Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: chloroacetaldehyde’s contribution to urothelial dysfunction in vitro

Mills, Kylie; Chess-Williams, Russ; McDermott, Catherine

doi:10.1007/s00204-019-02589-1

Cited by 59 publications

(40 citation statements)

References 55 publications

(62 reference statements)

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“…Cyclophosphamide is known to have cardiotoxicity which may be mitigated by NAC [ 83 ] and cyclophosphamide may cause hemorrhagic cystitis which may be prevented with NAC [ 84 ]. Acute kidney damage as seen with cisplatin may be reduced as seen in animal studies [ 85 ].…”

Section: Metabolic Syndrome Including Nonalcoholic Fatty Liver Disease Diabetes and Polycystic Ovarymentioning

confidence: 99%

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

Schwalfenberg

2021

Journal of Nutrition and Metabolism

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Objective. To review the clinical usefulness of N-acetylcysteine (NAC) as treatment or adjunctive therapy in a number of medical conditions. Use in Tylenol overdose, cystic fibrosis, and chronic obstructive lung disease has been well documented, but there is emerging evidence many other conditions would benefit from this safe, simple, and inexpensive intervention. Quality of Evidence. PubMed, several books, and conference proceedings were searched for articles on NAC and health conditions listed above reviewing supportive evidence. This study uses a traditional integrated review format, and clinically relevant information is assessed using the American Family Physician Evidence-Based Medicine Toolkit. A table summarizing the potential mechanisms of action for N-acetylcysteine in these conditions is presented. Main Message. N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases. These conditions include polycystic ovary disease, male infertility, sleep apnea, acquired immune deficiency syndrome, influenza, parkinsonism, multiple sclerosis, peripheral neuropathy, stroke outcomes, diabetic neuropathy, Crohn’s disease, ulcerative colitis, schizophrenia, bipolar illness, and obsessive compulsive disorder; it can also be useful as a chelator for heavy metals and nanoparticles. There are also a number of other conditions that may show benefit; however, the evidence is not as robust. Conclusion. The use of N-acetylcysteine should be considered in a number of conditions as our population ages and levels of glutathione drop. Supplementation may contribute to reducing morbidity and mortality in some chronic conditions as outlined in the article.

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Section: Metabolic Syndrome Including Nonalcoholic Fatty Liver Disease Diabetes and Polycystic Ovarymentioning

confidence: 99%

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

Schwalfenberg

2021

Journal of Nutrition and Metabolism

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“…Unfortunately, alkylating agents do not differentiate between cancerous cells and normal cells. Common side effects for patients taking MPH and CYT include low blood counts, nausea, vomiting, and hair loss, to name a few [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan

Salazar

Yutronic

Kogan

et al. 2021

IJMS

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This article describes the synthesis and characterization of β-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV–Vis, and proton nuclear magnetic resonance (1H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV–Vis. Drug release studies using NSs synthesized with different molar ratios of β-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible.

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“…CPO is used in patients to treat a number of conditions, but urinary adverse effects are common due to metabolites such as acrolein and chloroacetaldehyde (CAA), which irritate the bladder (Mills et al, 2019). For this reason, the drug is also commonly used in animals as a model of bladder inflammation.…”

Section: Discussionmentioning

confidence: 99%

Hypersensitivity of bladder low threshold, wide dynamic range, afferent fibres following treatment with the chemotherapeutic drugs cyclophosphamide and ifosfamide

et al. 2020

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The cytotoxic drugs cyclophosphamide (CPO) and ifosfamide (IFO) cause toxic urological effects due to the production of urinary metabolites that cause bladder inflammation. This study aimed to identify changes in the bladder afferent system following treatment with these drugs that might explain reported urological adverse effects.Intravesical pressure and afferent nerve activity were recorded during bladder distension and drug administration in isolated bladders from mice, 24 hours after intraperitoneal treatment with cyclophosphamide (100mg/Kg), ifosphamide (200mg/Kg) or saline (control).In isolated bladders, total afferent nerve activity at maximum bladder distension was increased from 182±13 imp/sec in control animals, to 230±14 imp/sec in CPO-treated (p<0.05) and 226±17 imp/sec in IFO-treated (P<0.001) mice. Single fibre analysis revealed the increase resulted from an enhanced activity in low threshold, wide dynamic range fibres (23.3±1.9 imp/sec/fibre in controls to 31.5±2.5 (p<0.01) in CPO and 29.9±2.0 imp/sec/fibre (p<0.05) in IFO treated). CPO treatment was accompanied by an increase in urinary frequency in vivo, but was not associated with increases in urothelial release of ATP or acetylcholine, bladder compliance or spontaneous muscle activity. Also,CPOtreatment did not affect afferent nerve responses or pressure responses to purinergic, muscarinic or nicotinic agonists. This is the first report of CPO and IFO-induced changes in specific populations of bladder afferents, namely an increase in low threshold, wide dynamic range fibres. These effects appear to be direct and not secondary to increases in smooth muscle activity or the release of urothelial mediators.

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Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: chloroacetaldehyde’s contribution to urothelial dysfunction in vitro

Cited by 59 publications

References 55 publications

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan

Hypersensitivity of bladder low threshold, wide dynamic range, afferent fibres following treatment with the chemotherapeutic drugs cyclophosphamide and ifosfamide

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