Protective Effect of Intravesical Platelet-Rich Plasma on Cyclophosphamide-Induced Hemorrhagic Cystitis

Ozyuvali, E; Yildirim, ME; Yaman, T; Kosem, B; Cimentepe, E

doi:10.25011/cim.v39i6.27524

Cited by 5 publications

(6 citation statements)

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“…Candidate drugs targeting the inflammatory IL-1 β , TNF α and IL-6 triad 18,23 and/or promoting antioxidant responses show promise for ameliorating hemorrhagic cystitis but have not progressed beyond preclinical testing. Most efforts have been focused towards finding alternatives to MESNA, including anti-inflammatory molecules 24–26 , hemostatic agents 27,28 , antioxidants 29–31 , cytokines 12,32 , platelet rich plasma 33 , nutritional approaches 34 , and plant extracts 26,35 . These early-stage therapeutic candidates target pro-inflammatory pathways, heme homeostasis pathway and anti-oxidant homoeostasis.…”

Section: Introductionmentioning

confidence: 99%

IPSE, a urogenital parasite-derived immunomodulatory protein, ameliorates ifosfamide-induced hemorrhagic cystitis through downregulation of pro-inflammatory pathways

Mbanefo

Zee

et al. 2019

Sci Rep

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Ifosfamide and other oxazaphosphorines can result in hemorrhagic cystitis, a constellation of complications caused by acrolein metabolites. We previously showed that a single dose of IPSE (Interleukin-4-inducing principle from Schistosoma eggs), a schistosome-derived host modulatory protein, can ameliorate ifosfamide-related cystitis; however, the mechanisms underlying this urotoxicity and its prevention are not fully understood. To provide insights into IPSE’s protective mechanism, we undertook transcriptional profiling of bladders from ifosfamide-treated mice, with or without pretreatment with IPSE or IPSE-NLS (a mutant of IPSE lacking nuclear localization sequence). Ifosfamide treatment upregulated a range of proinflammatory genes. The IL-1β-TNFα-IL-6 proinflammatory cascade via NFκB and STAT3 pathways was identified as the key driver of inflammation. The NRF2-mediated oxidative stress response pathway, which regulates heme homoeostasis and expression of antioxidant enzymes, was highly activated. Anti-inflammatory cascades, namely Wnt, Hedgehog and PPAR pathways, were downregulated. IPSE drove significant downregulation of major proinflammatory pathways including the IL-1β-TNFα-IL-6 pathways, interferon signaling, and reduction in oxidative stress. IPSE-NLS reduced inflammation but not oxidative stress. Taken together, we have identified signatures of acute-phase inflammation and oxidative stress in ifosfamide-injured bladder, which are reversed by pretreatment with IPSE. This work revealed several pathways that could be therapeutically targeted to prevent ifosfamide-induced hemorrhagic cystitis.

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Section: Introductionmentioning

confidence: 99%

IPSE, a urogenital parasite-derived immunomodulatory protein, ameliorates ifosfamide-induced hemorrhagic cystitis through downregulation of pro-inflammatory pathways

Mbanefo

Zee

et al. 2019

Sci Rep

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“…In IC/BPS patients uVEGF was reduced by the third PRP intravesicular injection 13 . Intravesical PRP instillation has been shown to reduce bladder bleeding in a rat model of hemorrhage induced by cyclophosphamide 147 .…”

Section: Prp and Growth Factors Related Genesmentioning

confidence: 99%

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model

Abdelgalil,

Yassin,

Khattab

et al. 2024

Sci Rep

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One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.

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“…23 However, further histological assessment after a single PRP instillation did not find significant changes in cystitis bladder walls in rats. 24 In a recent study on the therapeutic effects of combined PRP and hyaluronic acid on normal human fibroblast cell proliferation, low PRP doses increased cell proliferation. 25 In cyclophosphamide-treated acute cystitis rat model simulating IC/BPS, the cyclophosphamide plus intravesical PRP instillation group had significantly higher voiding interval values.…”

Section: Prp Treatment For Bladder Inflammatory Conditionsmentioning

confidence: 99%

“…PRP‐treated bladders exhibit significantly reduced hemorrhage, increased leukocyte infiltration, and increased proliferation indexes, suggesting that PRP intravesical instillation improves urothelial cell proliferation and repairs urothelial deficiency in chemically induced cystitis 23 . However, further histological assessment after a single PRP instillation did not find significant changes in cystitis bladder walls in rats 24 . In a recent study on the therapeutic effects of combined PRP and hyaluronic acid on normal human fibroblast cell proliferation, low PRP doses increased cell proliferation 25 .…”

Section: Prp Treatment For Bladder Inflammatory Conditionsmentioning

confidence: 99%

Intravesical injections of autologousplatelet‐richplasma for the treatment of refractory interstitial cystitis

Kuo

2023

LUTS

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The urothelium acts as a barrier for the urinary bladder that prevents the influx of urinary toxic substances, electrolytes, urea nitrogen, and pathogens into the circulation. Acute or chronic inflammation of the urinary bladder may impair the regenerative function of urothelial cells and thus urothelial cell differentiation. In an inflamed bladder wall, mature apical cells are defective, resulting in impaired barrier function and thus increased urothelial permeability. This is considered to be the potential mechanism of the symptom trigger in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Previous studies have revealed that increased bladder inflammation, impaired urothelial cell maturation, a defective umbrella cell barrier, and defective junction proteins are prominent in IC/BPS bladders. Platelet‐rich plasma (PRP) contains many growth factors and cytokines that are essential proteins for modulating inflammation and promoting tissue regeneration and thus wound healing. As such, PRP has been used as a regenerative therapy in many medical fields. Our preliminary studies have demonstrated that multiple intravesical PRP injections could improve symptoms in 70% of IC/BPS patients. Repeated PRP treatments also improve junctional protein, increase cytoskeleton protein expression, and decrease urinary inflammatory proteins. These preliminary results suggest that PRP injections might reduce bladder inflammation and improve urothelial cell regeneration in IC/BPS patients. This article reviews recently published clinical and basic research on the treatment potential of PRP for IC/BPS patients.

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Protective Effect of Intravesical Platelet-Rich Plasma on Cyclophosphamide-Induced Hemorrhagic Cystitis

Cited by 5 publications

References 0 publications

IPSE, a urogenital parasite-derived immunomodulatory protein, ameliorates ifosfamide-induced hemorrhagic cystitis through downregulation of pro-inflammatory pathways

IPSE, a urogenital parasite-derived immunomodulatory protein, ameliorates ifosfamide-induced hemorrhagic cystitis through downregulation of pro-inflammatory pathways

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model

Intravesical injections of autologousplatelet‐richplasma for the treatment of refractory interstitial cystitis

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