Fenofibrate improves vascular endothelial function in diabetic mice

Xin, Rujuan; An, Duopeng; Liu, Ying; Fu, Jin; Huang, Fang

doi:10.1016/j.biopha.2019.108722

Cited by 13 publications

(11 citation statements)

References 53 publications

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“…To determine whether the effects observed in vitro might translate into an improvement in vivo, an experimental model of STZ‐induced hyperglycemia was used to produce ED (Xin et al, 2019), It is well known that sustained hyperglycemic conditions induce the impairment of several critical functions of endothelial cells, together with an increase in ARG expression and activity (Hemling et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Polyphenolic compounds of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae) improved endothelial dysfunction through arginase inhibition

Minozzo

Andrade

Vellosa

et al. 2020

Phytotherapy Research

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Euphorbia umbellata is used for its anti-inflammatory properties; however, there are limited data available regarding its effects on vascular function. Its bark is rich in polyphenolic compounds, which potentially improve endothelial dysfunction (ED). This study proposes to investigate the effects of E. umbellata bark extracts and its polyphenolic compounds on arginase (ARG) activity and nitric oxide (NO)-related targets.Chromatographic procedures were used for the chemical characterisation of the extracts. Furthermore, in silico (molecular docking), in vitro (ARG inhibition), in vivo (streptozotocin-induced hyperglycemia model), and ex vivo (L-arginine metabolism, vascular reactivity, western blot, and biochemical) techniques were carried out. Quercetin, gallic acid, and ellagic acid were identified in the extracts. In silico screening predicted that gallic acid and quercetin would have the most promising interactions with ARG -identified cavities. This was confirmed in vitro as both compounds had a direct inhibitory effect on ARG, as was the case regarding the extracts. Oral treatment preserved endothelium-dependent vasodilation through ARG inhibition together with an increase in L-arginine bioavailability and endothelial NO synthase expression. Biochemical parameters determined the lack of toxicity for sub-chronic treatment. E. umbellata bark extracts and its compounds can contribute to ED treatment, at least partly, through the inhibition of vascular ARG.

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Section: Resultsmentioning

confidence: 99%

Polyphenolic compounds of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae) improved endothelial dysfunction through arginase inhibition

Minozzo

Andrade

Vellosa

et al. 2020

Phytotherapy Research

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“…[ 12 29 30 ] Fenofibrate has been noted to improve the function of endothelium mediated renal damage by increasing the bioavailability of NO and reducing the oxidative stress. [ 10 11 12 13 14 15 16 17 18 19 20 21 22 31 32 ] The vascular protecting potential of fenofibrate in preventing the development of vascular endothelial dysfunction and kidney injury may be attributed to its antihyperlipidemic property and/or its pleiotropic actions such as activation of eNOS and generation of NO and the consequent reduction in oxidative stress to improve the integrity and function of the endothelium and renal functions in nicotine administered rats. Nicotine decreases in expression of mRNA for eNOS and its treatment with fenofibrate prevented the nicotine induced decrease in eNOS.…”

Section: Discussionmentioning

confidence: 99%

“…[ 10 15 ] It has been also noted that the fenofibarte upregulates the expression of eNOS, thus has been reported to ameliorate nicotine-induced endothelial dysfunction by reducing hyperlipidemia and oxidative stress. [ 12 16 ] In addition, in our laboratory, we have shown that treatment with fenofibrate and concurrent administration of benfotiamine, prevented the development of diabetic nephropathy indicating fenofibrate-mediated renoprotection. [ 10 ] These studies certainly suggest a vascular and reno-protective potential of fenofibrate.…”

Section: Introductionmentioning

confidence: 99%

Fenofibrate prevents nicotine-induced acute kidney injury: Possible involvement of endothelial nitric oxide synthase

Chakkarwar¹,

Kawtikwar²

2021

Indian J Nephrol

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Objective: The present study investigated the possible effect of fenofibrate (peroxisome proliferator-activated receptors-α agonist) in nicotine-induced acute kidney injury (AKI) in rats. Materials and Methods: Nicotine (2 mg/kg/day, intraperitoneally) was administered for 4 weeks to induce AKI in rats. Lipid profile and renal oxidative stress were measured and expression of mRNA for eNOS was assessed using reverse transcription-polymerase chain reaction along with serum and renal tissue nitrite levels. Serum creatinine, blood urea nitrogen and microproteinuria were estimated along with the kidney histology, as markers of kidney function. Treatment with fenofibrate (30 mg/kg per oral, 4 weeks) was initiated 3 days before the administration of nicotine and continued for 4 weeks from the day of administration of nicotine. Results: Nicotine administered rats developed apparent AKI confirmed by elevated markers of kidney function and noticeable glomerulosclerosis and tubular cell degeneration. Nicotine decreases the expression of mRNA for eNOS, along with serum and renal tissue nitrite levels. In addition, nicotine showed significantly lipid alteration beside decrease oxidative stress, assessed in terms of increase in serum thiobarbituric acid reactive substance and a marked decrease in tissue reduced glutathione. However, fenofibrate significantly prevented the development of nicotine-AKI by reducing serum creatinine, BUN, and urinary protein, normalizing the lipid profile, reducing renal oxidative stress, increases the eNOS expression and concentration of serum and renal nitrate levels. Conclusion: Fenofibrate attenuates nicotine-induced AKI, via its antihyperlipidemic and antioxidant property. Moreover, fenofibrate induced upregulation of eNOS expression additionally play key roles in the improvement of nicotine-induced AKI could be the future alternative.

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“…Increased reactive oxygen species (ROS) accumulation in the mitochondria of coronary artery endothelial cells was found in diabetic rats [ 12 ]. Previous studies verified that antioxidants and superoxide dismutase restored endothelium-dependent vasodilation of streptozocin (STZ)-induced diabetic rats [ 14 ]. ROS scavenger N-acetyl-L-cysteine (NAC) pretreatment alleviated high glucose (HG)-induced endothelial dysfunction in human microvascular endothelial cell-1 (HMEC-1) cells [ 15 ].…”

Section: Introductionmentioning

confidence: 91%

Dihydromyricetin Improves Endothelial Dysfunction in Diabetic Mice via Oxidative Stress Inhibition in a SIRT3-Dependent Manner

Hua

Zhang

Gong

et al. 2020

IJMS

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Dihydromyricetin (DHY), a flavonoid component isolated from Ampelopsis grossedentata, exerts versatile pharmacological activities. However, the possible effects of DHY on diabetic vascular endothelial dysfunction have not yet been fully elucidated. In the present study, male C57BL/6 mice, wild type (WT) 129S1/SvImJ mice and sirtuin 3 (SIRT3) knockout (SIRT3-/-) mice were injected with streptozotocin (STZ, 60 mg/kg/day) for 5 consecutive days. Two weeks later, DHY were given at the doses of 250 mg/kg by gavage once daily for 12 weeks. Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) level, endothelium-dependent relaxation of thoracic aorta, reactive oxygen species (ROS) production, SIRT3, and superoxide dismutase 2 (SOD2) protein expressions, as well as mitochondrial Deoxyribonucleic Acid (mtDNA) copy number, in thoracic aorta were detected. Our study found that DHY treatment decreased FBG and HbA1c level, improved endothelium-dependent relaxation of thoracic aorta, inhibited oxidative stress and ROS production, and enhanced SIRT3 and SOD2 protein expression, as well as mtDNA copy number, in thoracic aorta of diabetic mice. However, above protective effects of DHY were unavailable in SIRT3-/- mice. The study suggested DHY improved endothelial dysfunction in diabetic mice via oxidative stress inhibition in a SIRT3-dependent manner.

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Fenofibrate improves vascular endothelial function in diabetic mice

Cited by 13 publications

References 53 publications

Polyphenolic compounds of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae) improved endothelial dysfunction through arginase inhibition

Polyphenolic compounds of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae) improved endothelial dysfunction through arginase inhibition

Fenofibrate prevents nicotine-induced acute kidney injury: Possible involvement of endothelial nitric oxide synthase

Dihydromyricetin Improves Endothelial Dysfunction in Diabetic Mice via Oxidative Stress Inhibition in a SIRT3-Dependent Manner

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