Review of the potential effects of three commonly used antineoplastic and immunosuppressive drugs (cyclophosphamide, azathioprine, doxorubicin on the embryo and placenta)

Matalon, Shay; Ornoy, Asher; Lishner, Michael

doi:10.1016/j.reprotox.2003.10.014

Cited by 95 publications

(61 citation statements)

References 117 publications

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“…Thus, when transition metal ions were chelated by EDTA, antitumor activity might be influenced by a reduction in ROS. 23,38 From the spleen index and thymus gland index results, the superiority of the NH 4 EDTA-L preparation was quite apparent, because of lesser tissue accumulation in these organs and the chelating effect of EDTA. DOX cytotoxicity generally manifests as high levels of ROS and low levels of antioxidants and protective enzymes.…”

Section: Discussionmentioning

confidence: 99%

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

Song¹,

Huang²,

Song³

et al. 2014

IJN

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The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH 4 EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug-related cytotoxicity. The particle size of the optimum NH 4 EDTA gradient liposomes was 79.4±1.87 nm, and the entrapment efficiency was 95.54%±0.59%. In vitro studies revealed that liposomes prepared using an NH 4 EDTA gradient possessed long-term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg) prepared by (NH 4 ) 2 SO 4 gradient, NH 4 EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH 4 EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity.

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Section: Discussionmentioning

confidence: 99%

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

Song¹,

Huang²,

Song³

et al. 2014

IJN

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“…Recently, there has been a growing interest in studying the effect of different drugs, including chemotherapeutic agents, on the placenta. [62][63][64] For example, the adverse effects of 6-mercaptopurine on the placenta have been documented with inhibition of both migration and proliferation of trophoblast cells in first-trimester human placental explants. 62 Furthermore, placental perfusion studies can provide valuable information regarding both transfer and biotransformation of different drugs in the human placenta.…”

Section: Future Perspectivesmentioning

confidence: 99%

The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy

Pereg

Koren²,

Lishner³

2007

Haematologica

117

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Lymphoma is the fourth most frequent malignancy diagnosed during pregnancy, occurring in approximately 1:6000 of deliveries. Its occurrence may increase due to the current trend to postpone pregnancy until later in life and the suggested high incidence of AIDS-related non-Hodgkin's lymphoma in developing countries. The relatively rare occurrence of pregnancy-associated lymphoma precludes the conduction of large, prospective studies to examine diagnostic, management and outcome issues. Chemotherapy and radiotherapy during the first trimester are associated with increased risk of congenital malformations and this risk diminishes as pregnancy advances. In the vast majority of cases, when lymphoma is diagnosed during the first trimester, treatment with a standard chemotherapy regimen, following pregnancy termination should be recommended. In the rare patients at low risk, such as those with stage 1 Hodgkin's lymphoma or indolent non-Hodgkin's lymphoma, therapy can be delayed until the end of the first trimester and of embryogenesis while keeping the patients under close observation. When lymphoma is diagnosed during the second and third trimesters, evidence exists suggesting that full-dose chemotherapy can be administered safely without apparent increased risk of severe adverse fetal outcome.

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“…6-MP induces embryo-toxic effects, including a reduction in the number of implantation sites and is also known as a teratogen, inducing limb defects, micrognathia, ventral hernia, skeletal, urogenital, central nervous system and ocular anomalies, cleft palate, diaphragmatic hernia, etc. in rats, mice and rabbits [1,2,13,18,19]. On the other hand, Bargnoier et al suggested that placental tissues may be more sensitive to 6-MP than the fetus, and it is known that the placentas from 6-MP-treated rats show a disproportionate reduction in thickness of the labyrinth zone with fibrinous degeneration of trophoblasts [3,24].…”

mentioning

confidence: 99%

Effect of 6-Mercaptopurine on Rat Placenta

et al. 2008

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ABSTRACT. In order to investigate the toxic effects of 6-mercaptopurine (6-MP) on placental development, we examined sequential morphology in the placentas from rats exposed to 6-MP. 6-MP was intraperitoneally administered at 60 mg/kg during gestation days (GDs) 11 to 12, and the placentas were sampled on GD 13, 15 or 21. In the 6-MP-treated group, maternal body weight suppression, increased death embryo/fetus ratio and some malformations were observed. The placenta weights were decreased on GDs 15 and 21. Macroscopically, placentas on GD 21 were small, brittle and thin with a white peripheral rim. Histopathologically, in the labyrinth zone, 6-MP treatment mainly evoked decreased mitosis on GDs 13 and 15, increased apoptotic cell on GDs 13, 15 and 21 and thinning on GDs 15 and 21. In the basal zone, 6-MP evoked decreased mitosis on GDs 13, and PAS-positive material in the spongiotrophoblasts was still detected on GD 15. Thickening of the basal zone was observed with cytolysis of glycogen cells, apoptosis and an increased number of composed cells on GD 21. In conclusion, 6-MP administration in pregnant rats induced growth arrest of the labyrinth zone and developmental delay in the basal zone, leading to small placentas. The fetotoxicity of 6-MP may be responsible for its direct anti-proliferative effects and resulting placental dysfunction.

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Review of the potential effects of three commonly used antineoplastic and immunosuppressive drugs (cyclophosphamide, azathioprine, doxorubicin on the embryo and placenta)

Cited by 95 publications

References 117 publications

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy

Effect of 6-Mercaptopurine on Rat Placenta

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