Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update

Chen, Ming-Fong; Chiang, Wen‐Chih; Lin, Shuei‐Liong; Tsai, Tun‐Jun

doi:10.1186/s12929-017-0390-4

Cited by 29 publications

(16 citation statements)

References 93 publications

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“…Experimental studies have shown that its administration causes immune modulation in a dose-dependent manner. This is exemplified by increased leukocyte deformability and chemotaxis, decreased endothelial leukocyte adhesion, neutrophil degranulation, TNF-α production and NK cell activity (Brie et al 2016;Chen et al 2017). Garcia et al (2015) showed that PTX reduces inflammatory factors such as TNF-α, interleukin-6, and inducible nitric oxide synthase, which can improve diabetic neuropathy by reducing inflammation.…”

Section: Discussionmentioning

confidence: 99%

Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers

Degen

Krynytska

Kamyshnyі

2020

Endocrine Regulations

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Objective. The aim of the present study was to investigate the transcriptional activity of the GLP-1R, DPP-4, SGLT-1, INSR, and IGF-1R genes in GALT cells of rats with streptozotocin-induced diabetes in both untreated and treated with pentoxifylline, as a non-specific blocker of TNF-α.Methods. The expression of GLP-1R, DPP-4, SGLT-1, INSR, and IGF-1R genes in GALT cells of rats was studied by real time quantitative polymerase chain reaction.Results. It was shown that the development of diabetes was accompanied by the decrease of GLP-1R and an increase of DPP-4 genes expression in rat ileum. The administration of pentoxifyl-line to diabetic animals led to an increase in the transcriptional activity of GLP-1R on the 4th week and decrease in transcriptional activity of DPP-4 on the 2nd and 4th weeks of the experiment. An increase in the normalized expression of SGLT-1 on the 4th week of the experimental diabetes was also noted, while the administration of pentoxifylline to diabetic animals did not lead to significant changes in this index. The transcriptional activity of the INSR and IGF-1R genes was reduced in diabetic rats and the administration of the non-specific TNF-α blocker – pentoxifylline led to a significant increase only for INSR gene in animals on the 4th week of the experimental diabetes.Conclusions. The expression of incretins, glucose transporters, and pro-inflammatory cytokines (e.g. TNF-α) in immune cells may be used as markers of several autoimmune pathologies progression such as type 1 diabetes due to their effect on the balance of pro- and anti-inflammatory factors.

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Section: Discussionmentioning

confidence: 99%

Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers

Degen

Krynytska

Kamyshnyі

2020

Endocrine Regulations

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“…Despite some advancements in the understanding of proteinuria pathogenesis, there is still a lack of therapies that work against proteinuria other than using the renin-angiotensin system (RAS) inhibitor as the gold standard [5], such as angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Unfortunately, RAS blocking slows down but does not preclude the progression of kidney disease [15] and increases the potential risk of hyperkalemia [16]. Immunosuppressive treatment with corticosteroids has shown some effect in remission of proteinuria although a certain percentage of patients do not respond to treatment and are labeled steroid resistant [17].…”

Section: Introductionmentioning

confidence: 99%

“…Glucocorticoid therapy can be resistant or dependent and can also cause many adverse reactions [17,18]. us, it is crucial to search for more safe and effective drugs in treating proteinuria and its primary diseases based on their pharmacological mechanisms [15].…”

Section: Introductionmentioning

confidence: 99%

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Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

Hao

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Shuangbai Tablets (SBT), a traditional herbal mixture, has shown substantial clinical efficacy. However, a systematic mechanism of its active ingredients and pharmacological mechanisms of action against proteinuria continues being lacking. A network pharmacology approach was effectual in discovering the relationship of multiple ingredients and targets of the herbal mixture. This study aimed to identify key targets, major active ingredients, and pathways of SBT against proteinuria by network pharmacology approach combined with thin layer chromatography (TLC). Human phenotype (HP) disease analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking were used in this study. To this end, a total of 48 candidate targets of 118 active ingredients of SBT were identified. Network analysis showed PTGS2, ESR1, and NOS2 to be the three key targets, and beta-sitosterol, quercetin, and berberine were the three major active ingredients; among them one of the major active ingredients, quercetin, was discriminated by TLC. These results of the functional enrichment analysis indicated that the most relevant disease including these 48 candidate proteins is proteinuria, SBT treated proteinuria by sympathetically regulating multiple biological pathways, such as the HIF-1, RAS, AGE-RAGE, and VEGF signaling pathways. Additionally, molecular docking validation suggested that major active ingredients of SBT were capable of binding to HIF-1A and VEGFA of the main pathways. Consequently, key targets, major active ingredients, and pathways based on data analysis of SBT against proteinuria were systematically identified confirming its utility and providing a new drug against proteinuria.

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“…PTX is a methylxanthine derivative with potent hemorrheologic properties and is a non-specific phosphodiesterase inhibitor used in the treatment of peripheral vascular diseases (8,9). PTX exhibits many pharmacological effects such as immuno-modulatory, anti-inflammatory, and antiproliferative effects; inhibition of platelet aggregation, amelioration of the microcirculation, decrease in blood viscosity, increase in erythrocyte deformability, and downregulation of several pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) (10).…”

Section: Biochemical Analysis and Renal Function Assessment Introductionmentioning

confidence: 99%

The Protective Effects of Pentoxifylline on Contrast Induced Nephropathy in Rats

Şahin¹,

Karataş²,

Koc³

et al. 2018

Akd Med J

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Objective: Pentoxifylline (PTX), which has antioxidant and immunomodulatory effects, has been shown to attenuate renal ischemia-reperfusion injury. We aimed to investigate whether PTX might have a preventive role against the development of contrast induced nephropathy (CIN). Material and Methods: A total of 24 Wistar-albino female rats were randomly divided into four groups (n=6 each) as follows; control (C), contrast material (CM), PTX, and PTX+CM. Except the control and CM groups, the groups were given PTX once daily orally for 5 days. CIN was induced by administration of intravenous high-osmole contrast material-diatrizoate (6 mL/kg) after 48 hour of dehydration. Basal and post-CIN kidney function parameters, inflammatory parameters, serum and renal tissue oxidative stress markers (serum levels of advanced oxidation protein product and malondialdehyde), and histopathological lesions were assessed. Results: The increase in serum creatinine and blood urea nitrogen levels was significantly higher only in the CM group (P<0.05). Absolute changes of serum creatinine levels in the PTX, PTX+CM and C groups were significantly lower than those observed in the CM group (P<0.05). There was no significant decrease in creatinine clearance in any group except CM. The differences among the groups regarding the absolute change in creatinine clearance were not significant. Serum levels of advanced oxidation protein product and malondialdehyde were significantly lower in PTX+CM than those in CM (P<0.05). Histopathological lesions in the CM group were more advanced (P<0.05). Conclusion: In conclusion, the study suggests that PTX may prevent CIN.

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Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update

Cited by 29 publications

References 93 publications

Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers

Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers

Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

The Protective Effects of Pentoxifylline on Contrast Induced Nephropathy in Rats

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