Evaluation of urinary bladder fibrogenesis in mouse model of long-term ketamine injection

Shen, Cheng‐Huang; Wang, Shou‐Chieh; Wang, Shou-Tsung; Lin, Shumei; Wu, Jiann-Der; Lin, Chii-Jeng; Liu, Yiwen

doi:10.1016/j.urols.2016.05.286

Cited by 10 publications

(18 citation statements)

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“…179 A number of studies demonstrated that the subepithelial capillary network was significantly changed in the bladders of patients with KC. 10,153,154 However, little is known about the muscular network in the bladders of patients with KC, and further investigation is warranted. The subepithelial capillary network in the human bladder has been studied in detail by scanning electron microscopy, 180 it is located close to the urothelium and surrounded by urothelial cells.…”

Section: Microvascular Injury Initiate Bladder Dysfunctionmentioning

confidence: 99%

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

et al. 2021

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Section: Microvascular Injury Initiate Bladder Dysfunctionmentioning

confidence: 99%

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

et al. 2021

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“…Numerous animal studies have demontrated that long-term ketamine treatment can lead to bladder fibrosis, which is an important cause of bladder abnormalities, including decreased capacity, lower compliance and impaired detrusor function (41,42). Song et al (41) demonstrated that the inflammatory mediators in KIC increased the expression of collagen type-I (COL-I) and α-SMA, which leads to thickening of the bladder basement membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Song et al (41) demonstrated that the inflammatory mediators in KIC increased the expression of collagen type-I (COL-I) and α-SMA, which leads to thickening of the bladder basement membrane. Furthermore, Shen et al (42) conducted whole genome analysis and reported that the expression of fibrotic genes, including fibronectin, TGF-β1 and COL-I, were upregulated in bladder tissues with KIC. This enriched expression was considered to be a sensitive marker of active fibrosis development.…”

Section: Discussionmentioning

confidence: 99%

<em>Aldh2</em> gene reduces oxidative stress in the bladder by regulating the NF‑κB pathway in a mouse model of ketamine‑induced cystitis

Chen

2020

Exp Ther Med

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Aldehyde dehydrogenase 2 (aldh2) serves an important role in the development of organ injury. Therefore, the present study investigated the effects of aldh2 on the oxidative stress response in a mouse model of ketamine-induced cystitis (KIC). A total of 60 8-week-old male Institute of Cancer Research wild-type (WT) mice and 45 aldh2 knock-out (KO) mice were randomized to receive low-dose ketamine (30 mg/kg), high-dose ketamine (60 mg/kg) or normal saline (controls). At 4, 8 and 12 weeks post-injection, bladder tissues were harvested and used to investigate the protective mechanisms of aldh2 on bladder function. The results demonstrated that aldh2 KO mice exhibited significant weight loss following chronic ketamine injection compared with that in WT mice. Furthermore, ketamine treatment increased the urination rate (P<0.05), pathological score (P<0.05), levels of the oxidative stress product malondialdehyde (P<0.05) in addition to reducing the expression of the anti-oxidative stress enzyme superoxide dismutase (P<0.05) and glutathione-SH (P<0.05). Oxidative stress in aldh2 KO mice was also found to significantly enhance the expression of proteins associated with the NF-κB signaling pathway, which promoted the expression of inducible nitric oxide synthase (P<0.05) and cyclooxygenase-2 (P<0.05) further. Finally, aldh2 KO mice demonstrated higher severity of fibrosis in the submucosal and muscular layers of the bladder. In conclusion, the present study suggests that aldh2 serves a protective role in preventing inflammation and fibrosis in KIC.

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“…Therefore, the bladder inflammation appears to be produced through the T‐helper cells pathway, promoting interleukin production which causes tissue destruction and fibrosis 29 . Fibrosis due to collagen deposit develops (in mice) at an early stage of the disease and is correlated to overexpression of transforming growth factor β1 and fibronectin, and activation of the mammalian target of the rapamycin 30,31 . The subsequent epithelial‐to‐mesenchymal transition determines impaired bladder contractility 32 .…”

Section: Evidencementioning

confidence: 99%

What urologists need to know about ketamine‐induced uropathy: A systematic review

Castellani

Pirola

Gubbiotti

et al. 2020

Neurourology and Urodynamics

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Aims: Ketamine is a general anesthetic. Dissociative effects and low cost led ketamine becoming an illegal recreational drug in young adults. Ketamineinduced uropathy (KIU) is one of the complications observed in abusers. This study aimed to provide a systematic literature review on KIU clinical presentation, pathophysiology, and treatments. Methods: We performed the literature search in PubMed, Web of Science, Scopus, and Embase using the terms ketamine and bladder. English papers on human and animal studies were accepted. Results: A total of 75 papers were selected. Regular ketamine users complain about severe storage symptoms and pelvic pain. Hydronephrosis may develop in long-term abusers and is correlated to the contracted bladder, ureteral stenosis, or vesicoureteral reflux due to ureteral involvement and/or bladder fibrosis. Cystoscopy shows ulcerative cystitis. Ketamine in urine might exert direct toxicity to the urothelium, disrupting its barrier function and enhancing cell apoptosis. The presence of ketamine/ions in the bladder wall result in neurogenic/IgE-mediated inflammation, stimulation of the inducible nitric oxide synthase-cytokines-cyclooxygenase pathway with persistent inflammation and fibrosis. Abstinence is the first therapeutic step. Anti-inflammatory drugs, analgesics and anticholinergics, intravesical instillation of hyaluronic acid, hydrodistension and intravesical injection of botulin toxin-A were helpful in patients with early-stage KIU. In patients with end-stage disease, the control of intractable symptoms and the increase of bladder capacity were the main recommendations to perform augmentation enterocystoplasty.Conclusions: KIU is becoming a worldwide health concern, which should be taken into account in the differential diagnosis of ulcerative cystitis. K E Y W O R D S cystitis, inflammation, ketamine, lower urinary tract symptoms, substance-related disorders, urinary tract 1050 | CASTELLANI ET AL.

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Evaluation of urinary bladder fibrogenesis in mouse model of long-term ketamine injection

Cited by 10 publications

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Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

<em>Aldh2</em> gene reduces oxidative stress in the bladder by regulating the NF‑κB pathway in a mouse model of ketamine‑induced cystitis

What urologists need to know about ketamine‐induced uropathy: A systematic review

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Evaluation of urinary bladder fibrogenesis in mouse model of long-term ketamine injection

Cited by 10 publications

References 0 publications

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis

<em>Aldh2</em> gene reduces oxidative stress in the bladder by regulating the NF‑&kappa;B pathway in a mouse model of ketamine‑induced cystitis

What urologists need to know about ketamine‐induced uropathy: A systematic review

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<em>Aldh2</em> gene reduces oxidative stress in the bladder by regulating the NF‑κB pathway in a mouse model of ketamine‑induced cystitis