Potential urinary biomarkers of nephrotoxicity in cyclophosphamide‐treated rats investigated by NMR‐based metabolic profiling

Lim, Sa Rang; Hyun, Sun Hee; Lee, Seul Gi; Kim, Jin Young; Kim, So Hyun; Park, Soo‐Jin; Moon, Kyoung-Sik; Sul, Donggeun; Kim, Dong Hyun; Choi, Hae-Jin

doi:10.1002/jbt.21871

Cited by 14 publications

(14 citation statements)

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“…Cyclophosphamide [CP], as a cytotoxic alkylating agent used in treatment cancers and as an immunosuppressive agent in organ transplantation and autoimmune diseases [1]. Despite its usefulness, its use due to undesirable effects, including nephrotoxicity, associated with restrictions [2]. Phosphoramide mustard and acrolein, as two of major metabolites of CP induce toxicity [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Generation of free radicals and oxidative stress is the main mechanism for inducing toxicity [3]. The side effects of CP in cancer patients are glomerular and tubular dysfunction, renal papillary necrosis and pyelonephritis [ 2 ] . In CP-induced nephrotoxicity increase plasma CREA [creatinine] and BUN [Blood Urea Nitrogen] levels, which indicates renal glomerular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice

Hamzeh¹,

Amiri²,

Beklar³

et al. 2018

mpj

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Cyclophosphamide [CP], as alkylating agents has side effects such as nephrotoxicity. Cerium oxide nanoparticles [nanoceria; NC], as an antioxidant, are effective at reduction oxidative stress. This study evaluated the protective effect of nanoceria in nephrotoxicity induced CP. 32 BALB/c mice were randomly divided into four equal groups. Control, NC, CP and NC+CP. NC and CP injected intraperitoneally respectively in dose of 100 μg/kg for 3 days and 200 mg/kg single dose on 3th day of study. Two days after the final treatment, histochemical, serum biochemical, histopathological and immunohistochemical examinations were performed for determination effects of NC on nephrotoxicity. Oxidative stress and renal injury induced in CP treated mice were proved by the significantly elevation of urea and creatinine and alteration in oxidative stress markers [MDA and GSH levels]. Consequently, histopathological changes and apoptosis were markedly increased. NC was able to reduce MDA, urea , creatinine and increase GSH content. In addition, NC pretreatment could alleviated immunoreactivity of caspase-3. NC revealed a strong antioxidant in nephrotoxicity following CP treatment. This study suggests that NC through antioxidant and antiapoptotic properties have protective effect against CP-induced nephrotoxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice

Hamzeh¹,

Amiri²,

Beklar³

et al. 2018

mpj

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“…This mixture was pipetted into a 5‐mm NMR tube. 1 H‐NMR analyses were performed according to the methods described in our previous report using a 600.13‐MHz Bruker Avance spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) (Lim et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Variables with VIP values >1 were selected as potentially discriminant. 1 H‐NMR data processing and analysis was performed as described previously (Lim et al, ).…”

Section: Methodsmentioning

confidence: 99%

Increased hepatic acylcarnitines after oral administration of amiodarone in rats

Kim

Choi

Lee

et al. 2020

J of Applied Toxicology

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Amiodarone is known to induce hepatic injury in some recipients. We applied an untargeted metabolomics approach to identify endogenous metabolites with potential as biomarkers for amiodarone-induced liver injury. Oral amiodarone administration for 1 week in rats resulted in significant elevation of acylcarnitines and phospholipids in the liver. Hepatic short-and medium-chain acylcarnitines were dramatically increased in a dose-dependent manner, while the serum levels of these acylcarnitines did not change substantially. In addition, glucose levels were significantly increased in both the serum and liver. Gene expression profiling showed that the hepatic mRNA levels of Cpt1, Cpt2, and Acat1 were significantly suppressed, whereas those of Acot1, Acly, Acss2, and Acsl3 were increased. These results suggest that hepatic acylcarnitines and glucose levels might be increased due to disruption of mitochondrial function and suppression of glucose metabolism. Perturbation of energy metabolism might be associated with amiodarone-induced hepatotoxicity. K E Y W O R D Sacylcarnitine, amiodarone, hepatotoxicity, LC/MSMS, metabolomics

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“…Using CP was restricted in spite of its effectiveness because of its organ toxicity as a result ofthe generation of free radicals and oxidative stress [4] .…”

Section: Introductionmentioning

confidence: 99%

The Protective Role of Atorvastatin against the Damage Induced by Cyclophosphamide on the Kidney and Testis of Adult Male Albino Rat: Histological, Biochemical and Histomorphmetric Study

Gadallah

2020

The Medical Journal of Cairo University

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Background: Cyclophosphamide (CP) is commonly used as chemotherapy for many cancers as well as autoimmune disorders. However, upon treatment, it was found that it had side effect which was the cause of histological and biochemical changes due to its oxidative stress capability. Atorvastatin (ATV) at a therapeutic low dose has been found to have antioxidant and anti-inflammatory properties. Aim of Study: The present work was designed to evaluate the adverse effect of cyclophosphamide on the histology and oxidative markers of the kidneys and testes of adult male albino rats. Moreover, the study evaluated the role of Atorvastatin in prevention and treatment of the possible renal and testicular histological and biochemical alterations induced by cyclophosphamide. Material and Methods: Twenty-four adult male albino rats were utilized in the present study, six in each group; Group I (control group), Group II receiving Cyclophosphmideonly, Group III receiving Atorvastatin 10 days after-Cyclophosphmide, Group IV receiving Atorvastatin 5 days before and 5 days after Cyclophosphmide. The kidneys and testes of all rats were dissected and removed for investigation using light microscopic study, biochemical analysis, histomorphometrical and statistical study. Results: Light microscopic examination of the renal cortex of the kidneys of group II showed shrunken renal glomeruli with subsequent widening of the Bowman's space, and interstitial inflammatory cellular infiltration. The proximal and distal convoluted tubules appeared dilated. Examination of the rat testes of group II displayed histological changes in theform of irregular distorted seminiferous tubules with marked degenerative changes of the spermatogenic epithelium. The interstitial spaces were wide containing pyknotic Leydig cells, dilated congested blood vessels and interstitial acidophilic exudate. The renal glomeruli and seminiferous tubules showed increased amount of collagen fibers deposition in the interstitial tissue in Masson's stained sections. Light microscopic examination of the kidneys and testes of group III and IV showed recovery of the histological changes.

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Potential urinary biomarkers of nephrotoxicity in cyclophosphamide‐treated rats investigated by NMR‐based metabolic profiling

Cited by 14 publications

References 36 publications

Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice

Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice

Increased hepatic acylcarnitines after oral administration of amiodarone in rats

The Protective Role of Atorvastatin against the Damage Induced by Cyclophosphamide on the Kidney and Testis of Adult Male Albino Rat: Histological, Biochemical and Histomorphmetric Study

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