Association of Ipomoea carnea and BCG reduces birth defects caused by cyclophosphamide in rats

Latorre, Andréia Oliveira; Hueza, Isis Machado; Górniak, Silvana Lima

doi:10.1016/j.lfs.2006.09.033

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…CP is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well‐known and well‐studied teratogen, causing a variety of birth defects in the fetuses of pregnant women treated with the drug (Latorre et al, ). Previous studies in rodents have shown that exposure to CP during organogenesis caused fetal resorption, limb, digit, head, and growth abnormalities, and skeletal malformations (Mirkes, ; Park et al, ).…”

Section: Introductionmentioning

confidence: 99%

Exposure to Green Tea Extract Alters the Incidence of Specific Cyclophosphamide‐Induced Malformations

Logsdon

Herring

Lockard

et al. 2012

Birth Defects Research Pt B

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BACKGROUND Green tea extract (GTE) has been shown to have antioxidative properties due to its high content of polyphenols and catechin gallates. Previous studies indicated that catechin gallates scavenge free radicals and attenuate the effects of reactive oxidative species (ROS). Cyclophosphamide (CP) produces ROS, which can have adverse effects on development, causing limb, digit, and cranial abnormalities. The current study was performed to determine if exposure to GTE can decrease teratogenic effects induced by CP in CD-1 mice. METHODS From gestation days (GD) 6–13, mated CD-1 mice were dosed with 400 or 800 mg/kg/d GTE; 100, 200, 400, or 800 mg/kg/d GTE + CP; CP alone, or the vehicle. GTE was given by gavage. CP (20 mg/kg) was given by intraperitoneal injection on GD 10. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS The highest GTE dose did not effectively attenuate, and in some cases exacerbated the negative effect of CP. GTE alone was also associated with an increased incidence of microblepharia. Conversely, moderate GTE doses (200 &/or 400 mg/kg/d) attenuated the effect of CP on fetal weight and (GTE 200 mg/kg/d) decreased the incidences of certain defects resulting from CP exposure. CONCLUSIONS Exposure of a developing mammal to moderate doses of GTE can modulate the effects of exposure to CP during development, possibly by affecting biotransformation, while a higher GTE dose tended to exacerbate the developmental toxicity of CP. GTE alone appeared to cause an adverse effect on eyelid development.

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Section: Introductionmentioning

confidence: 99%

Exposure to Green Tea Extract Alters the Incidence of Specific Cyclophosphamide‐Induced Malformations

Logsdon

Herring

Lockard

et al. 2012

Birth Defects Research Pt B

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“…Cyclophosphamide (CPA), a clinical commonly used antitumor drug and also an immunosuppressant and immunomodulatory (Latorre et al, 2007), results in growth retardation and failure of neurulation. The process is accompanied by a time‐dependent increase in cellular damage and an appearance of apoptotic cells in the embryonic brain by an up‐expression of Bax and a down‐expression of the p65 subunit of NF‐κB (a redox‐sensitive transcription factor) and I κBα in the embryo (Mammon et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Developmental neurotoxicity role of cyclophosphamide on post‐neural tube closure of rodents in vitro and in vivo

Xiao

Zhao

et al. 2007

Intl J of Devlp Neuroscience

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To evaluate the possible developmental role of cyclophosphamide on post-neural tube closure of rodents, the 46 pregnant rats of 2.5-3 months old were randomly divided into five groups. On the 13th day of gestation, the rats in control and experimental groups were treated with physiological saline and cyclophosphamide (7.5, 10.5, 12.5 and 15.0 mg/kg bw), respectively. On the 14th day of gestation, three rats each selected randomly from control and experimental (12.5 mg/kg bw) group, respectively, were executed and the embryo brains were checked using both light microscope and transmission electron microscope. Neurocytotoxic effects of cyclophosphamide were determined using tetrazolium dye (MTT) assay, single cell gel electrophoresis, flow cytometry and scanning electron microscope. Compared with control group, the malformation incidence of the experimental groups (except the group 7.5 mg/kg bw) was significantly higher, especially in 12.5 mg/kg bw group (malformation incidence 98%, lethality 0). Neural tube serial section of fetus showed the apoptotic morphological features after 24 h cyclophosphamide administrated. Cyclophosphamide (8 microg/ml) decreased the growth and viability of neurons, damaged nuclear DNA and induced early apoptotic morphological changes. Our study shows that the teratogenesis of cyclophosphamide after neural tube closure are involved in cyclophosphamide-induced neuronal apoptosis and DNA damage.

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“…Failure of the neural tube to close during development results in exencephaly, anencephaly, and spina bifida. Nonspecific stimulation of maternal immune system in mice reduces a wide variety of fetal malformations induced by various physical and chemical agents, and also diseases such as diabetes mellitus (Nomura et al., ; Toder et al., ; Holladay et al., ; Prater et al., ; Punareewattana and Holladay ; Laudermilch et al., ; Khaksary et al., ; Latorre et al., ; Hrubec et al., ). Maternal immune stimulation with IFNγ reduces the incidence of valproic acid (VA) induced NTDs in late gestational fetuses (Hrubec et al., ).…”

Section: Introductionmentioning

confidence: 99%

Reduction in Valproic Acid–Induced Neural Tube Defects by Maternal Immune Stimulation: Role of Apoptosis

Mallela

Hrubec

2012

Birth Defects Research Pt B

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Teratogenic deregulation of apoptosis during development is a possible mechanism for birth defects. Administration of valproic acid (VA) during first trimester of pregnancy causes neural tube defects (NTDs). Nonspecific stimulation of the mother’s immune system has been shown to reduce various teratogen-induced fetal malformations including NTDs in rodents. This present study investigated the role of reduced apoptosis by maternal immune stimulation in prevention of VA-induced NTDs in CD-1 mice. Prevention of VA-induced NTDs by nonspecific maternal immune stimulation using IFNγ was employed to evaluate the role of reduced apoptosis by IFNγ in this protective mechanism. Apoptosis was quantified using flow cytometry. Terminal Transferase dUTP Nick End Labeling assay was used to localize the apoptosis. Increased apoptosis, suggesting involvement in VA teratogenicity, was observed along the neural tube in both normal and abnormal embryos from VA-exposed dams. Increased apoptosis in normal VA-exposed embryos suggests that VA may alter other cellular processes such as cell proliferation and differentiation in addition to apoptosis. Apoptotic levels in embryos with closed neural tubes from IFNγ + VA dams were similar to controls indicating resistance to VA-induced apoptosis and protection against teratogenicity of VA. In IFNγ + VA exposed embryos with open neural tubes, maternal immune stimulation failed to regulate apoptosis resulting in an NTD. Overall, these results suggest that VA alters several biological processes including apoptosis in the developing embryos to induce fetal malformations. Resistance to VA-induced apoptosis in embryos resulting from maternal immune stimulation may be involved in protective mechanism.

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Association of Ipomoea carnea and BCG reduces birth defects caused by cyclophosphamide in rats

Cited by 6 publications

References 25 publications

Exposure to Green Tea Extract Alters the Incidence of Specific Cyclophosphamide‐Induced Malformations

Exposure to Green Tea Extract Alters the Incidence of Specific Cyclophosphamide‐Induced Malformations

Developmental neurotoxicity role of cyclophosphamide on post‐neural tube closure of rodents in vitro and in vivo

Reduction in Valproic Acid–Induced Neural Tube Defects by Maternal Immune Stimulation: Role of Apoptosis

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