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Naringenin accords hepatoprotection from streptozotocin induced diabetes in vivo by modulating mitochondrial dysfunction and apoptotic signaling cascade.

ABSTRACT: Diabetic complications cause noticeable liver damage, which finally progresses to diabetic hepatopathy. Nutritive antioxidants not only reduce the liver damage, but also prevent it by modulating the release of various proteins involved in apoptotic signaling cascades. This study explores the molecular mechanisms underlying diabetes-induced liver damage and its modulation by naringenin. Antioxidant status, liver & kidney biomarker enzymes, reactive oxygen species (ROS) generation, mitochondrial membrane potential, expression of apoptotic proteins like Bax (bcl-2 associated X), Bcl-2 (b-cell Lymhoma-2), Caspase-3, Caspase-9, AIF (Apoptosis inducing factor) and Endo-G (Endonuclease-G) were studied in streptozotocin induced diabetic rats. Significant hyperglycemia, disturbed antioxidant status, altered carbohydrate metabolizing enzymes, increased ROS and lipid peroxidation; decreased mitochondrial membrane potential and enhanced release of AIF and Endo-G were observed. Hyperglycemia also affected apoptosis and its related genes at both transcriptional and translational level (Caspase-3 & 9, Bax and Bcl-2) in the liver of diabetic rats. Naringenin, a flavonone, exerted anti-hyperglycemic effect and was able to prevent oxidative stress and resultant apoptotic events caused due to diabetes-induced hepatotoxicity. Thus, our study shows, a protective effect of naringenin against diabetes induced liver damage and redox imbalance, which could further be exploited for the management of diabetic hepatopathy.

SUBMITTER: Kapoor R

PROVIDER: S-EPMC5598533 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Naringenin accords hepatoprotection from streptozotocin induced diabetes in vivo by modulating mitochondrial dysfunction and apoptotic signaling cascade.

Kapoor Radhika R Kakkar Poonam P

Toxicology reports 20140813

Diabetic complications cause noticeable liver damage, which finally progresses to diabetic hepatopathy. Nutritive antioxidants not only reduce the liver damage, but also prevent it by modulating the release of various proteins involved in apoptotic signaling cascades. This study explores the molecular mechanisms underlying diabetes-induced liver damage and its modulation by naringenin. Antioxidant status, liver & kidney biomarker enzymes, reactive oxygen species (ROS) generation, mitochondrial m ...[more]

PMID: 28962270

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Project description:Skeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training Mitochondrial dysfunction has long been implicated to play a causative role in development of type 2 diabetes (T2DM). However, a growing number of recent studies provide data that mitochondrial dysfunction is a consequence of T2DM development. The aim of our study is to clarify in further detail the causal role of mitochondrial dysfunction in T2DM by a comprehensive ex vivo analysis of mitochondrial function combined with global gene expression analysis in muscle of pre-diabetic newly diagnosed untreated T2DM subjects and long-standing insulin treated T2DM subjects compared with age- and BMI-matched controls. In addition, we assessed the impact of long-term interval exercise training on physical activity performance, mitochondrial function and glycemic control in long-standing insulin-treated T2DM subjects. Ex vivo mitochondrial density, quality and functioning was comparable between pre-diabetic subjects and matched controls, however, gene expression analysis showed a switch from carbohydrate toward lipids as energy source in pre-diabetes subjects. In contrast, long-term insulin treated T2DM subjects had slightly decreased mitochondrial density and ex vivo function. Expression of Krebs cycle and OXPHOS related genes were decreased, indicating a decreased capacity to use lipids as an energy source. The insulin-treated T2DM subjects had a lower physical activity level than pre-diabetic and normoglycemic subjects. A 52 weeks exercise training of these subjects increased submaximal oxidative efficiency, increased in vivo PCr recovery rate, as well as mildly increased in vitro mitochondrial function. Gene expression of β-oxidation, Krebs cycle and OXPHOS-related genes was increased. Our data demonstrate that mitochondrial dysfunction is rather a consequence than a causative factor in T2DM development as it was only detected in overt diabetes and not in early diabetes. Regular exercise training stabilized exogenous insulin requirement and improved mitochondrial functioning, fatty acid oxidation and general physical work load capacity in long-standing insulin-treated T2DM subjects. As such, the present study shows for the first time that long-term exercise interventions are beneficial in this group of complex diabetes patient and may prevent further metabolic deterioration. Insulin-treated T2DM subjects before and after 52 weeks of exercise training (T2DM_0 and T2DM_52), normoglycemic controls (NGT) and pre-diabetes subjects (IGT) and were selected. RNA was extracted from skeletal muscle biopsies and hybridized on Affymetrix microarrays.

Dataset Information

Naringenin accords hepatoprotection from streptozotocin induced diabetes in vivo by modulating mitochondrial dysfunction and apoptotic signaling cascade.

Publications

Naringenin accords hepatoprotection from streptozotocin induced diabetes in vivo by modulating mitochondrial dysfunction and apoptotic signaling cascade.

Similar Datasets

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