Fenofibrate Ameliorates Oxidative Stress-Induced Retinal Microvascular Dysfunction in Diabetic Rats

Li, Jun; Wang, Peipei; Chen, Zhen; Yu, Songping; Xu, Huiwen

doi:10.1080/02713683.2018.1501072

Cited by 14 publications

(16 citation statements)

References 42 publications

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“…Consistent with these previous reports, in the present study, HUCB‐MNC treatment abrogated the increased expression of VEGF in bladders of diabetic rats 4 weeks after the induction of diabetes. Previous studies showed that retinal VEGF gene and protein expression increased significantly in diabetic rats . Furthermore, earlier data reported a permanent increase in renal VEGF gene expression after 3 weeks of diabetes but not in long‐term diabetes .…”

Section: Discussionmentioning

confidence: 92%

“…Previous studies showed that retinal VEGF gene and protein expression increased significantly in diabetic rats. 62,63 Furthermore, earlier data reported a permanent increase in renal VEGF gene expression after 3 weeks of diabetes but not in long-term diabetes. 64 Conversely, Jang et al 65 showed that HUCB-derived mesenchymal stem cells had beneficial effects on renal ischemia-reperfusion injury through humoral effects and the induction of VEGF secretion.…”

Section: Hucb-mncs May Exert Beneficial Effects On Contractions Inducmentioning

confidence: 96%

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Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin‐induced diabetic rats

Kaya‐Sezginer

Yilmaz‐Oral

Gür

2019

LUTS

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Objective This study evaluated the effect of human umbilical cord blood mononuclear cells (HUCB‐MNCs) on bladder dysfunction in streptozotocin (STZ; 35 mg/kg, i.v.)‐induced diabetic rats. Methods Adult male Sprague–Dawley rats (n = 30) were equally divided into three groups: control group, STZ‐diabetic group, and HUCB‐MNC‐treated group (1 × 106 cells). HUCB‐MNCs were isolated by density gradient centrifugation from eight healthy donors and injected into the corpus cavenosum in STZ‐diabetic rats 4 weeks after the induction of diabetes. Studies were performed 4 weeks after HUCB‐MNC or vehicle injection. In vitro organ bath studies were performed on bladder strips, whereas protein expression of hypoxia‐inducible factor (HIF)‐1α, vascular endothelial growth factor (VEGF), and α‐smooth muscle actin (SMA) in the bladder and the ratio of smooth muscle cells (SMCs) to collagen were determined using western blotting and Masson trichrome staining. Results Neurogenic contractions of detrusor smooth muscle strips were 55% smaller in the diabetic group than control group (P < 0.05); these contractions were normalized by HUCB‐MNC treatment. In addition, HUCB‐MNC treatment restored the impaired maximal carbachol‐induced contractile response in detrusor strips in the diabetic group (29%; P < 0.05). HUCB‐MNC treatment improved the KCl‐induced contractile response in the diabetic bladder (68%; P < 0.05), but had no effect on ATP‐induced contractile responses. Increased expression of HIF‐1α and VEGF protein and decreased expression of α‐SMA protein and the SMC/collagen ratio in diabetic rats were reversed by HUCB‐MNC. Conclusion Administration of HUCB‐MNCs facilitates bladder function recovery, which is likely related to downregulation of HIF‐1α expression and attenuation of fibrosis in STZ‐diabetic rats.

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Section: Discussionmentioning

confidence: 92%

Section: Hucb-mncs May Exert Beneficial Effects On Contractions Inducmentioning

confidence: 96%

Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin‐induced diabetic rats

Kaya‐Sezginer

Yilmaz‐Oral

Gür

2019

LUTS

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“…Previous studies have suggested that that fenofibrate exerts robust protective effects against DR in type 2 diabetic patients and type 1 diabetic animal models [ 27 , 28 ]. The potential therapeutic mechanisms of fenofibrate on retinal microvascular dysfunctions induced by diabetes include the restoration of VEGF and the reduction of oxidative stress in diabetic rats [ 29 ]. As CPA4-1 did not alter blood glucose level and HbA1c of db/db mice compared with those of the db/db mice group, CPA4-1 might act as a supplement for the prevention of BRB breakage and retinal acellular capillary formation, without altering blood glucose level or HbA1c of diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

The Herbal Combination CPA4-1 Inhibits Changes in Retinal Capillaries and Reduction of Retinal Occludin in db/db Mice

Kim

et al. 2020

Antioxidants

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Increased formation of advanced glycation end products (AGEs) plays an important role in the development of diabetic retinopathy (DR) via blood-retinal barrier (BRB) dysfunction, and reduction of AGEs has been suggested as a therapeutic target for DR. In this study, we examined whether CPA4-1, a herbal combination of Cinnamomi Ramulus and Paeoniae Radix, inhibits AGE formation. CPA4-1 and fenofibrate were tested to ameliorate changes in retinal capillaries and retinal occludin expression in db/db mice, a mouse model of obesity-induced type 2 diabetes. CPA4-1 (100 mg/kg) or fenofibrate (100 mg/kg) were orally administered once a day for 12 weeks. CPA4-1 ( the half maximal inhibitory concentration, IC50 = 6.84 ± 0.08 μg/mL) showed approximately 11.44-fold higher inhibitory effect on AGE formation than that of aminoguanidine (AG, the inhibitor of AGEs, IC50 = 78.28 ± 4.24 μg/mL), as well as breaking effect on AGE-bovine serum albumin crosslinking with collagen (IC50 = 1.30 ± 0.37 μg/mL). CPA4-1 treatment ameliorated BRB leakage and tended to increase retinal occludin expression in db/db mice. CPA4-1 or fenofibrate treatment significantly reduced retinal acellular capillary formation in db/db mice. These findings suggested the potential of CPA4-1 as a therapeutic supplement for protection against retinal vascular permeability diseases.

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“…Additional therapeutic approaches include: Thiazolidinediones (such as pioglitazone and troglitazone) and synthetic ligands of PPARγ that lead, indirectly, to an increment in production and secretion of adiponectin resulting in the suppression of PASMC proliferation [85]. In the same way, fenofibrate, a PPARγ agonist, ameliorates endothelial functions by reducing levels of inflammation and increasing adiponectin [86,87]. Among antihypertensive drugs, renin–angiotensin system (RAS) blockers have been demonstrated to improve plasma adiponectin levels; specifically, they were more effective than amlodipine, doxazosin, and metoprolol [88,89].…”

Section: Adiponectin Modulation In the Treatment Of Pulmonary Hypementioning

confidence: 99%

“…Finally, promising results have been shown by adipose-derived stem cells (ADSCs) on PAH. Li et al [86] investigated the effects of ADSCs coupled with adiponectin on PAH showing that the ADSCs–adiponectin administration via the jugular vein in mice attenuates the hemodynamic changes and vascular remodeling of PAH (mPAP: 21.44 ± 0.89 mmHg versus 32.62 ± 1.77 mmHg in the PAH group, p < 0.05). Furthermore, the combination of adiponectin and ADSC therapy improved the pulmonary hemodynamics more than ADSC therapy alone (mPAP: 21.44 ± 0.89 mmHg versus 27.11 ± 2.12, p < 0.05).…”

Section: Adiponectin Modulation In the Treatment Of Pulmonary Hypementioning

confidence: 99%

Pulmonary Hypertension and Obesity: Focus on Adiponectin

Perrotta

Nigro

Mollica

et al. 2019

IJMS

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Pulmonary hypertension is an umbrella term including many different disorders causing an increase of the mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Recent data revealed a strong association between obesity and pulmonary hypertension. Adiponectin is a protein synthetized by the adipose tissue with pleiotropic effects on inflammation and cell proliferation, with a potential protective role on the pulmonary vasculature. Both in vivo and in vitro studies documented that adiponectin is an endogenous modulator of NO production and interferes with AMP-activated protein kinase (AMPK) activation, mammalian target of rapamycin (mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling preventing endothelial dysfunction and proliferation. Furthermore, adiponectin ameliorates insulin resistance by mediating the biological effects of peroxisome proliferator-activated receptor-gamma (PPARγ). Therefore, adiponectin modulation emerged as a theoretical target for the treatment of pulmonary hypertension, currently under investigation. Recently, consistent data showed that hypoglycemic agents targeting PPARγ as well as renin–angiotensin system inhibitors and mineralocorticoid receptor blockers may influence pulmonary hemodynamics in different models of pulmonary hypertension.

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Fenofibrate Ameliorates Oxidative Stress-Induced Retinal Microvascular Dysfunction in Diabetic Rats

Abstract: FA prevents the retinal microvascular dysfunction induced by diabetes, likely by restoring VEGF and P-p65 levels, and possibly by reducing oxidative stress and TXNIP expression.

Cited by 14 publications

References 42 publications

Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin‐induced diabetic rats

Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin‐induced diabetic rats

The Herbal Combination CPA4-1 Inhibits Changes in Retinal Capillaries and Reduction of Retinal Occludin in db/db Mice

Pulmonary Hypertension and Obesity: Focus on Adiponectin

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