Protective effects of tadalafil on damaged podocytes in an adriamycin-induced nephrotic syndrome model

Tomita, Natsumi; Hotta, Yuji; Naiki-Ito, Aya; Sanagawa, Akimasa; Kataoka, Tomoya; Furukawa‐Hibi, Yoko; Takahashi, Satoru; Kimura, Kazunori

doi:10.1016/j.jphs.2022.03.003

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…11,12 AN rat model was built by a single adriamycin tail vein injection and applied extensively in nephrology studies due to its stability and similarity to human nephrotic syndrome. [13][14][15] After modeling, the rats developed heavy proteinuria, impaired renal function, and notable morphological changes, such as tubular lumen dilatation, leukocytic cell infiltration, and vacuolar degeneration in our study the model of NS rats was successfully established. Proteinuria is a hallmark of NS.…”

Section: Discussionmentioning

confidence: 62%

Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation

Wang¹,

Liu²,

Wang³

et al. 2023

DDDT

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Background: Nephrotic syndrome (NS) and its numerous complications remain the leading causes of morbidity and mortality globally. Sanqi Qushi granule (SQG) is clinically effective in NS. However, its potential mechanisms have yet to be elucidated. Methods: A network pharmacology approach was employed in this study. Based on oral bioavailability and drug-likeness, potential active ingredients were picked out. After acquiring overlapping targets for drug genes and disease-related genes, a component-targetdisease network and protein-protein interaction analysis (PPI) were constructed using Cytoscape, followed by GO and KEGG enrichment analyses. Adriamycin was injected into adult male Sprague-Dawley (SD) rats via the tail vein to establish NS model. Kidney histology, 24-hr urinary protein level, creatinine (Cr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) level were assessed. Western blotting, immunohistochemistry, and TUNEL staining were applied. Results: In total, 144 latent targets in SQG acting on NS were screened by a network pharmacology study, containing AKT, Bax, and Bcl-2. KEGG enrichment analysis suggested that PI3K/AKT pathway was enriched primarily. In vivo validation results revealed that SQG intervention ameliorated urine protein level and podocyte lesions in the NS model. Moreover, SQG therapy significantly inhibited renal cells apoptosis and decreased the ratio of Bax/Bcl-2 protein expression. Moreover, we found that Caspase-3 regulated the PI3K/AKT pathway in NS rats, which mediated the anti-apoptosis effect. Conclusion: By combining network pharmacology with experimental verification in vivo, this work confirmed the treatment efficacy of SQG for NS. SQG protected podocyte from injury and inhibited kidney apoptosis in NS rats via the PI3K/AKT pathway at least partially.

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Section: Discussionmentioning

confidence: 62%

Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation

Wang¹,

Liu²,

Wang³

et al. 2023

DDDT

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“…Adriamycin induced nephropathy model is similar to human nephropathy, characterized by abnormal thickening of glomerular basement membrane, glomerular sclerosis, and tubule interstitial inflammation 3,4 . Previous studies have shown that adriamycin injected into rodents rapidly distributes into kidney tissue and causes kidney damage, including podocyte damage, severe inflammation, and glomerulosclerosis 5,6 . In addition, the quinone structure of adriamycin can produce reactive oxygen species to induce peroxidation, destroy the integrity of the glomerular filtration membrane, and even lead to proteinuria 7,8 .…”

Section: Introductionmentioning

confidence: 99%

“… 3 , 4 Previous studies have shown that adriamycin injected into rodents rapidly distributes into kidney tissue and causes kidney damage, including podocyte damage, severe inflammation, and glomerulosclerosis. 5 , 6 In addition, the quinone structure of adriamycin can produce reactive oxygen species to induce peroxidation, destroy the integrity of the glomerular filtration membrane, and even lead to proteinuria. 7 , 8 Currently, glucocorticoids are the main treatment for adriamycin‐induced nephropathy; however, glucocorticoid treatment is frequently has serious side effects, and patients are prone to developing drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Epimedium sagittatum Maxim ameliorates adriamycin‐induced nephropathy by restraining inflammation and apoptosis via the PI3K/AKT signaling pathway

Wang,

Zeng,

Zhang

et al. 2023

Immunity Inflam & Disease

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Background: Modern pharmacological studies show that Epimedium sagittatum Maxim (EPI) has antioxidant, antiapoptotic, anti-inflammatory effects. However, the effects of EPI on adriamycin-induced nephropathy are unclear. Aim:The main purpose of this study is to investigate the effects of EPI on adriamycin-induced nephropathy in rats. Methods: The chemical composition of EPI was detected by high performance liquid chromatography. Network pharmacology was used to collect the effects of EPI on adriamycin nephropathy; renal histological changes, podocyte injury, inflammatory factors, oxidative stress levels, apoptosis levels, and the PI3K/AKT signaling pathway were examined. Moreover, analyze the effects of icariin (the representative component of EPI) on adriamycin-induced apoptosis and PI3K/AKT signaling pathway of NRK-52e cells. Results: Network pharmacological results suggested that EPI may ameliorate adriamycin-induced nephropathy by inhibiting inflammatory response and regulating the PI3K/AKT signaling pathway. The experimental results showed that EPI could improve pathological injury, renal function, podocyte injury, and inhibit inflammation, oxidative stress, apoptosis in adriamycin-induced nephropathy rats through the PI3K/AKT signaling pathway. Furthermore, icariin inhibited adriamycin-induced mitochondrial apoptosis in NRK-52e cells. Conclusion: This study suggested that EPI ameliorates adriamycin-induced nephropathy by reducing inflammation and apoptosis through the PI3K/AKT signaling pathway, icariin may be the pharmacodynamic substance basis for this effect.

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Tadalafil pretreatment attenuates doxorubicin-induced hepatorenal toxicity by modulating oxidative stress and inflammation in Wistar rats

Adeneye,

Babatope,

Adesiji-Adelekan

et al. 2024

Toxicology Reports

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Protective effects of tadalafil on damaged podocytes in an adriamycin-induced nephrotic syndrome model

Cited by 5 publications

References 43 publications

Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation

Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation

Epimedium sagittatum Maxim ameliorates adriamycin‐induced nephropathy by restraining inflammation and apoptosis via the PI3K/AKT signaling pathway

Tadalafil pretreatment attenuates doxorubicin-induced hepatorenal toxicity by modulating oxidative stress and inflammation in Wistar rats

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