Dataset Information

Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress.

ABSTRACT:

Introduction

Hyperglycemia promotes myocardial fibrotic lesions through upregulation of PKC and p38 in response to redox changes. The effects of naringin on hyperglycemia-induced myocardial fibrotic changes and its putative effects on PKC-? and p38 protein expression in type 1 rat model of diabetes are hereby investigated.

Methods

Male Sprague-Dawley rats were divided into six groups I-VI. Groups I and II, were orally treated with distilled water {3.0 ml/kg body weight (BW)} and naringin (50 mg/kg BW), respectively. Groups III, IV, V and VI were rendered diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg, BW) and were similarly treated with subcutaneous insulin (8.0 I.U/kg BW, twice daily), naringin (50 mg/kg BW), distilled water (3.0 ml/Kg BW) and ramipril (3.0 mg/kg/BW), respectively. The animals were sacrificed after 56 days by halothane overdose; blood and heart samples removed for further analysis.

Results

The untreated diabetic rats exhibited significantly increased oxidative stress, NADPH oxidase activity, increased cardiac fibrosis, PKC-? and p38 mitogen activated protein kinase expression compared to controls. Naringin treatment significantly ameliorated these changes in diabetic rats compared to the untreated diabetic controls.

Conclusions

Naringin's amelioration of myocardial fibrosis by modulating p38 and PKC-? protein expression possibly through its known antioxidant actions and may therefore be useful in retarding the progression of fibrosis in a diabetic heart.

SUBMITTER: Adebiyi OA

PROVIDER: S-EPMC4788433 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress.

Adebiyi Olubunmi A OA Adebiyi Oluwafeyisetan O OO Owira Peter M O PM

PloS one 20160311 3

<h4>Introduction</h4>Hyperglycemia promotes myocardial fibrotic lesions through upregulation of PKC and p38 in response to redox changes. The effects of naringin on hyperglycemia-induced myocardial fibrotic changes and its putative effects on PKC-β and p38 protein expression in type 1 rat model of diabetes are hereby investigated.<h4>Methods</h4>Male Sprague-Dawley rats were divided into six groups I-VI. Groups I and II, were orally treated with distilled water {3.0 ml/kg body weight (BW)} and n ...[more]

PMID: 26967518

Similar Datasets

Project description:A major consequence of ICU-acquired weakness (ICUAW) is diaphragm weakness, which prolongs the duration of mechanical ventilation. Hyperglycemia (HG) is a risk factor for ICUAW. However, the mechanisms underlying HG-induced respiratory muscle weakness are not known. Excessive reactive oxygen species (ROS) injure multiple tissues during HG, but only one study suggests that excessive ROS generation may be linked to HG-induced diaphragm weakness. We hypothesized that HG-induced diaphragm dysfunction is mediated by excessive superoxide generation and that administration of a specific superoxide scavenger, polyethylene glycol superoxide dismutase (PEG-SOD), would ameliorate these effects.HG was induced in rats using streptozotocin (60 mg/kg intravenously) and the following groups assessed at two weeks: controls, HG, HG?+?PEG-SOD (2,000U/kg/d intraperitoneally for seven days), and HG?+?denatured (dn)PEG-SOD (2000U/kg/d intraperitoneally for seven days). PEG-SOD and dnPEG-SOD were administered on day 8, we measured diaphragm specific force generation in muscle strips, force-pCa relationships in single permeabilized fibers, contractile protein content and indices of oxidative stress.HG reduced diaphragm specific force generation, altered single fiber force-pCa relationships, depleted troponin T, and increased oxidative stress. PEG-SOD prevented HG-induced reductions in diaphragm specific force generation (for example 80 Hz force was 26.4?±?0.9, 15.4?±?0.9, 24.0?±?1.5 and 14.9?±?0.9 N/cm2 for control, HG, HG?+?PEG-SOD, and HG?+?dnPEG-SOD groups, respectively, P <0.001). PEG-SOD also restored HG-induced reductions in diaphragm single fiber force generation (for example, Fmax was 182.9?±?1.8, 85.7?±?2.0, 148.6?±?2.4 and 90.9?±?1.5 kPa in control, HG, HG?+?PEG-SOD, and HG?+?dnPEG-SOD groups, respectively, P <0.001). HG-induced troponin T depletion, protein nitrotyrosine formation, and carbonyl modifications were largely prevented by PEG-SOD.HG-induced reductions in diaphragm force generation occur largely at the level of the contractile proteins, are associated with depletion of troponin T and increased indices of oxidative stress, findings not previously reported. Importantly, administration of PEG-SOD largely ablated these derangements, indicating that superoxide generation plays a major role in hyperglycemia-induced diaphragm dysfunction. This new mechanistic information could explain how HG alters diaphragm function during critical illness.

Project description:Increased oxidative stress by hyperglycemia is a major cause of vascular complications in diabetes. Bird's nest, which is made from the saliva of swiftlets has both medicinal and nutritional values dated back to ancient China. However, its role in improving endothelial dysfunction due to diabetes is yet to be elucidated. The present study examined the protective effect and mechanism of action of the aqueous extract of hydrolyzed edible bird nest (HBN) on endothelium in models of diabetes, in vitro and in vivo. Male db/m+ and db/db mice were orally administered with or without HBN and glibenclamide for 28 days, followed by vascular reactivity studies in mouse aortas. Human umbilical vein endothelial cells (HUVECs) and isolated mouse aorta from C57BL/6J were treated with high glucose (HG), HBN, sialic acid (SA), glibenclamide, and apocynin, respectively. The effects of HBN on reactive oxygen species (ROS) production and nitric oxide (NO) bioavailability were assessed by Western blot, 2',7'-dichlorofluorescin-diacetate (DCF-DA), and 4-amino-5-methylamino-2',7' difluorofluorescein (DAF-FM DA) in HUVECs, isolated mouse aorta, and db/db diabetic mice. HBN significantly reversed the endothelial dysfunction in diabetic mice and isolated mouse aorta. HBN normalized ROS over-production of NOX2 and nitrotyrosine, reversed the reduction of anti-oxidant marker, SOD-1 as well as restored NO bioavailability in both HUVECs challenged with HG and in db/db diabetic mice. Similarly, HG-induced elevation of oxidative stress in HUVECs were reversed by SA, glibenclamide, and apocynin. This attests that HBN restores endothelial function and protects endothelial cells against oxidative damage induced by HG in HUVECs, isolated mouse aorta, and db/db diabetic mice via modulating ROS mechanism, which subsequently increases NO bioavailability. This result demonstrates the potential role of HBN in preserving endothelial function and management of micro- or macrovascular complications in diabetes.

Dataset Information

Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress.

Introduction

Methods

Results

Conclusions

Publications

Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure