Protective Effects of Boron on Cyclophosphamide-Induced Bladder Damage and Oxidative Stress in Rats

Ayhancı, Adnan; Tanriverdi, Dondu Tugce; Şahıntürk, Varol; Cengiz, Mustafa; Appak-Baskoy, Sıla; Şahin, İlknur Kulcanay

doi:10.1007/s12011-019-01969-z

Cited by 35 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptosis has a great impact on the pathogenesis of CYP-induced urinary injury (Kim et al, 2014). Apoptosis was confirmed following CYP in the bladder tissue via a marked rise in the caspase-3 positive cells (Ayhanci et al, 2019;Kim et al, 2014).…”

Section: Effects Of Cypmentioning

confidence: 98%

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review

Sherif

2020

Acta Sci Pol Technol Aliment

View full text Add to dashboard Cite

One of the widely used anticancer drugs for the treatment of various neoplasms is cyclophosphamide (CYP). The inactive prodrug CYP is metabolized by cytochrome P450 enzyme into active metabolites, phosphoramide mustard and acrolein. The accumulation of acrolein metabolite inside the urothelium results in hemorrhagic cystitis (HC) which is a urotoxic adverse effect associated with the use of CYP. To counteract the occurrence of HC induced by CYP, Mesna is usually used, with allergic reactions reported in some cases. Therefore, several natural products have drawn much attention as alternative safe therapies to reduce the urotoxicity produced from the use of CYP. This review will focus on certain uroprotective mechanisms related to some medicinal plants that are used to ameliorate the CYP-induced urotoxicity in experimental models. The mechanisms involving oxidative stress, inflammation, immune system, apoptosis, DNA fragmentation, uroplakins, purinergic signaling and muscarinic receptors, and CytoP450 metabolism are discussed.

show abstract

Section: Effects Of Cypmentioning

confidence: 98%

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review

Sherif

2020

Acta Sci Pol Technol Aliment

View full text Add to dashboard Cite

show abstract

“…Apoptosis is the key mechanism of CYP-induced bladder toxicity [ 39 ], which can be triggered by inflammatory factors and oxidative stress [ 40 ]. Chronic intermittent hypoxia-induced mitochondrial dysfunction mediates endothelial injury via the TXNIP/NLRP3/IL-1 β pathway.…”

Section: Discussionmentioning

confidence: 99%

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Zhang

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-κB pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-κB signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-κB pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.

show abstract

“…15 Group III (cyclophosphamide group): the rats received 0.9% saline injection through intraperitoneal injection for consecutive 5 days and a single dose of cyclophosphamide (200 mg/kg) on the six day. 16 Group IV (Sulforaphane and cyclophosphamide): the rats received sulforaphane at a dose of 5 mg/kg for consecutive 5 days and a single dose of cyclophosphamide 200 mg/kg on the six day. On the seventh day of experiment, the animals were sacrificed under anesthesia and urinary bladder samples were dissected for histopathological, immunohistochemical investigations and electron microscopic studies.…”

Section: Experimental Designmentioning

confidence: 99%

“…Stained tissue sections were examined under light microscope at 20X magnification. 16 For immunohistochemistry (IHC) staining, the sections were dewaxed (xylene, 4×3 min), rehydrated (100% ethanol, 4×1 min, 70% ethanol, 1 min, distilled water, 3×1 min), and then heat-induced antigen retrieval was used as previously reported. 17 Then endogenous peroxidase was blocked with 3% hydrogen peroxide at room temperature (10 min), and sections were washed with distilled water (2×5 min) and PBS (5 min).…”

Section: Histopathological Investigation and Immunohistochemical Studymentioning

confidence: 99%

“…38 In addition, Ayhanci et al detected high caspase-3 levels in transient epithelium of the bladder treated with cyclophosphamide. 16 This cellular necrosis may be due to protein denaturation, oxidative DNA damage through changes of mitochondrial membrane potential, release of cytochrome C, and activation of the caspase cascade. 37 TEM of urinary bladder mucosa in cyclophosphamide treated group showed degenerated swollen intermediate cells with dilation and loss of many cytoplasmic organelles.…”

Section: C2 C3 Dmentioning

confidence: 99%

See 1 more Smart Citation

Acute effect of cyclophosphamide on rat’s urinary bladder and the possible protective role of sulforaphane: a histological and ultrastructural study

et al. 2021

View full text Add to dashboard Cite

Background: Cyclophosphamide disturbs the oxidant and antioxidant balance that is associated with several unwanted toxic effects and induction of secondary cancers. The aim of this study was to test the protective effects of Sulforaphane on the cyclophosphamide toxicity of rat urinary bladder.Methods: 32 male albino rats were divided into 4 groups, 8 animal each (n=8). Group I received saline intra-peritoneal, group II received 5 mg/kg sulforaphane for 5 days and then saline, group III received 0.9% saline intra-peritoneal for consecutive 5 days and a single dose of cyclophosphamide 200 mg/kg on the six-day, group IV received sulforaphane at a dose of 5 mg/kg for consecutive 5 days and a single dose of cyclophosphamide 200 mg/kg on the six day. On the seventh day of the experiment, the animals were sacrificed, and the urinary bladder samples were dissected for histopathological and immunohistochemical investigations and electron microscopic studies.Results: the mucosa of the urinary bladder of Sulforaphane treated group showed normal architecture while that of cyclophosphamides treated group showed features of degenerated and ulcerated lesions of the epithelial lining associated with hemorrhage. Theses lesions markedly decreased in the mucosa of urinary bladder of cyclophosphamides and sulforaphane treated group.Conclusions: The use of sulforaphane reduces the cyclophosphamide toxicity on the urinary bladder in the form of decreased vacuolation with decreased degeneration of the epithelial lining.

show abstract

Protective Effects of Boron on Cyclophosphamide-Induced Bladder Damage and Oxidative Stress in Rats

Cited by 35 publications

References 32 publications

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Acute effect of cyclophosphamide on rat’s urinary bladder and the possible protective role of sulforaphane: a histological and ultrastructural study

Contact Info

Product

Resources

About