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Извлечено: 997 / 997 (100.0%) Средняя confidence: 0.13
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Plant-Derived Spinacetin Mitigates Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

PMID: 41977243 · DOI: 10.3390/ijms27073056 · International journal of molecular sciences, 2026 · Jan Wróbel, Łukasz Zapała, Grzegorz Niemczyk, Anna Bogaczyk, Tomasz Kluz, Artur Wdowiak, Aleksandra Misiek, Iwona Bojar,
📄 Abstract

The purpose of our study was to assess if spinacetin (SPC), a flavonoid found in spinach, can alleviate the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters indicative of the development of hemorrhagic cystitis. The animal experiments were conducted in female Wistar rats. The cohort of 60 animals was grouped as follows: I-control, II-CYP group, III-SPC group, and IV-CYP + SPC group. The cystometry and biochemical analyses were performed after a fortnight of SPC administration. SPC was found to restore normal cystometric parameters in CYP-induced cystitis and, similarly, it normalized c-Fos expression changes in the central micturition regions. SPC further prevented a massive increase in the bladder wall thickness/permeability due to exposition to CYP administration. CYP instillation resulted in the elevation of biomarkers found in urine (brain-derived neurotrophic factor, BDNF, and nerve growth factor, NGF), and in the bladder detrusor muscle (Rho kinase and vesicular acetylcholine transporter, VAChT), which were successfully restored after administration of SPC. As for the biomarkers in the bladder urothelium, the CYP-induced increases in TNF-α, IL-1β, IL-6, calcitonin gene-related peptide (CGRP), malondialdehyde, 3-nitrotyrosine, insulin-like growth factor-binding protein 3 (IGFBP-3), occludin, organic cation transporter 3 (OCT-3), orosomucoid-1 (ORM1), pituitary adenylate cyclase receptor 1 (PAC1), synaptosomal-associated protein 23 (SNAP23), SNAP25, and synaptic vesicle glycoprotein (SV2A) levels were attenuated by SPC. Finally, CYP administration resulted in a decrease in the heparin-binding EGF-like growth factor (HB-EGF), hemopexin (HPX), T-H protein, and tight junction protein (Z01), and we noted the successful restoration of all these changes in concentrations after application of SPC. In summary, SPC robustly mitigated cyclophosphamide (CYP)-induced cystometric dysfunction and biochemical alterations characteristic of iatrogenic hemorrhagic cystitis. These findings position SPC as a compelling therapeutic candidate and warrant further translational investigation for the management of CYP-induced bladder injury.

Confidence: 0.21 · 10 полей извлечено
Идентификация (6 полей)
Target
Spinacetin
1.00
Alt. target
SPC
1.00
Protein family
Flavonoid
1.00
Functional class
0.00
Subcellular loc.
0.00
Isoforms (metab/obesity)
0.00
Механизм действия (21 полей)
Mechanism
0.00
Mutations (obesity/lean)
0.00
Activity (obesity)
0.00
Activity temporal
0.00
Energy balance
0.00
Appetite
0.00
Fat metabolism
0.00
Lipolysis
0.00
Thermogenesis
0.00
Muscle metabolism
0.00
Inflammation
0.00
Glucose metabolism
0.00
AA metabolism
0.00
Hormonal pathways
0.00
Cell death
0.00
Adipocyte fibrosis
0.00
Upstream (biochem)
0.00
Upstream (physiol)
0.00
Downstream (biochem)
0.00
Downstream (physiol)
0.00
PTMs
0.00
Экспрессия (8 полей)
Tissue expression
0.00
In vitro
0.00
In vivo
Spinacetin was administered to female Wistar rats with cyclophosphamide-induced hemorrhagic cystitis. Cystometry and biochemical analyses were performed after two weeks of spinacetin administration. Spinacetin restored normal cystometric parameters, normalized c-Fos expression in central micturition regions, prevented bladder wall thickening and permeability increase, and attenuated changes in various urinary and bladder biomarkers (BDNF, NGF, Rho kinase, VAChT, TNF-α, IL-1β, IL-6, CGRP, malondialdehyde, 3-nitrotyrosine, IGFBP-3, occludin, OCT-3, ORM1, PAC1, SNAP23, SNAP25, SV2A, HB-EGF, HPX, T-H protein, ZO1).
0.95
In silico
0.00
Genetic association
0.00
Ex vivo
0.00
Animal model
Female Wistar rats
0.95
Diet/model
Cyclophosphamide-induced hemorrhagic cystitis model
0.95
Клиника (11 полей)
Drug
spinacetin
1.00
Indication
cyclophosphamide-induced hemorrhagic cystitis
1.00
Patient subgroups
0.00
Safety concerns
0.00
Off-target
0.00
Trial stage
preclinical
0.90
Pharma competitors
0.00
AE severity
0.00
MOA weight loss
0.00
Endpoints
0.00
Approved
False
1.00