Effect of paricalcitol on pancreatic oxidative stress, inflammatory markers, and glycemic status in diabetic rats

2017 ◽  
Vol 187 (1) ◽  
pp. 75-84 ◽  
Author(s):  
T. M. Ali ◽  
B. El Esawy ◽  
A. Elaskary
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Markers ◽  
Diabetic Rats ◽  
Glycemic Status

scholarly journals Thymoquinone, the Most Prominent Constituent of Nigella Sativa, Attenuates Liver Damage in Streptozotocin-Induced Diabetic Rats via Regulation of Oxidative Stress, Inflammation and Cyclooxygenase-2 Protein Expression

2021 ◽  
Vol 11 (7) ◽  
pp. 3223
Author(s):  
Saleh A. Almatroodi ◽  
Abdullah M. Alnuqaydan ◽  
Mohammed A. Alsahli ◽  
Amjad Ali Khan ◽  
Arshad Husain Rahmani
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Enzymes ◽  
Blood Glucose ◽  
Liver Function ◽  
Protein Expression ◽  
Inflammatory Markers ◽  
Density Lipoprotein ◽  
Diabetic Rats

Diabetes mellitus (DM) is a multifaceted metabolic disorder that results in dysfunction and failure of various organs. The present study aimed to evaluate the role of Thymoquinone (TQ), on antidiabetic, oxidative stress, and anti-inflammatory activities in streptozotocin (STZ)-induced (55 mg/kg b.w) diabetic rats. TQ was orally given for 8 consecutive weeks at dose of 150 mg/kg b.w. The blood glucose, insulin, total cholesterol, triglycerides, liver function enzymes, high density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol levels were measured accordingly in control, diabetes control (DC), and TQ-treatment groups. These experiments confirmed that TQ conserves the insulin level (0.4 ng/mL vs. 0.23 ng/mL), fasting blood glucose (146 ± 7 mg/dL vs. 225 ± 5 mg/dL), and HbA1c (7.5% vs. 10.6%) quite considerably as compared to DC animals. Our results also confirmed that TQ treatment conserves the body weight and lipid profile significantly in STZ-treated animals as compared to the DC group. Moreover, the antioxidant enzymes (GSH, SOD, GST, and CAT) levels decreased, liver function enzymes (ALT, AST, and ALP), lipid peroxidation and inflammatory markers (TNF-α, CRP, IL-1β, IL-6) increased by STZ treatment, that is significantly restored after TQ treatment. As compared to untreated animals, TQ restored the hepatocytes architectural changes and collagen fibers and cox-2 protein expression in liver tissues as evaluated by hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry staining. Taken together, all these findings indicated that TQ ameliorates glucose level and lipid metabolism. It restores liver function, antioxidant enzymes, anti-inflammatory markers, and maintains hepatocytes architecture in STZ-induced diabetes mellitus rats. Here, in this study, we have demonstrated for the first time the role of TQ in the reduction of the expression of cyclooxygenase-2 and fibrosis formation in diabetic rats. Based on the findings, the study suggests that TQ is a novel natural drug with a wide range of clinical applications including the management of diabetes mellitus.

scholarly journals LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9196 ◽  
Author(s):  
Mohamed Mohany ◽  
Ahmed Z. Alanazi ◽  
Faleh Alqahtani ◽  
Osamah M. Belali ◽  
Mohammed M. Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Markers ◽  
Time Course ◽  
Therapeutic Potential ◽  
Microvascular Complications ◽  
Substantial Reduction ◽  
Diabetic Rats ◽  
Tissue Homogenate ◽  
Oxidative Stress Biomarkers ◽  
Tnf Α

Background Diabetic nephropathy (DN) is among the most common microvascular complications of diabetes resulting in end-stage renal disease and therefore search for candidates which can ameliorate the kidney function is needed simultaneously with standard diabetic pharmacotherapy. The current study was aimed to investigate the effect of long term sacubitril/valsartan therapy (LCZ696) in diabetic rats to assess its ameliorative impact against various pathological parameters such as oxidative stress, inflammation and glomerulosclerosis associated with chronic DN. Methods A single dose (60 mg/kg/day) of STZ was used to induce type 1 diabetes in adult male wistar rats. 2 weeks after diabetes induction, these rats were treated orally with valsartan (31 mg/kg) or LCZ696 (68 mg/kg) for 6 weeks. At end of the treatment period, serum and kidney samples were collected and analyzed. The serum levels of glucose, insulin, urea, creatinine, TNF-α, IL-1β, IL-6 and IL-10 levels were estimated. In renal tissue homogenate, the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB along with oxidative stress biomarkers including thiobarbituric acid-reacting substances (TBARs), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) were assessed. Histological changes were observed in kidney. Results Time course therapy withLCZ696 and valsartan in diabetic rats resulted in significant reduction of serum glucose, urea and creatinine levels (P < 0.05). Additionally, serum of treated diabetic rats showed a diminution in inflammatory (TNF-α, IL-1β, IL-6) and increment in anti-inflammatory (IL-10) cytokines levels (P < 0.05). Tissue homogenate of the kidney extracted from LCZ696 and valsartan treated diabetic rats revealed a substantial reduction in the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB and sufficient restoration of anti-oxidant enzyme levels (P < 0.05). Finally, in the histological sections of the kidney, prevention of renal injury was observed with limited necrosis and inflammatory cells infiltration. Conclusion Present data suggest that LCZ696 has sufficient therapeutic potential to restrict DN progression through inhibiting inflammation, oxidative stress and glomerulosclerosis.

ApoE-Derived Peptides Attenuated Diabetes-Induced Oxidative Stress and Inflammation

2020 ◽  
Vol 27 (3) ◽  
pp. 193-200
Author(s):  
Sunil A. Nankar ◽  
Yogesh Bulani ◽  
Shyam S. Sharma ◽  
Abhay H. Pande
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Markers ◽  
Total Body Weight ◽  
Diabetic Rats ◽  
Potential Candidate ◽  
Human Apolipoprotein ◽  
Cellular Assays ◽  
Inflammatory Conditions ◽  
Oxidative Effects ◽  
And Oxidative Stress

Background: Peptides derived from the apolipoproteins (apo-mimetic peptides) have emerged as a potential candidate for the treatment of various inflammatory conditions. Our previous results have shown that peptides derived from human apolipoprotein-E interact with various pro-inflammatory lipids and inhibit their inflammatory functions in cellular assays. Objective: In this study, two apoE-derived peptides were selected to investigate their antiinflammatory and anti-oxidative effects in streptozotocin-induced diabetic model of inflammation and oxidative stress. Methods: The peptides were injected intraperitoneally into the streptozotocin-induced diabetic rats and their anti-inflammatory and anti-oxidative effects were evaluated by monitoring various oxidative and inflammatory markers. Results: Administration of 4F, E5 and E8 peptides decreased the oxidative and inflammatory markers in STZ-induced diabetic rats to different extent, while had no significant effect on the other diabetic parameters (viz. total body weight of animals and increased blood glucose level). E5 peptide was found to be relatively more effective than 4F and E8 peptides in decreasing inflammation and oxidative stress. Conclusion: E5 peptide can be developed as a potential candidate for inflammatory conditions.

scholarly journals Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yachun Li ◽  
Shuai Guo ◽  
Fan Yang ◽  
Lifei Liu ◽  
Zhiqiang Chen
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Total Protein ◽  
Inflammatory Markers ◽  
Underlying Mechanism ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Nrf2 Signaling Pathway

Diabetic nephropathy (DN), a severe microvascular complication of diabetes, is one of the leading causes of end-stage renal disease. Huayu Tongluo Recipe (HTR) has been widely used in the clinical treatment of DN in China, and its efficacy is reliable. This study aimed to explore the renoprotective effect of HTR and the underlying mechanism. Male Sprague-Dawley rats were fed with high sugar and fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. Rats in each group were respectively given drinking water, HTR, and irbesartan by gavage for 16 weeks. 24-hour urine samples were collected every 4 weeks to detect the content of total protein and 8-OHdG. Blood samples were taken to detect biochemical indicators and inflammatory markers at the end of 16th week. Renal tissue was collected to investigate pathological changes and to detect oxidative stress and inflammatory markers. AMPK/Nrf2 signaling pathway and fibrosis-related proteins were detected by immunohistochemistry, immunofluorescence, real-time PCR, and western blot. 24h urine total protein (24h UTP), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), and triglyceride (TG) were decreased in the rats treated with HTR, while there was no noticeable change of blood glucose. HTR administration decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in kidneys, complying with reduced 8-OHdG in the urine. The levels of TNF-α, IL-1β, and MCP1 and the expression of nuclear NFκB were also lower after HTR treatment. Furthermore, HTR alleviated pathological renal injury and reduced the accumulation of extracellular matrix (ECM). Besides, HTR enhanced the AMPK/Nrf2 signaling and increased the expression of HO-1 while it inhibited the Nox4/TGF-β1 signaling in the kidneys of STZ-induced diabetic rats. HTR can inhibit renal oxidative stress and inflammation to reduce ECM accumulation and protect the kidney through activating the AMPK/Nrf2 signaling pathway in DN.

Attenuation of oxidative stress in hepatic and pancreatic tissues of STZ-induced diabetic rats treated with aqueous extract of Vochysia rufa

Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
NM De Gouveia ◽  
IB Moraes ◽  
RMF Sousa ◽  
MB Neto ◽  
AV Mundim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aqueous Extract ◽  
Diabetic Rats

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Stevia Rebaudiana ◽  
Diabetic Rats ◽  
Control Group ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

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