ and nuclear factor erythroid 2 related factor 2 (Nrf2) immunoexpression and also in qRT-PCR relative gene expression of Nrf2 and IL 10. There was significant increase in blood glucose level and qRT-PCR relative gene expression of IL 17A. All changes were reversed in MSCs treated group. Conclusion: we concluded that L-carnitine pretreatment of MSCs releases a novel way to enhance MSCs therapeutic potential efficacy in spleen of experimental diabetic rats with recommendation of trying further researches for their application in other vital organs.

Early changes in myocyte contractility and cardiac function in streptozotocin-induced type 1 diabetes in rats

Diabetes can elicit direct deleterious effects on the myocardium, independent of coronary artery disease or hypertension. These cardiac disturbances are termed diabetic cardiomyopathy showing increased risk of heart failure with or without reduced ejection fraction. Presently, there is no specific treatment for this type of cardiomyopathy and in the case of type I diabetes, it may start in early childhood independent of glycemic control. We hypothesized that alterations in isolated myocyte contractility and cardiac function are present in the early stages of experimental diabetes in rats before overt changes in myocardium structure occur. Diabetes was induced by single-dose injection of streptozotocin (STZ) in rats with data collected from control and diabetic animals 3 weeks after injection. Left ventricle myocyte contractility was measured by single-cell length variation under electrical stimulation. Cardiac function and morphology were studied by high-resolution echocardiography with pulsed-wave tissue Doppler imaging (TDI) measurements and three-lead surface electrocardiogram. Triglycerides, cholesterol and liver enzyme levels were measured from plasma samples obtained from both groups. Myocardial collagen content and perivascular fibrosis of atria and ventricle were studied by histological analysis after picrosirius red staining. Diabetes resulted in altered contractility of isolated cardiac myocytes with increased contraction and relaxation time intervals. Echocardiography showed left atrium dilation, increased end-diastolic LV and posterior wall thickness, with reduced longitudinal systolic peak velocity (S’) of the septum mitral annulus at the apical four-chamber view obtained by TDI. Triglycerides, aspartate aminotransferase and alkaline phosphatase were elevated in diabetic animals. Intertitial collagen content was higher in atria of both groups and did not differ among control and diabetic animals. Perivascular intramyocardial arterioles collagen did not differ between groups. These results suggest that alterations in cardiac function are present in the early phase in this model of diabetes type 1 and occur before overt changes in myocardium structure appear as evaluated by intersticial collagen deposition and perivascular fibrosis of intramyocardial arterioles.

The Effects of Kefir on Kidney Tissues and Functions in Diabetic Rats.

This study was designed to determine the protective effect of kefir on the oxidative damage, as well as histological and biochemical changes that occur in the kidney tissues of experimental diabetic rats. Forty rats were allocated into four groups as "healthy saline" (SF), "healthy kefir" (KF), and the same groups with experimentally induced diabetes (DSF and DKF). Diabetes was induced by administering 65mg/kg single-dose streptozotocin. Oral kefir was given 10ml/kg/day for 35days to the rats in the groups KF and DKF. The same amount of saline was given to the groups SF and DSF. On the 36th day of the study, blood glucose, urea, and creatinine were measured besides glucose, creatinine, microalbuminuria, and sodium in the urine. Additionally, histological examination was performed on the kidney tissues. Blood glucose, creatinine, and urea levels were significantly lower in the DKF group compared with those of the DSF group (p < 0.001). Also, the creatinine level was significantly decreased (p < 0.001), and microalbuminuria was increased (p < 0.001) in the DKF group compared with that of the DSF group. Histologically, intermittent expansion in the renal glomeruli, reduction of cast formation in the tubules, and improvement in the renal epithelial tissues of the DKF group were observed. Kefir decreased the damage caused by diabetes. These results indicate that kefir supplementation may contribute to better control of oxidative stress, which is related to the improvement of renal functions, suggesting its use to slow down the progression of diabetic nephropathy.

The effect of Rheum ribes L. on oxidative stress in diabetic rats.

Objectives Rheum ribes L. is a perennial plant that belongs to the family of Polygonaceae, which is often used in traditional therapy because it possesses many bioactivities, such as antioxidant and antibacterial ones. Here we examined the effect of different R.ribes L. extracts on oxidative stress in experimental diabetic rats. Methods Thirty-six rats were divided into six groups as follows: group I, control group; group II, diabetic rats; group III, diabetic rats treated with the aqueous extract of R.ribes L. by gavage at 50mg/kg for 15days; group IV, diabetic rats treated by gavage with the ethanolic extract of R.ribes L. at 50mg/kg for 15days; group V, nondiabetic rats treated by gavage with the aqueous extract of R.ribes L. at 50mg/kg for 15days; group VI, nondiabetic rats treated by gavage with the ethanol extract of R.ribes L. at 50mg/kg for 15days. After 15days, the animals were sacrificed and the liver and kidney tissues of each animal were isolated. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activities in the tissue samples were measured, and histopathologic examination was carried out. Results R.ribes L. was effective in reducing the oxidative stress and increasing the levels of the antioxidant enzymes. Increased levels of MDA and decreased levels of SOD, CAT and GSH-Px were observed in both the liver and kidney tissues in group II. Decreased levels of MDA and increased levels of SOD, CAT and GSH-Px were observed in group III compared with group II. In group IV, decreased levels of MDA and increased levels of SOD, CAT and GSH-Px were observed in comparison with group II. Conclusions Diabetes increases oxidative stress and causes a decrease in antioxidant enzyme levels. Both aqueous and ethanolic extracts of R.ribes L. decrease oxidative stress activity and increase the levels of antioxidant enzymes. The ethanol extract of R.ribes L. has a higher antioxidant effect than the aqueous extract.

Effect of 8 Weeks of Incremental Endurance Training on Antioxidant Enzymes and Total Antioxidant Status of Cardiac Tissue in Experimental Diabetic Rats

Introduction: Evidence suggests increased oxidative stress and improved total antioxidant status resulting from regular exercise in the heart tissue of diabetic patients. The aim of this study was to investigate the effect of 8 weeks of increasing endurance training on the levels of antioxidant enzymes and the total antioxidant status of the cardiac tissue of diabetic mice. Methods: In this experimental study, 24 Wistar male rats (aged 10 weeks and weighing 256±11.8 g) were divided into 4 groups of 6.The training program lasted for 8 weeks with increasing endurance training. It was measured 48 hours after the completion of the protocol levels of antioxidant enzymes (catalase, glutathione, and glutathione peroxidase) and the total antioxidant status of rat heart tissue. One-way analysis of variance test was used for intergroup comparisons and Pearson test was used to investigate the relationship between indicators. Results: The results showed a significant difference in total antioxidant status, catalase and glutathione (P = 0.001) and were not significant in glutathione peroxidase (P = 0.240). Moreover, a follow-up test showed a significant increase in total antioxidant status and catalase (healthy exercise, healthy control, and diabetic exercise compared to diabetic control), Glutathione (healthy exercise (P = 0.001) and healthy control (P = 0.049) compared to diabetic control); (Healthy exercise (P = 0.003) compared to diabetic exercise. Finally, some correlations between antioxidant enzymes and total antioxidant status were significant. Conclusion: According to research results, increasing endurance training appears to increase levels of antioxidant enzymes and improve total antioxidant status, thereby it reduces oxidative stress in the heart tissue of diabetic mice.

Protective Effects of an Oxovanadium(IV) Complex with N2O2 Chelating Thiosemicarbazone on Small Intestine Injury of STZ-Diabetic Rats.

Vanadium compounds are being investigated as potential therapeutic agents in the treatment of many health problems, primarily diabetes. We aimed to provide the effect of N(1)-4-hydroxysalicylidene-N(4)-salicylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV) (VOL) on small intestinal injury in experimental male diabetic rats. Four groups were created of 3.0-3.5-month-old rats. The rats were made diabetic by a single dose of streptozotocin (STZ) at 65 mg/kg and grouped as follows: control animals, VOL-given control animals, STZ-induced diabetic animals and STZ-induced diabetic animals given VOL. A daily dose of 0.2 mM/kg vanadium complex was administered orally for 12 days after the inducement of diabetes. On the 12th day, small intestine tissue samples were taken. According to the data obtained from the biochemical analysis, reduced glutathione (GSH) level, catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), Na+/K+-ATPase and paraoxanase (PON) activities were increased, whereas sialic acid (SA), xanthine oxidase (XO) and disaccharidases (maltase and saccharidase) activities were decreased in the small intestine tissue of VOL-treated diabetic rats. Microscopic examinations revealed a remarkable decrease in the mucosal necrotic areas, discontinuity in the brush border, deterioration of the villi integrity and oedema inside the villi, but with a mild decrease in the inflammatory cells, deterioration and loss of integrity of the gland in the small intestine of VOL-treated diabetic rats. Moreover, VOL treatment markedly decreased the proliferation of villus cells and especially inflammatory cells in the small intestine of diabetic rats. According to the obtained data, the administration of VOL is a potentially convenient strategy to reducing small intestine injury in diabetic rats.