Nilotinib ameliorates folic acid-induced acute kidney injury through modulation of TWEAK and HSP-70 pathways

Zaghloul,; Abdelrahman, Rehab S.

doi:10.1016/j.tox.2019.152303

Cited by 17 publications

(22 citation statements)

References 54 publications

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“…Earlier studies stated the implication of oxidative strain in FA‐induced AKI. [ 3,6,22 ] These findings agreed with the results of this study, which revealed a substantial elevation in levels of MDA and a profound decrease in GSH and SOD levels following FA injection. Oral administration of nicorandil in both doses effectively counteracted the deleterious impacts of FA‐induced oxidative stress.…”

Section: Discussionsupporting

confidence: 90%

“…The duration of treatment was selected based on a previous study that investigated the role of nilotinib against FA‐induced acute kidney injury. [ 3 ] On Day 9, all animals were retained in metabolic cages for 24 h for collecting urine samples. After that, these samples were centrifuged, and supernatants were kept for further analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Diagnosis of AKI can be confirmed by increased levels of creatinine (Cr) or blood urea nitrogen (BUN) in serum. [ 3 ]…”

Section: Introductionmentioning

confidence: 99%

“…[ 1 ] Previous studies reported an increase in the expression of Bax in renal tissues of FA‐injected animals. [ 1,3 ]…”

Section: Introductionmentioning

confidence: 99%

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Nicorandil mitigates folic acid‐induced nephrotoxicity in mice: Role of iNOS and eNOS

Ezzat

Soliman

El‐Kashef

2021

J Biochem & Molecular Tox

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Folic acid (FA)‐induced acute kidney injury (AKI) is a commonly used model in experimental animals for studying renal injury. This study aimed to investigate the probable protecting impact of nicorandil against FA‐induced renal dysfunction. A mouse model was executed by a single injection of FA (250 mg/kg). Nicorandil was orally administrated in two doses (50 and 100 mg/kg) for 10 days. Nicorandil repressed the progression of FA‐induced AKI as evidenced by the improvement of histopathological alterations and the substantial decrease of serum levels of creatinine, urea, blood urea nitrogen, malondialdehyde (MDA), and urinary protein levels. Moreover, nicorandil resulted in a profound reduction in oxidative stress as manifested by decreased MDA and increased reduced glutathione and superoxide dismutase in renal tissue. Notably, nicorandil suppressed FA‐induced inflammation; it reduced renal levels of nuclear factor‐κB, tumor necrosis factor‐α, and interleukin‐6. Furthermore, nicorandil decreased renal levels of nitric oxide, inducible nitric oxide synthase, and increased endothelial nitric oxide synthase. Lastly, nicorandil efficiently decreased expression of the proapoptotic protein (Bax) and caspase 3. Nicorandil confers dose‐dependent protection against FA‐induced AKI by alleviating oxidative stress, inflammation besides modulating nitric oxide synthase and reducing apoptosis.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

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Nicorandil mitigates folic acid‐induced nephrotoxicity in mice: Role of iNOS and eNOS

Ezzat

Soliman

El‐Kashef

2021

J Biochem & Molecular Tox

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“…23 The severity of staining was graded semi-quantitatively and each sample was assigned a score according to. 24,25…”

Section: Methodsmentioning

confidence: 99%

Vinpocetine attenuates thioacetamide-induced liver fibrosis in rats

et al. 2020

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Liver fibrosis is associated with increased mortality and morbidity. However, there is not effective treatment so far. Vinpocetine (Vinpo) is a synthetic derivative of vinca alkaloid vincamine. Limited previous reports have shown some beneficial effects of Vinpo in different organ fibrosis, but the ability of Vinpo to inhibit liver fibrosis induced by thioacetamide (TAA) has not been reported, that is why we investigate the potential ability of this vinca alkaloid derivative to attenuate liver fibrosis. Hepatic fibrosis was induced in male Sprague Dawley rats by TAA (200 mg/kg; ip; 3 times/week) for 6 weeks. Daily treatments with Vinpo (10–20 mg/kg/day; orally) ameliorated TAA-induced hepatic oxidative stress and histopathological damage as indicated by a decrease in liver injury markers, LDH, hepatic MDA, and NOx levels, as well as increase anti-oxidative parameters. Besides, the anti-fibrotic efficacy of Vinpo was confirmed by decreasing hydroxyproline, and α-SMA. Also, the anti-inflammatory effect of Vinpo was explored by decreasing IL-6 and TNF-α levels. Our novel findings were that Vinpo decreased VEGF/Ki-67 expression in the liver confirming its effect on angiogenesis and proliferation. These findings reveal the anti-fibrotic effect of Vinpo against TAA-induced liver fibrosis in rats, and suggest the modulation of oxidative stress, inflammation, angiogenesis and proliferation as mechanistic cassette underlines this effect.

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Chloroquine Intervenes Nephrotoxicity of Nilotinib through Deubiquitinase USP13‐Mediated Stabilization of Bcl‐XL

et al. 2023

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Nephrotoxicity has become prominent due to the increase in the clinical use of nilotinib, a second‐generation BCR‐ABL1 inhibitor in the first‐line treatment of Philadelphia chromosome‐positive chronic myeloid leukemia. To date, the mechanism of nilotinib nephrotoxicity is still unknown, leading to a lack of clinical intervention strategies. Here, it is found that nilotinib could induce glomerular atrophy, renal tubular degeneration, and kidney fibrosis in an animal model. Mechanistically, nilotinib induces intrinsic apoptosis by specifically reducing the level of BCL2 like 1 (Bcl‐XL) in both vascular endothelial cells and renal tubular epithelial cells, as well as in vivo. It is confirmed that chloroquine (CQ) intervenes with nilotinib‐induced apoptosis and improves mitochondrial integrity, reactive oxygen species accumulation, and DNA damage by reversing the decreased Bcl‐XL. The intervention effect is dependent on the alleviation of the nilotinib‐induced reduction in ubiquitin specific peptidase 13 (USP13) and does not rely on autophagy inhibition. Additionally, it is found that USP13 abrogates cell apoptosis by preventing excessive ubiquitin‒proteasome degradation of Bcl‐XL. In conclusion, the research reveals the molecular mechanism of nilotinib's nephrotoxicity, highlighting USP13 as an important regulator of Bcl‐XL stability in determining cell fate, and provides CQ analogs as a clinical intervention strategy for nilotinib's nephrotoxicity.

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Nilotinib ameliorates folic acid-induced acute kidney injury through modulation of TWEAK and HSP-70 pathways

Cited by 17 publications

References 54 publications

Nicorandil mitigates folic acid‐induced nephrotoxicity in mice: Role of iNOS and eNOS

Nicorandil mitigates folic acid‐induced nephrotoxicity in mice: Role of iNOS and eNOS

Vinpocetine attenuates thioacetamide-induced liver fibrosis in rats

Chloroquine Intervenes Nephrotoxicity of Nilotinib through Deubiquitinase USP13‐Mediated Stabilization of Bcl‐XL

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