Kidney Of Streptozotocin-induced Diabetic Rats Research Articles

Antioxidant Effect of the Ethyl Acetate Extract of Potentilla indica on Kidney Mitochondria of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia. This state may lead to an increase in oxidative stress, which contributes to the development of diabetes complications, including diabetic kidney disease. Potentilla indica is a traditional medicinal herb in Asia, employed in the treatment of several diseases, including DM. In this study, we investigated the antioxidant effect of the ethyl acetate extract of Potentilla indica both in vitro and on kidneys of streptozotocin-induced diabetic male rats. Firstly, phytochemicals were identified via UPLC-MS/MS, and their in vitro antioxidant capabilities were evaluated. Subsequently, male Wistar rats were assigned into four groups: normoglycemic control, diabetic control, normoglycemic treated with the extract, and diabetic treated with the extract. At the end of the treatment, fasting blood glucose (FBG) levels, creatinine, blood urea nitrogen (BUN), and uric acid were estimated. Furthermore, the kidneys were removed and utilized for the determination of mitochondrial reactive oxygen species (ROS) production, mitochondrial respiratory chain complex activities, mitochondrial lipid peroxidation, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. The in vitro findings showed that the major phytochemicals present in the extract were phenolic compounds, which exhibited a potent antioxidant activity. Moreover, the administration of the P. indica extract reduced creatinine and BUN levels, ROS production, and lipid peroxidation and improved mitochondrial respiratory chain complex activity and GSH-Px, SODk, and CAT activities when compared to the diabetic control group. In conclusion, our data suggest that the ethyl acetate extract of Potentilla indica possesses renoprotective effects by reducing oxidative stress on the kidneys of streptozotocin-induced diabetic male rats.

Morphological changes in the kidney tissue of rats with experimental diabetes mellitus and during correction with metformin and modulators of hydrogen sulfide metabolism

Annotation. Metformin is widely used for pharmacocorrection of diabetic nephropathy in type 2 diabetes mellitus. However, the mechanisms of the protective effect of metformin on the kidneys remain unclear, in particular, the contribution of the hydrogen sulfide system to metformin’s nephroprotective effect is unknown. Therefore, the aim of our study was to assess the role of metformin and its combination with modulators of hydrogen sulfide metabolism in the correction of histological changes in the kidneys of streptozotocin-induced diabetic rats. The studies were performed on 30 white non-linear male rats, which were divided into five groups: 1 group - control; group 2 – animals with experimental diabetes, which was initiated by a single intraperitoneal injection of streptozotocin (40 mg/kg of weight) in 0.1 M citrate buffer (pH 4.5); Group 3 - animals with experimental diabetes, which were treated with metformin (500 mg/kg/day, intragastrically) from the 3rd to the 28th day; Group 4 - animals with diabetes mellitus, which, along with metformin, were administered NaHS (56 μmol/kg/day, intragastrically); Group 5 - animals with diabetes mellitus, which, along with metformin, were administered propargylglycine (442 μmol/kg/day, intragastrically). Histological examinations were performed according to generally accepted methods using an Olympus BX-41 light microscope (Olympus Europe GmbH, Japan). It was found that animals with experimental diabetes develop nephrosclerosis and glomerular hypertrophy, damage to the endothelium of kidney vessels, interstitial inflammation, and edema, and dystrophic and necrobiotic changes in the glomeruli. The administration of metformin to diabetic animals reduced the severity of nephrosclerosis, glomerular hypertrophy, destruction of vascular endotheliocytes, inflammation, and damage to the glomerular apparatus. The use of the hydrogen sulfide donor NaHS increased the nephroprotective activity of metformin, while the introduction of the hydrogen sulfide synthesis inhibitor- propargylglycine, significantly reduced the protective effect of metformin on the kidneys. The obtained results of the histological examination justify the feasibility of implementation of a hydrogen sulfide donor in order to potentiate the renoprotective effect of metformin.

Protective Effect of Chitosan Extracted from Freshwater Crab Sartoriana spinigera (Wood-Mason, 1871) on the Histological Changes in the Kidneys of Streptozotocin-Induced Diabetic Rats

Protective Effect of Chitosan Extracted from Freshwater Crab Sartoriana spinigera (Wood-Mason, 1871) on the Histological Changes in the Kidneys of Streptozotocin-Induced Diabetic Rats

Attenuation of the cytotoxic, nephrotoxic and hepatotoxic effects of streptozotocin-induced diabetic rats by aqueous extract of Lepidium sativum L. (Brassicaceae)

Diabetes mellitus is a health condition whose major feature is hyperglycemia that arises from various etiologies. Diabetes mellitus is connected with constraints in the metabolism of proteins and lipids which leads to complications such as hepatopathy, nephropathy, retinopathy and vasculopathy. Plant resources are utilized for better beneficial curative molecules, minimal side effects and cost. Lepidium sativum (garden cress) is a plant whose parts have been reportedly employed in the treatment of conditions like inflammation, diabetes, pyretism, hemorrhage and hypertension. This histopathological study sought to investigate the effect of the aqueous extract of L. sativum on the tissues of the pancreas, kidney, and liver in streptozotocin-induced diabetic rats. Haematoxylin and Eosin Staining method of histopathology was employed and the cytotoxic, nephrotoxic and hepatoxic effects on the pancreatic Islet cells, kidney and liver were attenuated on treatment with different doses of aqueous extracts of L. sativum plant.

Immunohistochemical Effects of Ethyl Acetate Fraction of Lycopersicum Esculentus on the Kidney in Experimentally Induced Diabetic Wistar Rats

Diabetic nephropathy (DN) as a leading cause of end-stage renal failure which has become source of concern recently. The aim of this study was to investigate the effect of EAFL on the histomorphology and evaluate its effect on inflammatory markers in Streptozotocin- Induced diabetic Wistar rats. This study was conducted using thirty male Wistar rats. The animals were divided into five groups of 6 rats each (n=6). Group A was the control animals ( administered with 20 ml/kg/day of citrate buffer orally (p.o) stat for 4 weeks. Group B was induced with 65 mg/kg of streptozotocin in citrate buffer intraperitoneally stat and observe for four weeks without treatment. Group C,D and E were the test groups that received 65 mg/kg of streptozotocin in citrate buffer intraperitoneally stat and 20, 40 and 60 mg/kg/day of EAFL respectively for four weeks after induction of diabetes. Descriptive and inferential statistics were used to analyze the data. The results showed reduction in serum insulin levels in diabetic groups which was reversed to normal when the intervening agent (EAFL) was administered. The histology of the kidneys showed distortion in renal corpuscles which was reversed when EAFL was administered. The immunohistochemistry of kidney tissues in the normal group (A) showed areas of Ag-Ab immunological reactivity, however, there was no reactivity in the diabetic groups. The study concluded that EAFL has anti glycemic and anti inflammatory effect on the kidneys of Streptozotocininduced diabetic Wistar rats.

Geraniol Attenuates Oxidative Stress and Apoptosis in the Liver and Kidney of Streptozotocin-Induced Diabetic Rats

a peer-reviewed, open access online international journal which publishes original research papers. The journal welcomes submission from scholars and experts for possible publication from all over the world. The scope of the journal includes: Pharmaceutical research, chemistry and biochemistry of naturally occurring compounds, biological evaluation of crude extracts, ethnomedicine, traditional and complementary medicine, ethnopharmacology, biomedical research, Biotechnology, Evaluation of natural substances of land and sea and of plants, microbes and animals, pharmacognosy, bioavailability, clinical, pharmacological, toxicological studies and pharmacokinetics of phytochemicals, Isolation and characterization of compounds, structure elucidation, synthesis and experimental biosynthesis of natural Product as well as developments of methods in these areas are welcomed in the journal.

Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic Rat Kidneys.

Background: The aim of this study was to determine the expression of epithelial to mesenchymal transition (EMT)-related transcription factors Snail, Wnt4, and Notch2 with key roles in renal fibrosis, in different renal areas of diabetic rats: glomeruli (G), proximal and distal convoluted tubules (PCT; DCT). Methods: Male Sprague Dawley rats were instilled with 55 mg/kg streptozotocin (diabetes mellitus type I model, DM group) or citrate buffer (control group). Kidney samples were collected 2 weeks and 2 months after DM induction and processed for immunohistochemistry. Results: Diabetic animals showed higher Wnt4 kidney expression both 2 weeks and 2 months post-DM induction, while Snail expression significantly increased only 2 weeks after DM initiation (p < 0.0001). We determined significantly higher expression of examined EMT-related genes in different kidney regions in diabetic animals compared with controls. The most substantial differences were observed in tubular epithelial cells in the period of 2 weeks after induction, with higher Snail and Wnt4 expression in PCT and increased Snail and Notch2 expression in DCT of diabetic animals (p < 0.0001; p < 0.001). Conclusion: The obtained results point to the EMT-related factors Snail, Wnt4, and Notch2 as a potential contributor to diabetic nephropathy development and progression. Changes in their expression, especially in PCT and DCT, could serve as diagnostic biomarkers for the early stages of DM and might be a promising novel therapeutic target in this condition.

Effects of Melatonin on Hepatic and Renal Complication of Diabetes

Background &amp; Objective: Diabetes is associated with biochemical and pathological changes in liver and kidney tissue. One of the most important mechanisms in causing complications of diabetes is increasing the production of free radicals due to impaired glucose metabolism. Some studies have shown that melatonin is effective in protecting tissues due to its antioxidant role. The aim of this study was to evaluate the effect of melatonin on biochemical factors, histopathological changes of liver and kidney in streptozotocin-induced (STZ) diabetic rats.&#x0D; Materials &amp; Methods: In this experimental study, 40 adult male rats were randomly divided into 4 groups (n=10): control group, diabetic group, melatonin group (20mg/kg BW) and melatonin + diabetic group. At the end of the 6th week, blood samples were collected. Biomarkers of liver function (alkaline phosphatase: ALP, aspartate aminotransferase: AST, alanine aminoteransferase: ALT) and kidney biomarkers (urea, uric acid, BUN, creatinine), serum glucose and histopathological changes of these tissues were evaluated. Data analysis was performed using SPSS and the significance level was P&lt;0.05.&#x0D; Results: Melatonin treatment significantly (P&lt;0.05) reduced hyperglycemia, hepatic enzymes and renal biochemical factors due to diabetes and improved histopathological changes of liver and kidney tissue.&#x0D; Conclusions: Melatonin consumption can be effective in improving the renal and kidney complications of diabetes.

Effects of Creatine Supplementation on Histopathological and Biochemical Parameters in the Kidney and Pancreas of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a worldwide health concern, and projections state that cases will reach 578 million by 2030. Adjuvant therapies that can help the standard treatment and mitigate DM effects are necessary, especially those using nutritional supplements to improve glycemic control. Previous studies suggest creatine supplementation as a possible adjuvant therapy for DM, but they lack the evaluation of potential morphological parameters alterations and tissue injury caused by this compound. The present study aimed to elucidate clinical, histomorphometric, and histopathological consequences and the cellular oxidative alterations of creatine supplementation in streptozotocin (STZ)-induced type 1 DM rats. We could estimate whether the findings are due to DM or the supplementation from a factorial experimental design. Although creatine supplementation attenuated some biochemical parameters, the morphological analyses of pancreatic and renal tissues made clear that the supplementation did not improve the STZ-induced DM1 injuries. Moreover, creatine-supplemented non-diabetic animals were diagnosed with pancreatitis and showed renal tubular necrosis. Therefore, even in the absence of clinical symptoms and unaltered biochemical parameters, creatine supplementation as adjuvant therapy for DM should be carefully evaluated.

Ameliorative property of Sesbania grandiflora on carbohydrate metabolic enzymes in the liver and kidney of streptozotocin-induced diabetic rats.

In diabetic condition, endogenous glucose synthesis will be elevated due to defect in the action of vital enzymes involved in carbohydrate metabolism, which is the main cause for hyperglycemia. The current study was designed to explore the anti-hyperglycemic efficacy of Sesbania grandiflora flower (SGF) extract by evaluating the concentration of C-peptide, insulin, glucose, glycosylated hemoglobin (HbA1C), hemoglobin (Hb), glycogen and carbohydrate metabolic enzymes activities in diabetic rats. The study found to lower the level of glucose, HbA1C and simultaneously ameliorated concentrations of C-peptide, insulin, hemoglobin (Hb), glycogen and carbohydrate metabolic enzymes activities in SGF treated (250 mg/kg body weight for 45 days) diabetic rats. Moreover, SGF administered diabetic rats showed diminished consumption of food and water at the same time improved body weight. The results obtained from the present study were compared with glibenclamide treated (600 µg/kg body weight) diabetic rats. SGF were supplemented to normal rats to rule out toxic effect of SGF, to explore any significant alteration in the above parameters. Hence, the results depict that SGF modulated the carbohydrate metabolic enzymes activities through ameliorating the secretion of insulin and diminishing the level of glucose concentration in STZ-induced diabetic rats by its bioactive compounds.

Antioxidant Activity of the Ethyl Acetate Extract of Potentilla indica on Kidneys of Streptozotocin‐Induced Diabetic Rats

Diabetes mellitus is a chronic-degenerative disease characterized by chronic hyperglycemia. This condition may lead to an increase of the oxidative stress, which contributes to the development of diabetes complications including diabetic kidney disease. Several studies have addressed the antioxidant effects of a wide range of plant extracts in the treatment of diabetes. Potentilla indica is a traditional herbal medicine in Asia, employed in the treatment of several diseases including diabetes, due to its secondary metabolites with bioactive functions such as antioxidant activity. Therefore, we hypothesize that the ethyl acetate extract of Potentilla indica decreases the oxidative stress on kidneys of streptozotocin-Induced diabetic rats improving the diabetic condition. Objective The present study aimed to investigate the antioxidant activity of the ethyl acetate extract of Potentilla indica on kidneys of streptozotocin-induced diabetic male rats. Methods In this research we assessment the antioxidant activity of the ethyl acetate extract of Potentilla indica by employing in vitro assays to measure its protective effect on lipid peroxidation and ferric reducing antioxidant power. We also tasted the extract in male Wistar rats (300-350 g), which were randomly divided into 4 groups: normoglycemic control, diabetic control, normoglycemic treated with the extract and diabetic treated with the extract. All groups were administered orally once daily for 60 days with the vehicle for the control groups and with the ethyl acetate extract of P. indica (25 mg/Kg) for the treated groups, respectively. After 60 days of treatment, rats were euthanized to obtain homogenate and mitochondria of kidney, which were used for the determination of mitochondrial respiratory chain complex activities, reactive oxygen species (ROS) production, lipid peroxidation and catalase activity. Results The ethyl acetate extract of Potentilla indica possessed in vitro antioxidant activity at different concentrations in contrast with Trolox as positive control. Furthermore, in the treated diabetic group, the extract reduced lipid peroxidation, ROS production, and restored mitochondrial respiratory chain complexes and catalase activities when compared with diabetic control group. Conclusion Our data suggest that the ethyl acetate extract of Potentilla indica possessed both in vitro as in vivo antioxidant activity on kidneys of streptozotocin-induced diabetic rats.

Immunohistochemical Expression Pattern of Mismatch Repair Genes in the Short-term Streptozotocin-induced Diabetic Rat Kidneys.

We studied the expression of mismatch repair genes (MMRs)-mutS protein homolog 2 (MSH2), PMS2, MutL homolog 1 (MLH1), and yH2AFX in diabetic rat kidneys. Streptozotocin-induced diabetes mellitus type 1 rat model (DM1) was used. Renal samples were collected 2 weeks and 2 months after DM1 induction and immunohistochemical expression of MMR genes in the renal cortex was analyzed. Diabetic animals showed lower MSH2 and higher yH2AFX kidney expression both 2 weeks and 2 months after DM1 induction. MLH1 expression significantly increased 2 weeks after DM1 induction (P<0.0001). The most substantial differences were observed in the period 2 weeks after induction, with lower MSH2 and higher MLH1 expression in the proximal convoluted tubules and distal convoluted tubules (DCT) of diabetic animals (P<0.001). yH2AFX expression significantly increased in the DCT of diabetic animals at both time points (P<0.001; P<0.01). PMS2 expression changed only in the glomeruli, where it significantly decreased 2 months after DM1 induction (P<0.05). We concluded that the most substantial changes in renal expression of MMRs are happening already 2 weeks after diabetes induction, predominantly in the proximal convoluted tubules and DCT. Moreover, DCT could have a critical role in the pathophysiology of diabetic nephropathy (DN) and might be a future therapeutic target in this condition. The obtained results point to the MMRs as a potential factor in the development and progression of DN, as well as the possible link between DN and renal carcinogenesis.

Effect of Adhatoda zeylanica Ethanolic Extract on Attenuated Kidney in Streptozotocin-Induced Diabetic Rats

AbstractObjective The present study was aimed to evaluate the effect of ethanolic extract of Adhatoda zeylanica (EAZ) leaves on streptozotocin (STZ)-induced diabetes mellitus (DM) and its renal complications in male Wistar albino rats.Materials and Methods Adult male Wistar albino rats were randomly selected from a colony, divided into four groups, namely, A, B, C, and D, with each having six rats (n = 6) and each weighing between 200 and 250 g. Group A served as control and received only water per oral (p.o.). Group B, C, and D animals received a single dose of STZ at 45 mg/kg body weight (kbw) intraperitoneal administration (i.p.) on day 1 and observed for fasting blood glucose (FBG) to induce DM for next 72 hours. After the DM was induced, group B served as DM control, group C received the standard drug glibenclamide (GL) at 5 mg/kbw p.o. once daily, and group D received EAZ of 500 mg/kbw p.o. once daily for 35 days. After the observation period, the animals were euthanized, serum creatinine and blood urea, antioxidants in the kidney tissue homogenate, and histopathological studies were assessed to know the ameliorative effect of the test drugs.Results Renal parameters, such as serum creatinine, blood urea, antioxidants activities, in group D were nearer to the control when compared with groups B and C. Histopathological studies revealed that there was minimal renal damage in group D when compared with groups B and C.Conclusion Administration of ethanolic EAZ showed significant ameliorative effects on the FBG, biochemical, oxidative, and histopathological parameters on kidney tissues treated with STZ to induce DM.

The Comparison of Antioxidant Effect of Aspirin, Metformin, Atorvastatin and Captopril Co-administration in the Heart and Kidney Tissues of Diabetic Rats.

The present study investigated the effects of co-administration of aspirin, metformin, atorvastatin and captopril on serum lipid profile and oxidative stress in the heart and kidney of streptozotocin-induced diabetic rats. In this study, rats were randomly divided into the following eleven groups: control (Cont.), and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg), or atorvastatin (AT, 40 mg/kg), as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA), and (D + M + C + AT + ASA). The rats in treatment groups daily received drugs by gavage for six weeks. Finally, serum lipid profile and levels of oxidative markers in the heart and kidney tissues were evaluated. In diabetic rats, blood levels of glucose, cholesterol, TG (triglyceride), LDL (low-density lipoprotein), MDA (malondialdehyde) and AIP (atherogenic index of plasma) significantly increased but those of HDL (high-density lipoprotein) and total thiol as well as SOD (superoxide dismutase) and CAT (catalase) activities significantly decreased. Treatment with different combinations of C, ASA, AT and M significantly ameliorated these parameters. This study showed that co-administration of ASA, M, C and AT, could improve glucose and lipid metabolism and oxidative stress markers in the kidneys and heart tissues of diabetic rats more markedly than the administration of these drugs alone.

Curculigo pilosa mitigates against oxidative stress and structural derangements in pancreas and kidney of streptozotocin-induced diabetic rats.

Background Curculigo pilosa (African crocus) is widely used in folklore medicine to treat diabetes mellitus and its associated complications. This study was carried out to evaluate this traditional claim by mechanistic investigation of the effect of corn steep liquor extract of Curculigo pilosa and its n-butanol and methanol solvent fractions on hyperglycemia mediated oxidative damage in pancreas and kidney of streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced by single intraperitoneal administration of (50 mg/kg) streptozotocin and diabetic rats were treated orally with the extract(s) once in a day for 28 days. After experimental period, the effect of the extract(s) on hyperglycemia mediated oxidative stress was assessed by determination of lipid peroxidation (LPO), reduced glutathione (GSH), nitric oxide (NO), hydrogen peroxide (H2O2) and activities of catalase (CAT) and superoxide dismutase (SOD) enzymes. Also histopathology studies were conducted to substantiate the protective effects on pancreas and kidney. Results Oral administration of the extract significantly (p<0.05) mitigated the hyperglycemia mediated oxidative damage via improving the antioxidant system, inhibit the generation of lipid peroxide, hydrogen peroxide and nitric oxide. Also administration of extracts improved the structural architecture of the pancreas and kidney tissues in diabetic rats. Conclusion The results obtained in this study provide resounding scientific support for the folkloric use of Curculigo pilosa in the management of diabetes mellitus and its complications.

Expression pattern of apoptosis-inducing factor in the kidneys of streptozotocin-induced diabetic rats

BackgroundIt is believed that tubulo-interstitial fibrosis and atrophy in diabetic patients are directly associated with the progression of chronic kidney disease, CKD. AIF is one of the crucial factors responsible for mitochondrial apoptosis, however, it can also promote cell survival independently from its role in apoptosis, and therefore can be potentially used as a tool in prevention of the onset of CKD in diabetic patients. Our aim was to investigate the significance of AIF expression in the development of CKD by observing the expression of AIF in 2 weeks’ and 2 months’ kidneys of diabetic rats compared to their controls. MethodsMale Sprague–Dawley rats were treated with 55 mg/kg streptozotocin (model of type 1 diabetes mellitus; DM group) or citrate buffer (control). After 2 weeks and 2 months kidney samples were collected and analysed in different renal areas. ResultsCharacteristic morphologic changes were found between the 2 months’ control and 2 months’ diabetic groups. Those changes, including fibrosis and possible replacement of podocytes with connective tissue were mainly present in the glomeruli. AIF expression was seen in the both cortex, and in the collecting ducts of the medulla. Strong intensity of AIF expression was seen in proximal and distal convoluted tubules in both diabetic groups. In the control groups the glomeruli showed no AIF staining but moderate staining was seen in both diabetic groups. Overall, the percentage of AIF positive cells in the glomeruli was the lowest. The greatest rise in cell positivity was displayed from the 2 weeks’ control group to 2 weeks’ diabetes group (38 %) in glomeruli. The cell positivity of the 2 weeks’ diabetic group is significantly reduced to 18 % in the 2 months’ diabetic group in glomeruli. A similar pattern was seen in the proximal tubular cells (92 % positivity 2 weeks diabetic groups; 89 % positivity 2 months diabetic groups), as well as in the distal tubules. The highest percentage of AIF positive cells was seen in the collecting ducts, more than 80 % in all groups. ConclusionsOur study provides insight into AIF expression pattern during short term diabetes model, confirming possible dual role of AIF, not only in apoptosis but also in cell function and homeostasis, and proving AIF as potential therapeutic target and marker of advancement of CKD.

Ruellia tuberosa L. Extract Improves Histopathology and Lowers Malondialdehyde Levels and TNF Alpha Expression in the Kidney of Streptozotocin-Induced Diabetic Rats.

Ruellia tuberosa L. is a therapeutic plant that is generally consumed in Indonesian traditional medicine to prevent or cure various illnesses, i.e., diabetes. The current study was conducted to investigate the effects of hydroethanolic root extracts of Ruellia tuberosa L. on the kidney of streptozotocin-induced diabetic Wistar rats. In this study, male Wistar rats were divided into 5 groups: healthy rats (group 1), diabetic rats (group 2), and treated rats which received extract at dosages of 250 (group 3), 375 (group 4), and 500 (group 5) mg/kg body weight for 21 days. Diabetes mellitus was experimentally induced by the administration of five doses of streptozotocin 20 mg/kg body weight within five consecutive days. Significant increases in the value of TNF alpha expression and malondialdehyde (MDA) levels were observed in streptozotocin-induced diabetes rats. Furthermore, severe histological alterations of kidney tissues occurred in the diabetic rats group. After treatment was applied, the value of TNF alpha expression and MDA levels on the kidney decreased considerably (p < 0.05) in groups 3, 4, and 5. The optimum dosage was obtained at a dose of 250 mg/kg body weight (group 3), which had 42.24% and 52.70% decrease in TNF alpha expression and MDA levels, respectively. The histopathological profiles of the kidney also showed significant improvements in treated groups. The most prominent recoveries were also shown in group 3. The treatments induced repairment in the glomerular and renal tubular damages in the kidney tissues. To conclude, these results emphasize potentially health valuable properties of hydroethanolic root extracts of R. tuberosa L. in rats with streptozotocin-induced diabetes.

Synthesis and characterization of [125I]TZ6544, a promising radioligand for investigating sphingosine-1-phosphate receptor 2

IntroductionSphingosine-1-phosphate receptor 2 (S1PR2) activation exerts a critical role in biological abnormalities and diseases. A suitable radiotracer will advance our understanding of S1PR2 pathophysiology of diseases. The objective of this study is to evaluate the potential of iodine-125 labeled [125I]TZ6544 to be used for screening new compounds binding toward S1PR2, and assessing the changes of S1PR2 expression in the kidney of streptozotocin-induced diabetic rats. Methods[125I]TZ6544 was synthesized from borate precursor by copper (II)-catalyzed iodization reaction with [125I]NaI. [125I]TZ6544 was characterized using human recombinant S1PR2 cell membrane and biodistribution studies of [125]TZ6544 were performed on Wistar rats that were euthanized at 5 and 30 min post-injection. A rat model of diabetes was induced by IV injection of streptozotocin (55 mg/kg). In vitro autoradiography studies, immunostaining, and enzyme-linked immunosorbent assay (ELISA) analysis were performed in both diabetic and control rats. ResultsRadiosynthesis of [125I]TZ6544 was achieved successfully with good radiochemical yields of ~47% and high radiochemical purity of >99%. [125I]TZ6544 is a potent ligand in vitro for S1PR2 with Kd value of 4.31 nM. [125I]TZ6544 and [32P]-labeled endogenous S1P provided comparable IC50 values in radioactive competitive binding assays against known S1PR2 ligands. Compared to control, the kidney of diabetic rats had increased uptake of [125I]TZ6544, which could be reduced by a S1PR2 antagonist, JTE-013. Immunostaining and ELISA analysis confirmed that the diabetic rat had increased S1PR2 expression in the kidney. Conclusions[125I]TZ6544 was synthesized successfully in high yields, and in vitro evaluation suggested [125I]TZ6544 has high potential to be used for screening new S1PR2 compounds and investigating the pathophysiology of S1PR2 functions. The availability of [125I]TZ6544 may facilitate the development of therapeutics and imaging agents targeting S1PR2. Advances in knowledge[125I]TZ6544 showed increased expression of S1PR2 in diabetic rat kidney and can be used to determine binding potency of S1PR2 compounds.

Reducing Effects of Aerobic Exercise Training Combined with Berberine Chloride Supplementation on the Apoptotic Markers of Kidney in Streptozotocin-Induced Diabetic Male Rats

Objectives: The present study aimed at evaluating the effects of aerobic exercise training (ET) and different doses of berberine chloride (BC) supplementation on apoptotic indices in renal tissue of streptozotocin (STZ)-induced diabetic Wistar rats. Methods: In the current study, 64 Wistar rats were divided into two normal and diabetic groups and then the normal group was divided into two subgroups including normal control (NC) and normal exercise training (NET, 3 d/wk, 50% - 55% of VO2max for six weeks) and the diabetic group was divided into six subgroups including diabetic control (DC), diabetic exercise training (DET), diabetic BC15 (DBC: 15 mg/kg), diabetic BC30 (DBC: 30 mg/kg), diabetic BC15+ET (DBC15+ET), and diabetic BC30+ET (DBC30+ET). Intraperitoneal injection of STZ (100 mM citrate buffer, pH 4.5 contained 60 mg/kg STZ) was used for diabetes induction. Results: There was no significant difference in the levels of caspase-3 and Bax protein between the NC and DC groups (P = 0.59 and P = 0.49, respectively). The diabetic rats treated with BC30+ET demonstrated a reduction in caspase-3 compared with NC, DC, DBC15, and NET groups (P = 0.001, P = 0.02, P = 0.001, and P = 0.04, respectively). The results also revealed no significant difference in Bcl-2 protein level after six weeks of ET and BC supplementation in renal tissue of the studied groups (P = 0.33). Conclusions: These results suggested that aerobic exercise training combined with higher doses of BC could decrease pro-apoptotic indices with an increase in Bcl-2 to Bax ratio and suppress apoptotic cell death in the renal tissue of diabetic rats.

The Effects of Urtica dioica and Lamium album Extracts on the Expression Level of Cyclooxygenase-2 and Caspase-3 in the Liver and Kidney of Streptozotocin-Induced Diabetic Rats

Background: Diabetes seems to be associated with increased inflammation and induced apoptosis in several tissues. Urtica dioica and Lamium album have shown to possess a variety of beneficial properties like anti-inflammatory effects. In this experimental study, we tried to evaluate the effects of U. dioica and L. album extracts on the expression level of cyclooxygenase-2 (COX-2; as an inflammation marker) and caspase-3 (CASP-3; as an apoptotic marker) in the liver and kidney tissues of diabetic rats. Methods: Thirty-two male Wistar rats were randomly allocated to four groups: normal control, diabetic control, diabetic treated with U. dioica (100 mg/kg/daily), and diabetic treated with L. album (100 mg/kg/daily) for 28 days. At the end of the study, liver and kidney tissues were harvested and mRNA expression level of COX-2 and CASP-3 was determined by real-time PCR technique. Also, serum glucose was measured. Results: Liver COX-2 mRNA in diabetic rats was significantly higher than normal control rats (P=0.02). However, U. dioica and L. album caused significant decrease in mRNA expression of liver COX-2 in diabetic rats (P=0.015 and P=0.03, respectively). Also, in diabetic rats treated with both extracts, serum glucose was remarkably lower than diabetic control rats (P&lt;0.0001 and P&lt;0.01, respectively). Conclusion: It appears that U. dioica and L. album might decrease liver damage by decreasing the inflammatory effects of COX-2 in streptozocin-induced diabetic rats. Since these plant extracts may influence diabetes by several mechanisms, further research in this field is warranted.