Cytosine arabinoside induced liver damage: Histopathologic demonstration

Pizzuto, J; Avilés, Agustín; Ramos, Ernesto; Cervera, J; Aguirre, Jesús María

doi:10.1002/mpo.2950110416

Cited by 20 publications

(6 citation statements)

References 11 publications

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“…the obtained results came in agreement with that obtained by Herzig et al (1983), who studied cytosine arabinoside therapy for refractory leukemia (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed. Another similar result was obtained by Pizzuto et al (1983) who, reported that cytosine arabinoside induced liver damage. Two patients with acute leukemia developed abnormal liver function tests after the administration of cytosine.…”

Section: Discussionsupporting

confidence: 84%

Some adverse effects of cytarabine in leukemic rats

El-Sayed

Farag

Khaled³

2016

Benha Veterinary Medical Journal

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In the present work, the biochemical and hematological parameters as well as histological changes following intravenous injection of 2 mg/ kg for 7 days and 3 mg cytarabine for 5 days in both normal and leukemic rats were studied. Sample were taken in the first, second and third week after end of administration of cytarabine. Both normal and leukemic rats showed significant increase in serum total bilirubin, AST, ALT, ALP, total protein and albumin after intravenous administration of cytarabine either 2 mg/kg body weight for 7 days or 3 mg/kg body weight for 5 days. The effect of intravenous injection of cytarabine either 2 mg/kg body weight for 7 days or 3 mg/kg body weight for 5 days on serum creatinine level in normal and leukemic rats showed a significant changes of kidney function through estimation of serum creatinine, urea and creatine kinase level. Intravenous injection of cytarabine either 2 mg/kg body weight for 7 days or 3 mg /kg body weight for 5 days induce significant increase on lipid profile (cholesterol and triglyceride) and MDA concentration in normal and leukemic rats.

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Section: Discussionsupporting

confidence: 84%

Some adverse effects of cytarabine in leukemic rats

El-Sayed

Farag

Khaled³

2016

Benha Veterinary Medical Journal

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“… 10 Nevertheless, there are reports of severe drug-induced hepatic cholestasis related to cytarabine therapy. 11 …”

Section: Specific Chemotherapymentioning

confidence: 99%

Hepatotoxicity Secondary to Chemotherapy

Grigorian

O’Brien

2014

JCTH

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The difficult problem faced by multiple generation of practicing physicians is determining the cause of abnormal liver function tests in cancer patients on chemotherapy. Hepatotoxicity from chemotherapy occurs frequently from an unpredictable or idiosyncratic reaction. Despite remarkable advances in our understanding of the mechanisms of action, pharmacodynamics, and interrelationships between the liver and chemotherapy, the underlying etiology of hepatic toxicity for various agents remains unexplained. Here, we present a concise review of the broad differential diagnosis for abnormal liver function tests (LFTs) in oncology patients.

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“…Free plasma concentrations of 17AAG in patients have been noted to be in the low 1 to 5 Amol/L range for up to 12 h after drug infusion, which is significantly higher than the required concentration of drug to inhibit HSP90 function (19). Many established therapeutic agents have also been shown to have varying toxicities in the liver, both killing hepatocytes and causing cholestasis, including 1-h-D-arabinofuranosylcytosine (20), arsenic trioxide (21), and platinum drugs (22).…”

Section: Introductionmentioning

confidence: 99%

17-Allylamino-17-demethoxygeldanamycin enhances the lethality of deoxycholic acid in primary rodent hepatocytes and established cell lines

Mitchell

Park

Guo

et al. 2007

Molecular Cancer Therapeutics

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Ansamycin antibiotics that target heat shock protein 90 function are being developed as anticancer agents but are also known to be dose limiting in patients due to hepatotoxicity. Herein, to better understand how the normal tissue toxicity of geldanamycins could be ameliorated to improve the therapeutic index of these agents, we examined the interactions of 17-allylamino-17-demethoxygeldanamycin (17AAG) and the secondary bile acid deoxycholic acid (DCA) in hepatocytes and fibroblasts. DCA and 17AAG interacted in a greater than additive fashion to cause hepatocyte cell death within 2 to 6 h of coadministration. As single agents DCA, but not 17AAG, enhanced the activity of extracellular signal-regulated kinase 1/2, AKT, c-Jun NH 2 -terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (MAPK). Combined exposure of cells to DCA and 17AAG further enhanced JNK1/2 and p38 MAPK activity. Inhibition of JNK1/2 or p38 MAPK, but not activator protein-1, suppressed the lethality of 17AAG and of 17AAG and DCA. Constitutive activation of AKT, but not MAPK/ extracellular signal-regulated kinase kinase 1/2, suppressed 17AAG-and DCA-induced cell killing and reduced activation of JNK1/2. DCA and 17AAG exposure promoted association of BAX with mitochondria, and functional inhibition of BAX or caspase-9, but not of BID and caspase-8, suppressed 17AAG and DCA lethality. DCA and 17AAG interacted in a greater than additive fashion to promote and prolong the generation of reactive oxygen species (ROS). ROS-quenching agents, inhibition of mitochondrial function, expression of dominant-negative thioredoxin reductase, or expression of dominant-negative apoptosis signaling kinase 1 suppressed JNK1/2 and p38 MAPK activation and reduced cell killing after 17AAG and DCA exposure. The potentiation of DCA-induced ROS production by 17AAG was abolished by Ca 2+ chelation and ROS generation, and cell killing following 17AAG and DCA treatment was abolished in cells lacking expression of PKR-like endoplasmic reticulum kinase. Thus, DCA and 17AAG interact to stimulate Ca 2+ -dependent and PKRlike endoplasmic reticulum kinase -dependent ROS production; high levels of ROS promote intense activation of the p38 MAPK and JNK1/2 pathways that signal to activate the intrinsic apoptosis pathway. [Mol Cancer Ther 2007;6(2):618 -32]

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Cytosine arabinoside induced liver damage: Histopathologic demonstration

Cited by 20 publications

References 11 publications

Some adverse effects of cytarabine in leukemic rats

Some adverse effects of cytarabine in leukemic rats

Hepatotoxicity Secondary to Chemotherapy

17-Allylamino-17-demethoxygeldanamycin enhances the lethality of deoxycholic acid in primary rodent hepatocytes and established cell lines

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