The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Gao, Hong‐Fei; Zeng, Zhigang; Zhang, Han; Zhou, Xiaoli; Guan, Lichang; Deng, Weiping; Xu, Li‐Yan

doi:10.1248/bpb.b14-00505

Cited by 57 publications

(46 citation statements)

References 58 publications

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“…It has been reported that activators of GLP-1 receptors can regulate lipid metabolism and homocysteine enzymes (Wang et al, 2014;Gao et al, 2015;Liu et al, 2014;Niu et al, 2015), so we observed the effect of our liraglutide-loaded PLGA microspheres on these. The microspheres have positive effects in improving lipid metabolism and homocysteine enzyme levels.…”

Section: Tablesupporting

confidence: 57%

“…It has been reported that activators of GLP-1 receptors can regulate lipid metabolism and homocysteine enzymes (Wang et al, 2014;Gao et al, 2015;Liu et al, 2014;Niu et al, 2015). From Fig 7, we can see that except for cystathionine beta-synthase, where similar quantities are observed for all groups, the three microsphere groups and the LCIG treatment group have distinct effects on the metabolic enzyme profile.…”

Section: Metabolic Enzymesmentioning

confidence: 53%

“…abnormal lipid levels, inflammatory factors and oxidative stress (Dall et al, 2014;Mebazaa et al, 2013;Abarikwu, 2014). GLP-1 can regulate the blood lipid levels, inflammation, and antioxidant ability of diabetic rats (Ceriello et al, 2005;Pickup, 2004;Gao et al, 2015) and improve the liver, kidney and heart functions (Mells et al, 2012;Zavattaro et al, 2015;Rizzo et al, 2013), and this it was expected that liraglutide could act similarly. The liraglutide PLGA microspheres show improvements in all these measures, and were as effective as the liraglutide injection group.…”

Section: Tablementioning

confidence: 98%

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Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Williams

Branford-White

et al. 2016

European Journal of Pharmaceutical Sciences

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In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.

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Section: Tablesupporting

confidence: 57%

“…It has been reported that activators of GLP-1 receptors can regulate lipid metabolism and homocysteine enzymes (Wang et al, 2014;Gao et al, 2015;Liu et al, 2014;Niu et al, 2015). From Fig 7, we can see that except for cystathionine beta-synthase, where similar quantities are observed for all groups, the three microsphere groups and the LCIG treatment group have distinct effects on the metabolic enzyme profile.…”

Section: Metabolic Enzymesmentioning

confidence: 53%

Section: Tablementioning

confidence: 98%

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Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Williams

Branford-White

et al. 2016

European Journal of Pharmaceutical Sciences

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“…Additionally, atorvastatin increase intrarenal activities of SOD and decrease MDA content . Gao et al (2015) show that liraglutide significantly increased SOD levels in non-alcoholic fatty liver disease. Also, it prevented brain edema, suppressed neuroinflammation following intracerebral hemorrhage (Hou et al, 2012).…”

Section: Discussionmentioning

confidence: 82%

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Shata¹,

Elmorsy²,

Elesawy³

et al. 2017

Afr. J. Pharm. Pharmacol.

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The prevalence of cardiovascular changes markedly increases with deterioration of patient's renal function and can stack up 65 to 70% in end-stage renal disease. A rapid fall in renal function is often associated with uncontrolled congestive heart failure. Beyond their lipid-lowering effect, statins have been shown to protect the heart in different diseases. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue, used to control diabetes. It improves cardiac dysfunction in non-diabetics, but underlying mechanisms remain to some extent, unclear. Fifty two male Sprague-Dawley rats weighing 200 to 250 g were grouped into negative control, positive control, liraglutide treated group (0.3 mg/kg), atorvastatin treated group (10 mg/kg), liraglutide and atorvastatin treated group (0.3 and 10 mg/kg, respectively), liraglutide and atorvastatin treated group (0.15 and 5 mg/kg, respectively). Combination of both drugs significantly reduce creatine phosphokinase isoenzyme (CK-MB) in both doses (p<0.008, p <0.002) and lactate dehydrognase (LDH) (p<0.04, p<0.01). Liraglutide alone or in combination with atorvastatin in both doses (p<0.02, p<0.01 and p<0.01) significantly increased superoxide dismutase (SOD). Atorvastatin alone (p<0.02) or in combination with liraglutide in both doses (p<0.001, p<0.001) induced a significant decrease of malondialdehyde (MDA). Atorvastatin alone (p<0.01) or in combination with liraglutide in both doses induced a significant amelioration of nitric oxide (NO) and cholesterol (p<0.01 and p<0.02). Significant improvements in blood urea nitrogen (BUN) and glucose profile were seen with all tested drugs either single or in combination. Combined implementation of both drugs improves histopathological changes of cardiac muscle fibres. Liraglutide has promising effects on cardiovascular changes in adenine induced chronic nephropathy through modulation of LDH, CK-MB and improvement of NO and SOD. Also, it can mitigate fibrosis and cardiac tissue changes. Its effects markedly increase in conjunction with atorvastatin. Combined administration of liraglutide and atorvastatin in a high dose has a reliable effect on improving outcome in biochemical and histopthological cardiac muscle fibers changes.

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“…These effects were observed in experimental animals but also in the clinical setting. Liraglutide, for example improves metabolic dysfunction and insulin resistance, reduces lipotoxicity in the liver, and counteracts the pathogenesis of nonalcoholic hepatic steatosis [48,49 & ].…”

Section: Effect Of Glucagon-like Peptide-1 To Improve Hepatic Steatosismentioning

confidence: 99%

Glucagon-like peptide-1, glucagon-like peptide-2, and lipid metabolism

Lutz¹,

Osto

2016

Current Opinion in Lipidology

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PURPOSE OF REVIEW: Glucagon-like peptide-1 (GLP-1) is the best known incretin hormone able to potentiate glucose-induced insulin secretion. Moreover, GLP-1 is currently under intensive investigation as a potential crucial mediator of beneficial metabolic effects after bariatric surgery, because of its eating inhibitory, antiobesity, and antidiabetes effects. This review briefly summarizes recent findings on the specific effects of GLP-1 on lipoprotein metabolism. The related hormone GLP-2 is derived from the same precursor gene; its effects on lipoprotein metabolism will also be discussed briefly. RECENT FINDINGS: Pharmacological activation of the GLP-1 system has beneficial effects on obesity-induced alterations of lipoprotein metabolism. These benefits can be observed with direct GLP-1 receptor agonists like liraglutide or exendin-4, but also with inhibitors of dipeptidyl peptidase IV (DPP-IV), which reduce the breakdown of endogenous GLP-1. The role of GLP-2-related pathways on lipid levels and metabolism are less clear, but some effects (e.g. increased intestinal chylomicron output) are opposite to GLP-1. SUMMARY: Activation of the GLP-1-dependent pathways may perhaps translate into a lower cardiovascular risk. Understanding how GLP-1 and GLP-2 regulate and interact in the control of lipoprotein metabolism will set the stage for the development of new strategies to treat dyslipidaemia in obesity, diabetes, and other cardiometabolic diseases. Purpose of review Glucagon-like peptide-1 (GLP-1) is the best known incretin hormone able to potentiate glucose-induced insulin secretion. Moreover, GLP-1 is currently under intensive investigation as a potential crucial mediator of beneficial metabolic effects after bariatric surgery, because of its eating inhibitory, antiobesity, and antidiabetes effects. This review briefly summarizes recent findings on the specific effects of GLP-1 on lipoprotein metabolism. The related hormone GLP-2 is derived from the same precursor gene; its effects on lipoprotein metabolism will also be discussed briefly. Recent findingsPharmacological activation of the GLP-1 system has beneficial effects on obesity-induced alterations of lipoprotein metabolism. These benefits can be observed with direct GLP-1 receptor agonists like liraglutide or exendin-4, but also with inhibitors of dipeptidyl peptidase IV (DPP-IV), which reduce the breakdown of endogenous GLP-1. The role of GLP-2-related pathways on lipid levels and metabolism are less clear, but some effects (e.g. increased intestinal chylomicron output) are opposite to GLP-1. SummaryActivation of the GLP-1-dependent pathways may perhaps translate into a lower cardiovascular risk. Understanding how GLP-1 and GLP-2 regulate and interact in the control of lipoprotein metabolism will set the stage for the development of new strategies to treat dyslipidaemia in obesity, diabetes, and other cardiometabolic diseases.

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The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Cited by 57 publications

References 58 publications

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Glucagon-like peptide-1, glucagon-like peptide-2, and lipid metabolism

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