Kidney Tissues Of Diabetic Rats Research Articles

Investigating the Effects of 8 Weeks of Resistance Training on the Levels of P53 and Nrf2 Proteins in Kidney Tissue in Diabetic Rats with Morphine Withdrawal Syndrome

Introduction: The effect of exercise training on kidney tissue in the condition of diabetes with morphine withdrawal syndrome is unclear. The aim of this study was to investigate the effect of 8 weeks of resistance training on the levels of P53 and Nrf2 proteins in kidney tissue in diabetic male rats with morphine withdrawal syndrome.
 Methods: This experimental study utilized a sample of 32 Wistar rats. Following the induction of diabetes, the Wistar rats were randomly divided into four groups of eight based on their weight: diabetes, morphine diabetes, diabetes with resistance training, and morphine diabetes with resistance training. The oral technique was employed for a duration of 21 days to establish a reliance on morphine.. The resistance training protocol was implemented for 8 weeks. At the end, all mice were anesthetized, killed and their tissue was extracted. The variable protein levels of this study were measured by ELISA kits. Data were analyzed using one-way analysis of variance and Tukey's post hoc test with the help of SPSS version 16 software at a significance level of p ≤ 0.05.
 Results: Resistance training caused a significant decrease in P53 in the groups of diabetes + resistance training (P=0.006) compared to diabetes and morphine diabetes + resistance training (P=0.012) compared to morphine diabetes group. Similarly, a significant decrease in Nrf2 was observed in the morphine diabetes + resistance training group (P=0.013) compared to the morphine diabetes group.
 Conclusion: Resistance training probably reduced kidney tissue damage in diabetic and diabetic rats with withdrawal syndrome by reducing P53 protein, which indicates the protective effect of resistance training on kidney tissue in pathological conditions.

Sea cucumber (Holothuria nobilis) hydrolysates improve diabetic nephropathy via suppression of oxidative stress in high-fat diet/streptozotocin-induced diabetic rats

Diabetic nephropathy (DN) is one of the most serious complications of diabetes. The purpose of the present study was to investigate the renoprotective effects of sea cucumber hydrolysates (SCH) produced using enzyme mixture of papain and protamex in diabetic rats and further to explore the underlying anti-oxidation mechanisms of peptides. Results showed that the activities of GSH-px and SOD were markedly increased by 16.97 % and 52.97 % respectively after SCH administration. Moreover, SCH increased the protein expression of NQO1, Akt, Nrf2 in kidney tissue of diabetic rats. Furthermore, 13 novel peptides were identified and further synthesized. Molecular docking analysis revealed that these peptides such as WWGP and APGY might directly bind to Keap1 through hydrogen bond, π-π bond or π-donor hydrogen bond, and thus modulate Akt/Nrf2 pathway. In summary, these findings suggested that SCH ameliorated oxidative stress by triggering Akt/Nrf2 signaling pathway, indicating that SCH may possess anti-diabetic nephropathy effects.

Chemical characterisation and appraisal of antidiabetic potential of Terminalia citrina extract in streptozotocin induced hyperglycaemia in Wistar rats

The current research was aimed to evaluate the antidiabetic activity of Terminalia citrina methanolic extract (TCME) by streptozotocin-induced diabetes in male Wistar rats. TCME exhibited better in-vitro antioxidant and alpha-amylase inhibitory activity as compared to other tested extracts. TCME at 250, 500, and 750 mg/kg showed notable (p < .05) antidiabetic potential by lowering fasting blood glucose level, restoring lipid level, serum amylase, HbA1c, kidney, and liver function tests as coevidenced from histological findings of the liver, pancreas, and kidney. TCME remarkably reinstated the antioxidant enzymatic activities (CAT: 0.181 ± 0.011 IU/mg protein, SOD: 21.45 ± 1.53 IU/mg protein) and reduced lipid peroxidation level (40.60 ± 2.41 µM/mg protein) in the liver and kidney tissue of diabetic rats at 750 mg/kg dose. The acute and subacute oral toxicity study of TCME exhibited no clinical toxicity signs and mortality. Its GC-MS spectrum unveiled the existence of 10-octadecenoic acid and other compounds which might have contributed to antidiabetic potential.

Phytochemicals of Periploca aphylla Dcne. ameliorated streptozotocin-induced diabetes in rat

BackgroundPeriploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats.MethodsThe present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols.ResultsHPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide.ConclusionThe result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.

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.

Evaluation of Anti-diabetic, Hepatoprotective and Antilipidemic Potentials of Syzygium aromaticum (Clove) on Albino Rats

Aims: The aim of this study was to evaluate the anti-diabetic, hepatorenoprotective and antilipidemic potentials of Syzygium aromaticum (clove) in albino rats.&#x0D; Study Design: This study is a non-randomized experimental study.&#x0D; Place and Duration of Study: Department of Medical Laboratory Technology, University of Port Harcourt, Nigeria, between September, 2019 and December, 2019.&#x0D; Methodology: Thirty-five male Wister rats with weight between 145 to 150 g were randomly selected into seven groups of five rats each. The first group served as Negative control (group 1). The second group was the positive control (Diabetic group). The remaining five groups being the treatment groups (3-7). Diabetes was induced intraperitoneally with 65 mg/kg of streptozotocin (STZ) single dose. Group 3 Diabetic group treated with metformin (100 mg/kg); Group 4 Diabetic group treated with low dose clove (250 mg/kg). Group 5 Diabetic group treated with low dose clove and metformin; Group 6 Diabetic group treated with high dose clove (750 mg/kg), while Group 7 were Diabetic group treated with high dose clove (750 mg/kg) and metformin for six weeks. Blood samples were collected via cardiac puncture in appropriate EDTA, heparinized and sterile bottles for standard laboratory investigations of lipid profile, glucose, liver enzymes, urea and creatinine. Plasma lipid profile, liver enzymes, urea and creatinine were determined using enzymatic end point method under standard operating procedures. Statistical analysis was done using Graph Pad Prism Version 5.03 and p values less than 0.05 were considered statistically significant.&#x0D; Results: Results revealed that the STZ-induced diabetic group exhibited highly significant increase in activity of liver enzymes AST, ALT and ALP, increase in the levels of urea, creatinine, glucose and most lipid profile parameters as compared to the negative control group (p&lt;0.001). Histopathological examination of liver and kidney tissues of diabetic rats indicated slight changes. However, their changes were overcame by clove treatment and the majority of the cells tend to be normal. Low dose clove group 5 (250 mg/kg) with metformin decreased the levels of the analytes most when compared to the levels of the positive control group. For glucose, group 5 gave a mean glucose level of 4.40 ± 1.08 mmo/l, significantly lower than the positive control group 39.67 ± 0.67, ALT group 5 gave a mean ALT level of 56.00 ± 7.11, which was significantly lower than the positive control group 205.70 ± 14.79, for urea group 5 gave a mean urea level of 4.25 ± 0.77 which was significantly lower the control group 23.80 ± 3.56 at p &lt; 0.001, thereby yielding a better treatment result.&#x0D; Conclusion: In conclusion, low dose clove supplementation with metformin could be excellent adjuvant support in the therapy of diabetes mellitus and its complications.

Protective effect of pristine C60 fullerene nanoparticle in combination with curcumin against hyperglycemia-induced kidney damage in diabetes caused by streptozotocin.

The present study aims to examine the protective effects of C60 fullerene (C60), Curcumin (CUR; Curcuma longa), C60+CUR combination against oxidative stress, apoptosis, and changes in cellular level in kidney tissue of diabetic rats. Treatment practices were administered separately to groups for 8weeks following the approval of diabetes induction. It was observed that the treatment groups had increased antioxidant potential, decreased oxidative stress levels, decreased cholesterol, alpha tocopherol, retinol levels along with improved important changes in fatty acid metabolism compared with the diabetic group. C60, CUR, and C60+CUR were also determined to act in the direction of reducing kidney damage by activating apoptotic pathways. It can be concluded based on these findings that C60, CUR, and especially C60+CUR combination has beneficial properties in maintaining kidney tissue and function by effectively preventing oxidative stress, apoptotic changes, and changes at the cellular level in kidney tissue under hyperglycemia conditions. PRACTICAL APPLICATIONS: C60 and CUR have various biological activities which can be indicated as antioxidant, anti-inflammatory, anticancer, neuroprotective, and hepatoprotective. It has been reported that C60 and CUR protect the cells against oxidative injury brought about by reactive oxygen species (ROS). Data acquired from the present study puts forth that C60 and C60+CUR may be promising agents to prevent damage induced by hyperglycemic conditions in kidney tissue.

The Effect of Aqueous Extract of Pine Kindling on the Liver and Kidney Tissues of Diabetic Rats

This study aimed to investigate the effect of aqueous extracts from the obtained kindling wood of pine trees on liver and kidney tissues in diabetes induced by streptozotocin in rats. Male Sprague Dawley rats were divided into five groups: 1) Controls, 2) STZ rats 3) STZ rats treated with aqueous extracts from the obtained kindling wood of pine trees (different doses) for 10 weeks. According to our results, it was determined that these extracts show beneficial effects on oxidative stress in liver and kidney tissues. In vitro studies, bovine, porcine pancreas, fungi and bacteria derived from amylase on enzyme activity of the pine extracts haven’t been observed the inhibitory effect. Also disaccharides α-glycosidase enzyme that hydrolyzes on kindling of the pine was found to not have an inhibitory effect.

Protective Effect of Diosgenin on Streptozotocin Induced Diabetic Nephropathy in Experimental Rats

Diabetes mellitus is a multifactorial metabolic disorder associated with the diabetes related vascular diseases. Oxidative stress along with inflammation is the Key factor leading to diabetic complications. Present study was designed to investigate the protective role of diosgenin, a steroidal saponin, in diabetes induced early kidney injury and oxidative stress markers and histopathological changes in kidney of diabetic rats, induced by single intra-peritoneal injection of streptozotocin (55 mg/kg weight (b.w.). After 72 hrs, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for four weeks. At the end of the experiment, diabetic rats showed a significant increase in the levels of plasma glucose, glycosylated hemoglobin with a significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione, and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in kidney tissues of diabetic rats. Oral administration of diosgenin to diabetic rats considerably shrivelled the plasma glucose and exaggerated the endocrine level supported a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings recommend that diosgenin may have a helpful role against excretory organ harm evoked by aerobic stress within the diabetic state.

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.

Effect of Conjugated Blackcurrant Extract and Zinc Oxide Nanoparticles on Histopathologic Damage of Kidney Tissue in Diabetic Rats

Effect of Conjugated Blackcurrant Extract and Zinc Oxide Nanoparticles on Histopathologic Damage of Kidney Tissue in Diabetic Rats

Phytochemical Analysis and Antioxidant Property of Rhizome extracts aqueous of Phragmites australis in Alloxan Diabetic Rats

The present study was aimed to investigate the effect of phragmites australis aqueous extracts on lipid peroxidation and antioxidant status in some tissues of alloxan induced diabetic rats. In our experiment study, rats were divided into three groups of five animals in each; Control, diabetic and diabetic + 200 mg/kg extract plant groups. All rats except those in the control group were made diabetic using a single intraperitoneal injection of 150 mg/kg alloxan. Administration of extract began four days after induction of diabetes and lasted for three weeks. The results of the phytochemical analysis revealed that Total phenol and flavonoid content in P. Australis aqueous extract shows highest concentration in aqueous extract of P. australis (34.10mg GA EQ/gm, 3.27mg QEQ/gm). contained various bioactive compounds, including tanin, terpenoids, glycosides and flavonoids. Administration of (200mg/kg body weight/day) extracts in diabetic rats has remarkably improved the elevated levels of fasting blood glucose, triglyceride and LDL concentration. A significant decrease in lipid peroxidation (p<0.001) and small increase in the reduced glutathione (GSH) contents in kidney tissue of diabetic rats were observed. Our studies demonstrate the anti-hyperglycemic and anti-oxidative potential of phragmites australis, which could exert beneficial effects against the diabetes and associated free radicals complications in kidney tissue.

Modulation of Renal Insulin Signaling Pathway and Antioxidant Enzymes with Streptozotocin-Induced Diabetes: Effects of Resveratrol.

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rβ, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes’ gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

BIOCHEMICAL EVALUATION OF ANTIDIABETIC PROPERTIES OF SWERTIAMARIN, A SECOIRIDOID GLYCOSIDE OF ENICOSTEMMA LITTORALE LEAVES, STUDIED IN HIGH-FAT DIET–FED LOW-DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETIC RATS

Objective: Swertiamarin, a secoiridoid glycoside present in the leaves of Enicostemma littorale, is reported to be responsible for its pharmacological and beneficial properties. The present study was aimed to biochemically evaluate the antidiabetic properties of Swertiamarin in high fat diet fed - low dose streptozotocin (STZ)-treated diabetic rats.Methods: High-fat diet-fed low-dose STZ was used to induce experimental type 2 diabetes in rats. Diabetic rats were orally treated with swertiamarin (50 mg/kg b.w./rat/day) for 30 days. The physiological criterions such as food and fluid intake were recorded. Oral glucose tolerance test was performed. The levels of fasting blood glucose, plasma insulin, glycosylated hemoglobin A1c (HbA1c), hemoglobin, and homeostasis model assessment of insulin resistance (HOMA-IR) values were estimated. The activities of key enzymes involved in carbohydrate and glycogen metabolism in the liver and kidney tissues were assayed. The glycogen content in liver tissue was estimated.Result: Oral administration of swertiamarin to diabetic rats established a significant decline in the levels of fasting blood glucose, HbA1c as well as HOMA-IR values and an increase in plasma insulin and hemoglobin levels. The altered activities of key enzymes of carbohydrate and glycogen metabolism in liver and kidney tissues of diabetic rats were restored to near normalcy by swertiamarin treatment.Conclusion: Swertiamarin treatment maintains normoglycemia in diabetic rats by modulating the activities of key carbohydrate and glycogen metabolizing enzymes in the hepatic and renal tissues.

Garlic (Allium sativum) increases SIRT1 and SIRT2 gene expressions in the kidney and liver tissues of STZ- and STZ+niacinamide-induced diabetic rats.

Abstract Background Diabetic nephropathy and liver damage are important complications of diabetes mellitus (DM). Various factors, such as sirtuins (silent information regulators or SIRTs) are associated with these complications. Sirtuins are a family of NAD+-dependent proteins, and seven types of these can be found in mammalians. In this study, we evaluated the effects of aqueous garlic extract (G) on the expressions of SIRT1 and SIRT2 genes in the kidney and liver tissues of rats with types 1 and 2 diabetes. Methods A total of 36 male Wistar rats (230–280 g) were randomly divided into six groups: C: normal control rats, D1M: type 1 diabetic rats (induced with streptozotocin, STZ), D1M+G: type 1 diabetic rats that treated with garlic extract, D2M: type 2 diabetic rats (induced with STZ and niacinamide), D2M+G: type 2 diabetic rats treated with garlic extract, and G: normal rats that received garlic extract. At the end of the treatment time, kidney and liver tissue samples were collected from all rats. The SIRT1 and SIRT2 gene expressions were determined by qRT-PCR. Results The SIRT1 and SIRT2 gene expressions in the liver and kidney tissues of diabetic rats decreased significantly compared with those in the control rats (p&lt;0.05). After treatment with garlic extract, the gene expressions also increased significantly compared with those in the diabetic rats and are close to normal level (p&lt;0.05). Conclusions Garlic extract increased the SIRT1 and SIRT2 gene expressions in the livers and kidneys of diabetic rats. The antioxidant and anti-inflammatory effects of garlic have been proven in many studies. Thus, it is possible that garlic – with its effects on this pathway of gene expression – can have antioxidant and anti-inflammatory effects, thus decreasing diabetic complications.

Evaluation of the Antioxidant and Antiglycation Effects of Lactarius deterrimus and Castanea sativa Extracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats.

The present study aimed to investigate the beneficial effects of the treatment with extracts from the edible mushroom Lactarius deterrimus (Ld) and the chestnut Castanea sativa (Cs), separately and in combination (MIX Ld/Cs), on oxidative stress and advanced glycation end-product (AGE)-mediated hepatorenal injury in a rat model of streptozotocin (STZ)-induced diabetes by examining pathways responsible for maintenance of redox homeostasis. An experimental model of diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. The examined extracts were applied separately at a dose of 60 mg/kg i.p. and in combination (60 mg/kg each extract; i.p.) for 4 weeks, starting from the last day of STZ administration. The improvement of hepatorenal function in diabetic rats treated with the extracts was associated with an improved glycemic and lipid status and suppression of oxidative stress and thereby oxidative damage of lipids and DNA. Besides the fact that both extracts inhibited protein glycation and AGE formation in vitro, they also reduced non-enzymatic glycosylation in diabetic rats in vivo. The observed antiglycation activity of the examined extracts (separately and in combination) was accompanied with the inhibition of CML-mediated RAGE/NF-κB activation and reduction of enzymatic O-GlcNAcylation in liver and kidney tissues of diabetic rats. Taken together, these results reveal that the administration of chestnut and mushroom extracts, either individually or together, activates a coordinated cytoprotective response against diabetes-induced hepatorenal injury not only through recovery of the antioxidant defense system of the cell, but also through a marked antiglycation activity.

A new class of fast-response and highly selective fluorescent probes for visualizing peroxynitrite in live cells, subcellular organelles, and kidney tissue of diabetic rats

Peroxynitrite (ONOO(-)) is an extremely powerful oxidant in biological systems, and can react with a wide variety of molecular targets including proteins, lipids, and nucleic acids, eventually resulting in a series of disease states such as diabetes, Alzheimer's disease, cancer, arthritis, autoimmune, and other disorders. In this work, we present a new class of ONOO(-) fluorescent probes by exploiting the ONOO(-)-triggered N-oxidation and N-nitrosation reactions of aromatic tertiary amine for the first time. The as-obtained fluorescent probe A2 could detect ONOO(-) with quite fast fluorescence off-on response (within seconds), ultrasensitivity (detection limit: <2nM), and excellent selectivity over a series of biologically relevant reactive oxygen species as well as metal cations. With the probe, the endogenous ONOO(-) in activated RAW264.7 murine macrophage, EA.hy926 endothelial cells after oxygen glucose deprivation and reoxygenation (OGD/RO), and kidney tissue of diabetic rats has been successfully visualized. Based on the molecular platform of A2, we further develop its mitochondria- and lysosome-targetable fluorescent probes Mito-A2 and Lyso-A2 by installing the corresponding targeting groups to alkoxy unit of A2, and confirm their abilities to image ONOO(-) in mitochondria and lysosomes, respectively, by co-localization assays. It is greatly expected that these probes can serve as useful imaging tools for clarifying the distribution and pathophysiological functions of ONOO(-) in cells, subcellular organelles, and animal tissues.

Antidiabetic assessment; in vivo study of gold and core-shell silver-gold nanoparticles on streptozotocin-induced diabetic rats.

Recently, we have published a pioneering work on green biosynthesis and complete characterization of gold and core shell silver-gold nanoparticles (AuNPs and Ag@AuNPs). Herein, the so obtained nanoparticles are assessed for their antidiabetic activity in streptozotocin-induced diabetic rats. Thus, sixty-four male albino rats were divided into eight groups: control untreated; diabetic rats; diabetic rats received standard drug; diabetic rats received carrier only; diabetic rats received 0.5ml AuNPs; diabetic rats received 1ml AuNPs; diabetic rats received 0.5ml Ag@AuNPs and diabetic rats received 1ml Ag@AuNPs for twenty-one days. Results revealed that diabetic rats treated with AuNPs or Ag@AuNPs restored normal glucose level. In particular, Ag@AuNPs was found to significantly induce a reduction in blood glucose and restore both the high serum insulin level and glucokinase activity compared to the control normal rats. The results obtained disclose the effectual role of Ag@AuNPs in reducing the lipid profile, an anti-inflammatory effect in diabetic rats assessed using inflammatory markers IL-α and C-reactive protein (CRP). Histopathological examination of diabetic rats signifies distortion in the arrangement of cells around the central vein, inflammatory cells, pyknotic and apoptotic nuclei. Kidney of diabetic rat appears with vacuolation and pyknotic nuclei of some tubules. On the other hand, the liver of diabetic rat treated with Ag@AuNPs displayed normal hepatic cells with only few necrosis of hepatocytes. Ag@AuNPs restored the increased number of caspase-3 stained cells in the liver and kidney tissue in diabetic rats. In conclusion, Ag@AuNPs was observed to improve diabetic condition by limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats which subsequently evoke the potential impact of AuNPs as a cost effective therapeutic cure in diabetic treatments and its complications.

The correlation between oxidized low density lipoprotein receptor CD36 and renal tubular injury in diabetic rats

Objective To observe the expressions of oxidized low density lipoprotein(OxLDL)receptor CD36 in kidney tissue of diabetic rats and in tubular cells incubated with OxLDL, and to explore the association of CD36 with the tubular injury and renal fibrosis in the process of diabetic nephropathy. Methods Diabetic rat model with hyperlipidemia was established by feeding with high sugar and fat diet and injection of low dose streptozotocin intraperitoneally. The expression of CD36 in kidney tissues was analyzed immunohistochemically. Meanwhile, the tubular sclerosis and fibrosis injury index were estimated and calculated. NRK-52E cells were stimulated with 50 mg/L OxLDL for 5, 10, 24, and 48 h, or 100 and 150 mg/L OxLDLs for 2 and 3 days. The protein expression of CD36 was detected by Western blot. Results The expression of CD36 in the renal tubulointerstitium of diabetic rats was increased comparing to that in control rats, and was localized mainly at tubular region. The renal tubular damage index(STI)of diabetes group was higher than that in control group(5.54±1.5 vs 0.65±0.15, P<0.05). OxLDL stimulated CD36 expression in NRK-52E cells in a dose- and time-dependent manner. Conclusion The expression of CD36 was increased in renal tubular of diabetic rats, in consistent with STI. OxLDL increased CD36 expression in NRK-52E cells. These results suggest that the expression of CD36 is associated with renal tubular damages in experimental rat diabetes. (Chin J Endocrinol Metab, 2016, 32: 602-606) Key words: Diabetic nephropathy; Renal tubule; Oxidized low density lipoprotein; CD36

MicroRNA-146a and Metabolic Disorder

MicroRNA-146a is one of the inflammation related microRNAs that constitutes an imperative part in the immune system. The present study was designed to evaluate whether microRNA-146a and its effect on the expression of target proteins (TRAF6 and IRAK1) are involved in metabolic disorders such as type II diabetes. In the current study, we investigated the expression levels of microRNA-146a in kidneys of twenty diabetic rats. The results showed a four-fold increase in microRNA-146a level in the kidneys of diabetic rats which was associated with a significant reduction in the expression of IRAK1with no changes in TRAF6 expression levels. On the contrary, significant increase in NF-ᴋB, TNFα, and IL6 and IL1β concentrations in kidney tissues of diabetic rats was observed. In conclusion, MicroRNA-146a can be used as a marker in case of diabetes.