Cyclophosphamide Toxicity

Fraiser, Lucy; Kanekal, Sarathchandra; Kehrer, James P.

doi:10.2165/00003495-199142050-00005

Cited by 377 publications

(123 citation statements)

References 55 publications

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“…The mixture was then cooled immediately and the absorbance was measured at 532 nm by spectrophotometer (UV-1650 PC, Shimadzu, Japan). The concentration of MDA was calculated based on the absorbance coefficient of the TBA-MDA complex (ε = 1.56×10 5 cm…”

Section: Malondialdehyde Levels Assaymentioning

confidence: 99%

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Ameliorative effects of hydroalcoholic extract of Lavandula officinalis L. on cyclophosphamide-induced nephrotoxicity in mice

Sadeghi¹,

Kalantar²,

Molavinia³

et al. 2017

J Nephropathol

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Background: Cyclophosphamide (CP) is amongst the most effective alkylating anticancer drugs which regardless of its harmful side effects including nephrotoxicity, hematotoxicity, mutagenicity and also immunotoxicity, commonly raised for the treatment of a number of cancers and autoimmune ailments. Objectives: This study was undertaken to investigate the ameliorative effect of Lavandula officinalis L extract (LOE) in nephrotoxicity induced by CP in mice. Materials and Methods:In this experimental study, 35 male Swiss albino mice (20-25 g) were randomly divided into 5 groups, each group consist of 7 mice. Mice were pretreated with LOE orally in doses of 100, 200 and 400 mg/kg for 5 consecutive days and CP (200 mg/kg, ip) was administrated on the fifth day 1 hour after the last dose of extract. Then on the sixth day, animals were sacrificed. Blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Malondialdehyde (MDA), glutathione (GSH) levels and catalase (CAT) and superoxide dismutase (SOD) activity were assayed in kidney tissue. The kidney was maintained in formalin for histological examination. Results: Results showed a significant increase in the levels of MDA, Cr and BUN, and decrease of GSH, CAT and SOD by CP administration. Pre-treatment with LOE showed reduction in the levels of MDA, Cr and BUN and increase of GSH, CAT and SOD in all doses but the most significant alteration was observed at doses of 200 and 400 mg/ kg (P < 0.05). Additionally the nephroprotective effect of the LOE was established by the histological examination of the kidneys. Conclusions: Our results indicated that LOE has produced amelioration in biochemical indices and oxidative stress parameters against CP-induced nephrotoxicity.

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Section: Malondialdehyde Levels Assaymentioning

confidence: 99%

“…The two active metabolite of CP is phosphoramide mustard (PAM) and acrolein (ACR). CP antineoplastic effects are related to PAM, although ACR is responsible for its toxic unwanted side effects (5). The ACR leads the cellular injury after binding with the glutathione (GSH) and also decreased their amount in the cell.…”

Section: Introductionmentioning

confidence: 99%

Ameliorative effects of hydroalcoholic extract of Lavandula officinalis L. on cyclophosphamide-induced nephrotoxicity in mice

Sadeghi¹,

Kalantar²,

Molavinia³

et al. 2017

J Nephropathol

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“…The teratogenic potential of CP is mainly associated with DNA damage induced by its metabolites such as phosphoramide mustard and acrolein [86,87]. CP is also capable of inducing ROS and oxidative stress [88], suggesting that the teratogenic mechanism of CP may be similar to that of diabetes.…”

Section: Possible Mechanisms Underlying the Tnfα-regulated Response Tmentioning

confidence: 99%

TNFalpha in the Pathogenesis of Diabetes-Induced Embryopathies: Functions and Targets

Torchinsky¹,

Toder²

2007

Rev Diabet Stud

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■ AbstractHyperglycemia-induced increase in the production of reactive oxygen species (ROS) is proposed to be an initial step in the pathogenesis of diabetes-induced spontaneous abortions and structural inborn anomalies. However, the subsequent steps in this process are incompletely understood. One of the key molecules involved is tumor necrosis factor-alpha (TNFα): its expression is regulated by ROS and it regulates ROS production in turn. This cytokine has been the focus of many studies addressing the mechanisms of different forms of diabetes-induced embryopathies, such as early pregnancy loss, inborn anomalies, fetal growth retardation as well as some pathologies appearing during adult life. In this review, we analyze the results of these studies and discuss how TNFα may regulate the response of pre-and postimplantation stage embryos to diabetes-induced detrimental stimuli. The data presented in this review suggest that TNFα may play a dual role in the pathogenesis of diabetes-induced embryopathies. It may act both as a mediator of diabetesinduced embryotoxic stimuli leading to the death of periimplantation stage embryos and, possibly, as a suppressor of diabetes-induced apoptosis in post-implantation stage embryos. It also appears that TNFα fulfills these functions via interaction with leukemia inhibitory factor (LIF) and the transcription factor NF-κB. These molecules are presently considered as attractive targets for the treatment of diabetesinduced complications. Therefore, further studies addressing their role in the mechanisms underlying diabetes-induced embryopathies are needed to evaluate the safety of such therapies for diabetic women of childbearing age.

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“…In addition to the HC, CP may also have toxic effects on the testis and there are several studies reporting this drug to have a negative effect on human fertility [8,9,10]. Because CP has cytotoxic effects on rapidly dividing cells, testes may be more sensitive to the toxic effects of this drugs than many other organs.…”

Section: Introductionmentioning

confidence: 99%

Effects of Tadalafil on Hemorrhagic Cystitis and Testicular Dysfunction Induced by Cyclophosphamide in Rats

Yiğitaslan¹,

Özatik²,

Özatik

et al. 2013

Urol Int

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Introduction: The protective and/or therapeutic potential of tadalafil (TDL) on cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) and testicular dysfunction in rats was evaluated. Materials and Methods: The animals except from the control group were divided into four groups and treated with saline, or 1, 5 or 10 mg/kg TDL orally (CP, TDL1, TDL5 and TDL10 groups, respectively) before and after CP injection. Body and organ weights, sperm count, cGMP, nitric oxide (NO), IL-6 and IL-10 levels in serum and bladder tissue, and serum testosterone (T), LH and FSH levels were determined. The histological analysis of bladder and testis was performed and the number of apoptotic cells was determined. Results and Conclusion: The CP group had decreased cGMP and NO levels in the bladder, serum T level (p < 0.05) and sperm count (p < 0.001) and higher IL-6 levels in serum and bladder (p < 0.01). Treatment with TDL resulted in increased cGMP (p < 0.001), NO (p < 0.05) and serum T (p < 0.05) levels. Histological analysis of the CP group showed severe HC in bladder and testicular damage. TDL-treated animals showed a dose-dependent improvement in all of these histological impairments. In conclusion, a selective inhibitor of phosphodiesterase-5 enzyme, TDL, showed a protective and/or therapeutic effect on CP-induced HC and testicular dysfunction in rats.

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Cyclophosphamide Toxicity

Cited by 377 publications

References 55 publications

Ameliorative effects of hydroalcoholic extract of Lavandula officinalis L. on cyclophosphamide-induced nephrotoxicity in mice

Ameliorative effects of hydroalcoholic extract of Lavandula officinalis L. on cyclophosphamide-induced nephrotoxicity in mice

TNFalpha in the Pathogenesis of Diabetes-Induced Embryopathies: Functions and Targets

Effects of Tadalafil on Hemorrhagic Cystitis and Testicular Dysfunction Induced by Cyclophosphamide in Rats

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