scholarly journals P0991EFFECTS OF TRIGONELLA FOENUM GRAECUM AND SODIUM ORTHOVANADATE ON ALTERED RENAL MEMBRANE FUNCTIONS IN ALLOXAN DIABETIC RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pardeep Kumar ◽  
Najma Baquer
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Glucose Transporter ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sodium Orthovanadate ◽  
High Blood Glucose ◽  
Trigonella Foenum Graecum

Abstract Background and Aims The present study was carried out to observe, the antihyperglycemic and renoprotective effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose, renal functions, expression of glucose transporter, DNA fragmentation, inflammatory cytokines and oxidative stress markers in kidney tissues and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Method Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight.) and rats were treated with 2 IU insulin, 0.6mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Renal damage was assessed by measuring proteinuria, enzymuria, expression of glucose transporters, renin-angiotensin system, and activities of polyol pathway enzymes. Results Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activity of Na+K+ATPase decreased in diabetic kidney. Diabetic rats exhibited an increased level of lipid peroxidation, intracellular Ca2+ levels, and decreased membrane fluidity. Combined therapy of lower dose of SOV with TSP significantly reduced metabolites of polyol pathway, oxidative stress, nitric oxide, and N-acetyl-β-d-glucosaminidase activity with glucose transporter in kidney of alloxan diabetic rats. Markers of podocyte damage in kidney (nephrin, podocin, and podocalyxin) and their urinary excretion were normalized along with downregulation of the expression of kidney injury molecule-1 by SOV and TSP treatment. TSP treatment alone is partially effective in restoring the above diabetes induced alterations. Dietary combined SOV and TSP effectively countered the diabetes-induced structural abnormalities of renal tissue. Conclusion Our results showed that lower doses of SOV (0.2mg/ml) could be used in combination with TSP to effectively in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect and renoprotective actions.

scholarly journals Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats

2015 ◽  
Vol 116 (2) ◽  
pp. 122-138 ◽  
Author(s):  
Pardeep Kumar ◽  
Asia Taha ◽  
Nitin Kumar ◽  
Vinod Kumar ◽  
Najma Zaheer Baquer
Keyword(s):  
Lipid Peroxidation ◽  
Blood Glucose ◽  
Monoamine Oxidase ◽  
Combined Therapy ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Sodium Orthovanadate ◽  
Altered Level ◽  
High Blood Glucose ◽  
Trigonella Foenum Graecum

Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

scholarly journals Ameolirative effects of garlic (Allium sativum L.,) in streptozotocin induced oxidative stress in diabetic brain of rat

2020 ◽  
Vol 11 (4) ◽  
pp. 7950-7957
Author(s):  
Pratap Reddy K ◽  
Bhaskar Nagilla ◽  
Varija K
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Garlic Extract ◽  
Advanced Glycation ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glycation End Products ◽  
End Products

The aim of the present study was to evaluate the protective effect of methanol garlic extract on the enzymes related with polyol pathway, advanced glycation end products, markers of oxidative stress and antioxidant status in brain of streptozotocin induced diabetic rats. Antioxidant capability of methanol extract of garlic was evaluated by 2,2-diphenyl-2-picrylhydrazyl hydrate radical and FOX (ferrous ion oxidation-xylenol orange) H2O2 scavenging test. Diabetes was induced by single i.p injection of STZ (32mg/kg per body Wt.,). Blood glucose levels and body wt, were measured on every 7th day over a period of 30 days. The diabetic rats treated with garlic extract at two doses 250mg/kg and 500mg/kg body wt., by oral administration. Diabetic rats showed significant increase in food and water intake, decrease in blood glucose levels, body weights, but could not show any recovery by garlic treatment. Garlic treatment significantly decreased aldose reductase (AR); sorbitol dehydrogenase (SD) and glutathione S-transferase (GST) enzyme activities. A decrease of malndialdehyde (MDA), Protein carbonyls (PC), Pentosidine advance oxidation protein products (AOPP), Advanced glycation end products (AGEs) was also observed. Additionally garlic administration produced a restoration of brain superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) in diabetic rats. Garlic treatment also reduced the free radical formation and progression of hyperglycemia induced diabetic complications by decreasing influx of glucose into the polyol pathway and increased activity of antioxidant enzymes. The current study reveals exerts, efficiently, an attenuating effect of methanol garlic extract exterted antihyperlgycemic, antioxidant and anti-glycating effects in a dose dependent manner in diabetic rats.

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.

scholarly journals Hypoglycemic and antioxidative activities of ethanol seed extract of Hunteria umbellate (Hallier F.) on streptozotocin-induced diabetic rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olubanke O. Ogunlana ◽  
Babatunde O. Adetuyi ◽  
Miracle Rotimi ◽  
lohor Esalomi ◽  
Alaba Adeyemi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Seed Extract ◽  
The Body ◽  
High Concentration ◽  
Group 5

Abstract Background Diabetes, a global cause of mortality in developing countries is a chronic disorder affecting the metabolism of macromolecules and has been attributed to the defective production and action of insulin characterized by persistent hyperglycemic properties. This global disorder harms organs of the body such as the liver, kidney and spleen. Medicinal plants such as Hunteria umbellate have been shown to possess hypoglycemic, antioxidative and anti-diabetic properties owing to the high concentration of active phytochemical constituents like flavonoids and alkaloids. The present study seeks to evaluate the hypoglycemic activities of ethanolic seed extract of Hunteria umbellate on streptozotocin-induced diabetes rats. Methods Thirty (30) female experimental rats were randomly divided into five groups with six rats per group and were administered streptozotocin (STZ) and Hunteria umbellate as follows. Group 1 served as control and was given only distilled water, group 2 rats were administered 60 mg/kg STZ; Group 3 was administered 60 mg/kg STZ and 100 mg/kg metformin; group 4 rats were administered 60 mg/kg STZ and 800 mg/kg Hunteria umbellate, group 5 rats 60 mg/kg STZ and 400 mg/kg Hunteria umbellate. The fasting blood glucose level of each rat was measured before sacrifice. Rats were then sacrificed 24 h after the last dose of treatment. Results The results showed that Hunteria umbellate significantly reversed STZ-induced increase in fasting blood glucose and increase in body and organs weight of rats. Hunteria umbellate significantly reversed STZ-induced decrease in antioxidant enzyme in liver, kidney and spleen of rats. Hunteria umbellate significantly reversed STZ-induced increase in oxidative stress markers in liver, kidney and spleen of rats. Conclusion Collectively, our results provide convincing information that inhibition of oxidative stress and regulation of blood glucose level are major mechanisms through which Hunteria umbellate protects against streptozotocin-induced diabketes rats.

High Blood Glucose Levels Affect Auditory Brainstem Responses after Acoustic Overexposure in Rats

2021 ◽  
pp. 1-8
Author(s):  
Jae-Hun Lee ◽  
Sang Hee Ji ◽  
Jae Yun Jung ◽  
Min Young Lee ◽  
Chi-Kyou Lee
Keyword(s):  
Blood Glucose ◽  
Hearing Threshold ◽  
Auditory Brainstem ◽  
Diabetic Rats ◽  
Control Groups ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hearing Function ◽  
Brainstem Response

Introduction: Diabetes mellitus (DM) is a systemic disease characterized by hyperglycemia and several pathological changes. DM-related hearing dysfunctions are associated with histological changes. Here, we explore hearing function and synaptic changes in the inner hair cells (IHCs) of rats with streptozotocin (STZ)-induced diabetes. Methods: STZ was injected to trigger diabetes. Rats with DM were exposed to narrow-band noise (105 dB SPL) for 2 h, and hearing function was analyzed 1, 3, 7, and 14 days later. Both the hearing threshold and the peak 1 amplitude of the tone auditory brainstem response were assessed. After the last functional test, animals were sacrificed for histological evaluation. Results: We found no changes in the baseline hearing threshold; however, the peak 1 amplitude at the low frequency (4 kHz) was significantly higher in both DM groups than in the control groups. The hearing threshold had not fully recovered at 14 days after diabetic rats were exposed to noise. The peak 1 amplitude at the higher frequencies (16 and 32 kHz) was significantly larger in both DM groups than in the control groups. The histological analysis revealed that the long-term DM group had significantly more synapses in the 16 kHz region than the other groups. Conclusions: We found that high blood glucose levels increased peak 1 amplitudes without changing the hearing threshold. Diabetic rats were less resilient in threshold changes and were less vulnerable to peak 1 amplitude and synaptic damage than control animals.

Attenuation of erythrocyte membrane oxidative stress bySesbania grandiflorain streptozotocin-induced diabetic rats

2015 ◽  
Vol 93 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Chandrabose Sureka ◽  
Thiyagarajan Ramesh ◽  
Vavamohaideen Hazeena Begum
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Blood Glucose ◽  
Erythrocyte Membrane ◽  
Osmotic Fragility ◽  
Diabetic Rats ◽  
Glycosylated Haemoglobin ◽  
Albino Rats ◽  
Enzymatic Antioxidants ◽  
Protective Effects

The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190–220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.

Amelioration of oxidative stress by dietary fenugreek (Trigonella foenum-graecum L.) seeds is potentiated by onion (Allium cepa L.) in streptozotocin-induced diabetic rats

2017 ◽  
Vol 42 (8) ◽  
pp. 816-828 ◽  
Author(s):  
Seetur R. Pradeep ◽  
Krishnapura Srinivasan
Keyword(s):  
Oxidative Stress ◽  
Beneficial Effect ◽  
Allium Cepa ◽  
Diabetic Rats ◽  
Dietary Interventions ◽  
Fenugreek Seeds ◽  
Soluble Fibre ◽  
Trigonella Foenum Graecum ◽  
Allium Cepa L ◽  
Trigonella Foenum Graecum L

Oxidative stress has a crucial role in the progression of diabetes and its complications. Soluble fibre-rich fenugreek seeds (Trigonella foenum-graecum L.) are understood to have a beneficial effect in the management of diabetes. Previously, we have shown that the amelioration of diabetic hyperglycemia and related metabolic abnormalities was potentiated by onion (Allium cepa L.) in experimental rats. The present study evaluated the additive beneficial effect of dietary fenugreek seeds (10%) and onion (3%) on oxidative stress in diabetic rats. These dietary interventions lowered oxidative stress, the combination producing a higher beneficial effect (p < 0.05), although not additive. Dietary fenugreek, onion, or fenugreek+onion countered hypercholesterolemia (p < 0.05), especially from low-density lipoprotein−associated fraction by 43%, 35%, and 54%, respectively. Elevated concentrations of cholesterol and triglycerides in the liver and heart under diabetic conditions were significantly counteracted by these dietary interventions, with the additive combination resulting in greater effect. These findings were also corroborated by restoration of histopathological abnormalities of heart and liver tissues along with lowered heart and liver weights. It is inferred that an alleviation of oxidative stress contributes further to the antidiabetic influence and this nutraceutical potential of fenugreek seeds and onion was higher when consumed together.

scholarly journals PO-086 Exercise enhances cardiac antioxidant capacity in diabetic rats through the Keap1/Nrf2 signaling pathway

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Shiqiang Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Stress Injury ◽  
Myocardial Oxidative Stress ◽  
Nrf2 Signaling Pathway ◽  
Gene And Protein Expression

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.

Galectin-3 mediates high-glucose-induced cardiomyocyte injury by the NADPH oxidase/reactive oxygen species pathway

2020 ◽  
Vol 98 (11) ◽  
pp. 826-833
Author(s):  
Jingang Sun ◽  
Lijuan Zhang ◽  
Jianhai Fang ◽  
Shuguo Yang ◽  
Lianghua Chen
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Nadph Oxidase ◽  
Blood Glucose Level ◽  
Body Mass ◽  
Glucose Level ◽  
High Glucose ◽  
Cardiac Injury ◽  
High Blood Glucose ◽  
Galectin 3

Galectin-3 is a member of the β-galactoside-binding lectin family taking part in the regulation of inflammation, angiogenesis, and fibrosis. This study was designed to study the improved effect of galectin-3 inhibition on diabetic cardiomyopathy (DCM). Sprague–Dawley rats were randomized into the control, DCM, and DCM + modified citrus pectin (MCP) (a galectin–3 pharmacological inhibitor) groups. After 8 weeks, streptozotocin-induced DCM led to high blood glucose level, oxidative stress, cardiac injury, and dysfunction accompanied by suppressed body mass. On the contrary, MCP (100 mg·kg−1·day−1) administration improved body mass and blood glucose level and attenuated cardiac injury and dysfunction in DCM rats. Additionally, MCP attenuated pathological changes in plasma and myocardial tissue markers of oxidative stress, such as hydrogen peroxide and malonyldialdehyde, although it did not change superoxide dismutase activities, which were decreased in the DCM group. The levels of oxidative stress associated proteins evaluated by Western blot, such as p67phox and NADPH oxidase 4, were obviously increased in the DCM group, while they were reversed by MCP treatment. Therefore, galectin-3-mediated high-glucose-induced cardiomyocyte injury and galectin-3 inhibition attenuated DCM by suppressing NADPH oxidase. These findings suggested that galectin-3 could be a potential target for treatment of patients with DCM.

scholarly journals Spirulina maxima and its effect on antioxidant activity in fructose induced oxidative stress with histopathological observations

2015 ◽  
Vol 62 (2) ◽  
pp. 13-19
Author(s):  
Urmila Jarouliya ◽  
Anish Zacharia ◽  
Raj K. Keservani ◽  
Godavarthi B.K.S Prasad
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Superoxide Dismutase ◽  
Blood Glucose ◽  
Reduced Glutathione ◽  
Thiobarbituric Acid ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Thiobarbituric Acid Reactive Substances ◽  
Spirulina Maxima

Abstract Diabetes mellitus is a metabolic disorder characterised by hyperglycemia and oxidative stress. The aim of the present study is to explore the antioxidant effect of Spirulina maxima in rat model along with the histopathological observations. Diabetes was induced by feeding 10% fructose solution orally to Wistar rats (n = 6) for 30 days, analysed for plasma blood glucose and the markers of the oxidative stress [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)]. These biochemical studies were associated with histopathological examination of liver and kidney sections. The microalga Spirulina maxima being rich in proteins and other essential nutrients is widely used as a food supplement. S. maxima at a dose of 5 and 10% per kg and the metformin (500 mg/kg) as reference drug were given orally for 30 days to the diabetic rats. Diabetic rats showed significant (p < 0.001) elevations in plasma blood glucose, thiobarbituric acid-reactive substances and significant reduction in catalase, superoxide dismutase and reduced glutathione activity. Oral administration of 5 and 10% aqueous extract of S. maxima for 30 days restored not only of blood glucose levels but also markers of oxidative stress. Histopathological observations of tissues manifested that the S. maxima administration had the protective and therapeutic effects against fructose-induced abnormalities in diabetic rats. It is concluded that S. maxima is effective in reinstating the antioxidant activity in addition to its antidiabetic effect in type 2 diabetic rats.

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