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

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.

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Shiqiang Wang

Objective To investigate the effects of exercise on the myocardial oxidative stress injury of diabetic rats, and discussed the role of Keap1/Nrf2 signaling pathway in this process Methods  Tyep 2 diabetic rat model was established by streptozotocin injection through abdominal cavity and high fat diet. The all the diabetic rats were divided into three groups: control group (NC), diabetes group(T2DM) and diabetes exercise group, NC and T2DM group were kept quiet for 8 weeks, T2DME group was trained for 8 weeks. After the exercise, weight, heart weight and blood were measured. MDA, T-SOD and GSH-PX enzyme were measured by biochemical method. Ho-1, Keap1, Nrf2 gene and protein expression were detected by RT-PCR and WesternBlotting. Results Compared with NC group, the weight of rats in the T2DM group significantly decreased [(528+/-71g vs 362+/-33g), P<0.05], HWI  significantly increased [(2.845+/-0.22 vs 3.841+/-0.21, P <0.05], blood glucose was significantly increased [(6.4±3.8 vs 26±7.5mmol/L), P <0.01],T-SOD and GSH-PX activity decreased significantly (P<0.05), Ho-1 protein expression increased (P<0.01), Keap1 and Nrf2 showed no significant changes, and Nrf2 nuclear transposition decreased (P<0.05). Compared with the T2DM group, no significant change in body weight and heart weight in the T2DME group, with significant decrease in HWI[(3.841±0.21 vs 3.235±0.23),P<0.05], with significant decrease in blood glucose [(26.0±7.5 vs 21.0±6.8),P<0.05]. Ho-1 gene and protein expression increased significantly(P<0.05and P<0.01), with no significant change of Keap1, while Nrf2 expression increased significantly (P < 0.05), and Nrf2 nuclear transposition increased significantly (P < 0.01). Conclusions Exercise activates the myocardial Keap1/Nrf2 signaling pathway in rats, promotes the expression of downstream antioxidant enzymes, increases cardiac antioxidant capacity, and resists diabetic myocardial oxidative stress injury.


Author(s):  
Rafighe Ghiasi ◽  
Roya Naderi ◽  
Roghayeh Sheervalilou ◽  
Mohammad Reza Alipour

Abstract Background Sirtuin1 is a regulator of oxidative stress involved in the management of diabetes complications. Due to the beneficial effects of swimming training in diabetes, this study aimed to investigate the effects of swimming training on pancreatic Sirtuin1, oxidative stress and metabolic parameters in type 2 diabetic male rats. Materials and methods Twenty-eight male Wistar rats (200–250 g) were randomly divided into four groups: control, diabetic, swim trained and swim trained diabetic rats (n = 7). Diabetes was induced by a high-fat diet and streptozotocin injection [35/kg intraperitoneally]. After 72 hours, animals with blood glucose levels ≥300 mg/dL were considered diabetic. Seven days after the induction of diabetes, animals in the exercise groups were subjected to swimming training (60 min/daily, 5 days/week) for 12 weeks. At the end of the intervention, the animals were anesthetized, and tissue/blood samples were prepared for measurements of metabolic parameters, albumin, the Sitruin1 gene and its protein expression levels, oxidative stress and histological study. Results This study indicated that the diabetic rats had a significant decrease (p < 0.01, p < 0.05) in pancreatic Sitruin1 gene and its protein expression levels, antioxidant enzymes, serum albumin, and the quantitative insulin sensitivity check index, but a significant increase (p < 0.01) in malondialdehyde level. Swimming training resulted in a considerable improvement (p < 0.01, p < 0.05) in pancreatic Sitruin1 gene and its protein expression levels, antioxidant enzymes, serum levels of albumin and metabolic parameters. In addition, histological findings indicated the beta-cells conservation. Conclusions This study suggested that pancreatic Sitruin1 may be a promising therapeutic target for diabetic complications.


Author(s):  
Shahin Kashefimehr ◽  
Mohammadreza Nasirzadeh

Introdution: Diabetes is the most common endocrine disorder characterized by hyperglycemia. Increasing the oxidative stress and changing the amount of antioxidants play important roles in pathogenesis of diabetes. Nowadays to control diabetes and its complications, the use of herbal drugs is considered widely. In this study, we investigated the effect of oleuropein on antioxidant enzymes activity of heart tissue in Streptozotocin induced diabetic male rats. Methods: In this study, 30 adult male Wistar rats with a weight range of 190±30 gr were randomly divided into 3 groups(n=10 in each group): 1) control group or intact rats, 2) diabetic rats, and 3) treatment group, which received 60 mg/kg oleuropein for 30 days by gastric gavage. Diabetes was induced by injection of streptozotocin (60 mg/kg) intraperitoneally. At the end of the treatment, serum concentrations of blood glucose and heart tissue antioxidant enzymes activity were determined. The obtained data were analyzed using  SPSS Inc., Chicago, IL; Version 18, statistical method of one way variance analysis and post hoc-Duncan test . Results: The results showed that serum concentration of glucose decrease significantly in treatment group compared with the diabetic group (p=0.000). Also, TAC, SOD and GPX activity increased significantly in the treatment group compared with the diabetic group (p=0.000). Conclusion: This study showed that oleuropein can prevent blood glucose increasing and reinforce antioxidant system of cardiac tissue in diabetic rats.


2021 ◽  
Vol 44 (1) ◽  
pp. 94-104
Author(s):  
Fawziah A. Al-Salmi ◽  
Reham Z. Hamza

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO4) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin resistance, and hyperglycemia were assessed. Fifty male albino rats were divided into five groups, and all treatments were administrated at 9:00 a.m. daily for 60 successive days: control, STZ (Streptozotocin; 50 mg/kg of STZ was given to 6 h fasted animals in a single dose, followed by confirmation of diabetic state occurrence after 72 h by blood glucose estimation at >280 mg/dl), STZ (Diabetic) plus administration of VOSO4 (15 mg/kg) for 60 days, STZ (Diabetic) plus administration of selenium tetrachloride (0.87 mg/Kg), and STZ plus VOSO4 and, after 1/2 h, administration of selenium tetrachloride at the above doses. The test subjects’ blood glucose, insulin hormone, HbA1C, C-peptide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, myeloperoxidase, and xanthine oxidase), markers of lipid peroxidation (MDA), and histological sections of pancreatic tissues were evaluated, and a comet assay was performed. Histological sections in pancreas tissues were treated as indicators of both VOSO4 and selenium tetrachloride efficacy, either alone or combined, for the alleviation of STZ toxicity. The genotoxicity of diabetes mellitus was assessed, and the possible therapeutic roles of VOSO4 or selenium tetrachloride, or both, on antioxidant enzymes were studied. The findings show that the administration of VOSO4 with selenium tetrachloride reduced oxidative stress to normal levels, lowered blood glucose levels, and elevated insulin hormone. Additionally, VOSO4 with selenium tetrachloride had a synergistic effect and significantly decreased pancreatic genotoxicity. The data clearly show that both VOSO4 and selenium tetrachloride inhibit pancreatic and DNA injury and improve the oxidative state in male rats, suggesting that the use of VOSO4 with selenium tetrachloride is a promising synergistic potential ameliorative agent in the diabetic animal model.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 317
Author(s):  
Saleh A. Almatroodi ◽  
Abdullah M. Alnuqaydan ◽  
Ali Yousif Babiker ◽  
Mashael Abdullah Almogbel ◽  
Amjad Ali Khan ◽  
...  

The aim of present study is to investigate the role of 6-gingerol in ameliorating the renal injury in streptozotocin (STZ)-induced diabetic rats. The diabetes was induced by using a single dose of freshly prepared STZ (55 mg/kg body weight) intraperitoneally which causes the degeneration of pancreatic Langerhans islet β-cells. The diabetic rats were treated with oral gavage of 6-gingerol (10 mg/kg b.w.). The treatment plan was continued for 8 weeks successively and the body weight and fasting blood glucose levels were weekly checked. The biochemical parameters like lipid profile, kidney profile, antioxidant enzyme levels, lipid peroxidation and anti-inflammatory marker levels were investigated after the treatment plant. The pathological condition of kidneys was examined by haematoxylin-eosin (H&E) staining besides this analysis of NF-κB protein expression by immuno-histochemistry was performed. Some of the major parameters in diabetes control vs. normal control were reported as fasting blood glucose (234 ± 10 vs. 102 ± 8 mg/dL), serum creatinine (109.7 ± 7.2 vs. 78.9 ± 4.5 μmol/L) and urea (39.9 ± 1.8 vs. 18.6 mg/dL), lipid profile levels were significantly enhanced in diabetic rats. Moreover, diabetic rats were marked with decreased antioxidant enzyme levels and increased inflammatory markers. Treatment with 6-gingerol significantly restored the fasting blood glucose level, hyperlipidaemia, Malondialdehyde (MDA) and inflammatory marker levels, NF-κB protein expression and augmented the antioxidant enzyme levels in the kidneys of diabetic rats. The kidney damage was significantly normalized by the treatment of 6-gingerol and it provides an evidence that this novel compound plays a significant role in the protection of kidney damage. These findings demonstrate that 6-gingerol reduces lipid parameters, inflammation and oxidative stress in diabetic rats, thereby inhibiting the renal damage. Our results demonstrate that use of 6-gingerol could be a novel therapeutic approach to prevent the kidney damage associated with the diabetes mellitus.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
A. M. Adeosun ◽  
F. O. Asejeje ◽  
O. M. Ighodaro ◽  
B. A. Oluwole ◽  
O. A. Akinloye

Abstract Background Diabetes mellitus is clinically underlined by hyperglycemia and dyslipidemia. In view of this, the current study assessed the glycemic and lipidemic control potentials of methanol extract of Sruchium sparganophora leaves (SPA) in the alloxan-induced diabetic model using male Wistar rats. Experimental diabetes was induced through a single intraperitoneal injection of 120 mg/kg freshly prepared alloxan. Thirty-six rats were randomly assigned into six groups of normoglycemic control, untreated diabetic group, and diabetic treated with (i) metformin (12 mg), (ii) metformin 12 mg + SPA 300 mg/kg, (iii) SPA 300 mg/kg, and (iv) SPA 600 mg/kg per os twice at 9.00 and 18.00 h daily for 10 days. Fasting blood glucose (FBG) level and markers of dyslipidemia, and oxidative stress markers were determined. Results SPA at selected doses decreased fasting blood glucose which was significantly (p < 0.05) raised by alloxan. Increase in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations and decrease in HDL-cholesterol (HDL-C) concentration (p < 0.05) caused by alloxan were significantly moderated by SPA at selected doses. Glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities reduced by alloxan (p < 0.05) in both the liver and pancreas were reversed by SPA 300 and 600, and its combination with metformin. Decreased reduced glutathione (GSH) concentration in alloxan diabetic rats was also reversed by the extract, while the level of malondialdehyde (MDA) exacerbated by alloxan (p < 0.05) in the tissues was decreased by the extracts. Conclusion Struchium sparganophora possesses considerable antihyperglycemic, antidyslipidemic, and antioxidant potentials without compromising organ functionality.


2009 ◽  
Vol 11 (4) ◽  
pp. 271-276 ◽  
Author(s):  
Craig B. Webb ◽  
Lauren Falkowski

This study was undertaken to test the hypothesis that oxidative stress is increased and neutrophil function is decreased in cats with diabetes mellitus (DM). Measures of oxidative stress and neutrophil function were evaluated in 20 control and 15 diabetic cats. Cats were then fed a diet designed specifically for feline diabetics (Purina DM Dietetic Management Feline Formula) for 8 weeks, after which all assays were repeated. Cats with DM had significantly less plasma superoxide dismutase (SOD) than control cats, consistent with a greater degree of oxidative stress in the DM group. Following 8 weeks of consuming a diabetes-specific diet glutathione peroxidase, an antioxidant enzyme increased significantly in both groups. Other parameters of oxidative stress, as well as neutrophil function, were similar between groups and did not change following dietary intervention. The DM cats were significantly older and heavier than the control cats, which may have contributed to differences in parameters of oxidative stress and levels of antioxidant enzymes between these groups, but the decreased level of SOD enzyme in the diabetic group would appear to support the continued development of targeted antioxidant supplementation for this cats with this disease.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Naseer Ali Shah ◽  
Muhammad Rashid Khan

Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) ofSida cordatawas investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role ofS. cordatawas investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
S. A. Sheweita ◽  
S. Mashaly ◽  
A. A. Newairy ◽  
H. M. Abdou ◽  
S. M. Eweda

Alhagi maurorum(camel thorn plant) is a promising medicinal plant due to the presence of flavonoids and phenolic compounds as major contents of its constituents. No previous study has been conducted before onA. maurorum extractsas an antioxidative stress and/or antidiabetic herb in STZ-induced DM in rats. Therefore, four groups of rats were allocated as control (C), STZ-induced DM (D), and STZ-induced DM supplemented with 300 mg/kg BW of either aqueous extract (WE) or ethanolic extract (EE) ofA. maurorum. The plasma levels of glucose, TG, TC, LDL-C and VLDL-C, MDA, and bilirubin and the activities of transaminases and GR were significantly increased in the diabetic group. Also, diabetic rats showed severe glucose intolerance and histopathological changes in their livers. In addition, levels of insulin, total proteins, GSH, and HDL-C and the activities of SOD, GPx, and GST were significantly decreased in the diabetic rats compared to those of the control group. The ingestion ofA. maurorumextracts lowered the blood glucose levels during the OGTT compared to the diabetic rats and restored all tested parameters to their normal levels with the exception of insulin level that could not be restored. It is concluded thatA. maurorumextracts decreased elevated blood glucose levels and hyperlipidemia and suppressed oxidative stress caused by diabetes mellitus in rats.


2020 ◽  
Vol 17 (6) ◽  
pp. 147916412096699
Author(s):  
Wenru Li ◽  
Chaonan Zhu ◽  
Tianheng Liu ◽  
Weifang Zhang ◽  
Xu Liu ◽  
...  

Aims: The objective of this study was to explore the effects of epigallocatechin-3-gallate (EGCG) on type 2 diabetes mellitus (T2DM). Main methods: Male Sprague–Dawley rats were allocated into six groups. The control group received a conventional diet. The diabetic group received a high-sucrose high-fat (HSHF) diet for 4 weeks and then was fasted and injected with streptozotocin (STZ); subsequently, the rats received a HSHF diet for another 4 weeks to develop diabetes. The four treatment groups were diabetic rats that received intragastric metformin (500 mg/kg/day) or EGCG (25, 50, and 100 mg/kg/day) for 10 weeks. All groups except the control group received a HSHF diet throughout the experiment. Several biochemical parameters such as fasting blood glucose (FBG), postprandial blood glucose (PBG), liver glycogen, muscle glycogen, fasting serum insulin (FSI), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess the effects of EGCG on glycemic control, insulin resistance, lipid profile, and oxidative stress. Furthermore, oxidative stress in pancreatic islet β cells was detected by dihydroethidium staining. Key findings: A HSHF diet and STZ injection induced T2DM, as indicated by changed blood glucose and body weight, which was accompanied by insulin resistance, an altered lipid profile, and oxidative stress. Interestingly, EGCG treatment dose-dependently recovered these indexes. Significance: EGCG successfully ameliorated glycemic control and insulin sensitivity while reducing the lipid profile and oxidative stress in a T2DM rat model.


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