Combined treatment of diabetic nephropathy with alprostadil and calcium dobesilate

Qin, Linling; Qin, Wenjun; Wang, Jianfei; Lin, Lin

doi:10.3892/etm.2017.5115

Cited by 10 publications

(17 citation statements)

References 21 publications

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“…SCr, BUN, and serum 2 -MG are common biochemical markers reflecting glomerular damage. 24 We found that there were no significant difference in SCr, BUN, and serum 2 -MG among the groups, which was similar to the results reported by Abdelraouf et al, 21 who found no significant fluctuation in SCr in any of the rats treated with PMB at 5 mg/kg body weight daily for up to 10 days. These findings indicated that PMB administered at a lower dose such as 4 or 5 mg/kg body weight daily may not result in injury to renal glomeruli.…”

Section: Discussionsupporting

confidence: 91%

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

Luo

et al. 2018

Hum Exp Toxicol

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The receptor megalin plays an important role in the accumulation of polymyxin B (PMB) in renal cells in vitro. This study aimed to examine the effects of cytochrome c (cyto c), a typical megalin ligand, on renal accumulation and nephrotoxicity of PMB in vivo. Thirty Sprague-Dawley rats were randomly divided into the vehicle control group, PMB group, PMB + cyto c 50, 100, or 200 mg/kg group, respectively, and were treated with intravenous cyto c 30 min before the administration of PMB 4.0 mg/kg once a day for consecutive 5 days. On the 4th day after administration, 24 h urine was collected to determine N-acetyl-β-D-glucosaminidase excretion. Six hours after the last injection on the 5th day, kidneys were harvested to assay PMB concentration and observe pathological alterations, and blood samples were collected to assay serum creatinine (SCr), blood urea nitrogen (BUN), and blood β2-microglobulin (β2-MG) levels. Cyto c 50, 100, and 200 mg/kg decreased the accumulation of PMB in the kidney by 18.5%, 39.1% ( p < 0.01), and 36.8% ( p < 0.01), respectively, and reduced 24 h N-acetyl-β-D- glucosaminidase excretion by 22.5% ( p < 0.05), 40.4% ( p < 0.01), and 40.4% ( p < 0.01), respectively. Kidney pathological damage induced by PMB was markedly reduced by cyto c 100 mg/kg and 200 mg/kg. However, there were no significant differences in SCr, BUN, and blood β2-MG levels among the groups. These results indicated that cyto c may inhibit the renal accumulation and nephrotoxicity of PMB in a rat model, further proving the role of megalin in the accumulation of PMB.

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Section: Discussionsupporting

confidence: 91%

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

Luo

et al. 2018

Hum Exp Toxicol

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“…Alprostadil can protect the microcirculation and inhibit inflammatory responses, and, as is known, have antiinflammatory and anti-apoptotic effects on the myocardium [24][25][26][27]. We found that alprostadil reversed the decline of cell activity, reduced LDH and troponin levels, and down-regulated the expression of inflammatory factors in H9c2 cells treated with LPS, which suggests that alprostadil had a protective effect on myocardial cells.…”

Section: Discussionsupporting

confidence: 62%

“…Clinical research has demonstrated that alprostadil can reduce the expression of inflammatory factors such as myeloperoxidase (MPO), TNF-α, and IL-6 in the treatment of ischemia reperfusion injury, contrast nephropathy, and diabetic nephropathy etc. [24][25][26][27]. Furthermore, PGE1 improved the myocardial microcirculation and alleviated apoptosis of myocardial cells [28,29].…”

mentioning

confidence: 99%

Alprostadil attenuates LPS-induced cardiomyocyte injury by inhibiting the Wnt5a/JNK/NF-κB pathway

Dong

Guan

et al. 2019

Herz

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Background Clinical research has demonstrated that alprostadil has an anti-inflammatory effect; however, to date, its molecular mechanisms remain unclear. This study aimed to examine the anti-inflammatory activity and related mechanisms of alprostadil in lipopolysaccharide (LPS)-treated H9c2 cells. Methods Cell morphology was observed under an inverted light microscope, while cell viability was assessed with the 3‑(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assays (ELISA) were conducted to study biochemical indicators of cellular damage, such as released lactate dehydrase (LDH) and troponin, and inflammatory cytokine levels including interleukin-1β (IL-1β), IL-6, IL-17, and tumor necrosis factor-α (TNF-α). The mRNA expression levels of Wnt5a, c‑jun N‑terminal kinase (JNK), and nuclear factor kappa B (NF-κB) were further investigated by real-time quantitative polymerase chain reaction (RT-PCR). The effects of alprostadil on the Wnt5a/JNK/NF-κB pathway in H9c2 cells was examined by Western blotting. Results Alprostadil increased the cell viability of LPS-stimulated H9c2 cells, reduced LDH and troponin production, and attenuated IL-1β, IL-6, IL-17, and TNF-α secretion. Moreover, alprostadil reduced the mRNA expression of Wnt5a, JNK, and NF-κB and decreased the expression of Wnt5a, NF-κB, and the ratio of p‑JNK/JNK in H9c2 cells treated with LPS. The siWnt5a or JNK inhibitor SP600125 significantly augmented the inhibitory effects of alprostadil on the Wnt5a/JNK/NF-κB pathway. Conclusion Our results show that alprostadil has anti-inflammatory effects and could attenuate LPS-induced injury in H9c2 cardiomyocytes via the Wnt5a/JNK/NF-κB pathway.

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“…CaD is applied for the treatment of diabetic microvascular diseases, especially for diabetic retinopathy because of its angioprotective properties (Suschek et al, 1997; Brunet et al, 1998; Brunet et al, 1998; Leal et al, 2010). Clinical studies have noted that alprostadil combined with CaD is widely applied for the treatment of renal disease (Qin et al, 2017), and CaD has been confirmed to be effective in maintaining the construction of the vascular endothelium and enhancing renal function (John and Ning, 2016). However, the specific mechanism is not yet clear.…”

Section: Discussionmentioning

confidence: 99%

Calcium Dobesilate Restores Autophagy by Inhibiting the VEGF/PI3K/AKT/mTOR Signaling Pathway

Wang

Tang

et al. 2019

Front. Pharmacol.

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Objective: Calcium dobesilate (CaD), an effective drug for the treatment of diabetic microvascular complications, especially diabetic retinopathy, is widely used in the clinic. Interestingly, several studies have indicated that CaD is therapeutic for diabetic kidney disease (DKD). Recently, evidence has indicated that altered vascular endothelial growth factor (VEGF) expression and decreased autophagy are the main pathological mechanisms of proteinuria. Thus, this study was conducted to explore the effect of CaD on restoring autophagy in DKD and the possible signaling pathway between VEGF and autophagy. Methods: Obese mice with spontaneous diabetes (KK-Ay) and high-fat diet- and streptozotocin-induced diabetic mice (HFD/STZ) were used in this study. Biochemical staining, western blotting, and immunohistochemistry were conducted to determine the angioprotective effect of CaD and the underlying mechanism between autophagy and VEGF/VEGFR. Results: Our results showed that CaD was capable of reducing albuminuria and restoring renal histological changes in KK-Ay and HFD/STZ-induced diabetic mice. CaD restored autophagy by decreasing the protein expression of LC3 II, Atg5, and beclin 1 and increasing the expression of P62. Moreover, CaD reduced the activation of the autophagy-related PI3K/AKT/mTOR pathway possibly via decreasing VEGF and downregulating VEGF receptor 2. Conclusion: Overall, CaD, as a novel potential therapeutic drug for DKD, plays a key role in protecting renal function and restoring autophagy by blocking VEGF/VEGFR2 and inhibiting the PI3K/AKT/mTOR signaling pathway.

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Combined treatment of diabetic nephropathy with alprostadil and calcium dobesilate

Cited by 10 publications

References 21 publications

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

Alprostadil attenuates LPS-induced cardiomyocyte injury by inhibiting the Wnt5a/JNK/NF-κB pathway

Calcium Dobesilate Restores Autophagy by Inhibiting the VEGF/PI3K/AKT/mTOR Signaling Pathway

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