Although there are some indications that flavonoids might be involved in leukemogenesis Spector et al. Our previous data Barjesteh van Waalwijk van Doorn-Khosrovani et al.
Because the concentrations used in this in vitro study can also be obtained in vivo and knowing that flavonoids can penetrate the placenta and accumulate in the fetus Adlercreutz et al. Fetal cells are rapidly proliferating cells and thus have high topoII activity Zandvliet et al. As flavonoids execute their clastogenicity through inhibiting the religation of DSBs, one might expect that any defect in DSB repair may predispose cells to clastogenic effects of these compounds.
Ye et al. Hence, ATM phosphorylates its downstream targets e. Patients with mutations in the ATM gene are prone to developing chromosomal abnormalities Khanna, ; Oguchi et al. Heterozygous germ line mutations in the ATM gene are frequent and occur in 0.
These mutations are associated with an increased risk for developing different types of cancer, including leukemia Gumy-Pause et al. After exposure, cells were washed twice and left to recover for another day before DNA isolation.
Cell counts and viability were determined by a hemocytometer and trypan blue exclusion. After delivery, all mothers and pups received the normal chow. At day 5 after birth, pups were weighted and genotype and gender were determined. At 12 weeks of age, offspring were sacrificed by cardiac puncture and checked for tumor development and blood was collected in EDTA tubes Terumo, Leuven, Belgium to determine the blood composition. Bone marrow was isolated by removing the femurs and flushing the marrow with PBS.
Offspring that died before sacrificing day were also checked for tumor development. The presence of a vaginal plug the next morning was defined as 0. On day Subsequently, the smears were stained with Giemsa solution Merck, Darmstadt, Germany for 20 min and washed again in tap water. All preparations were judged by an experienced animal pathologist. Genomic DNA was isolated from bone marrow cells in vitro culture or in vivo from week-old mice and from the fetal liver of E The purified PCR products were subsequently sequenced using big dye v3.
The nonparametric Mann-Whitney test was used to compare the distribution of gender, genotype, pup survival, litter sizes, average weight of pups at postnatal day 5, and tumor development between litters of the different diet groups. Cell viability was evaluated by trypan blue exclusion. We observed no significant decrease in cell viability because of exposure to either flavonoids or etoposide or because of genotype of bone marrow cells in comparison with DMSO-treated cells Fig.
Cells were allowed to repair the DSBs for 24 h in a drug-free medium. In contrast, exposure of bone marrow cells to quercetin, genistein, or etoposide generated multiple bands of different sizes. The variety in the size of PCR products was determined by both the location of the break point junction in Mll and the position of the PciI site in the fusion partner.
Smaller sized bands were more likely to be detected by inverse PCR than the wt Mll because wt Mll is more difficult to amplify because of its length. Sequencing of the break point junction of several distinct Mll translocations induced by flavonoids or etoposide confirmed that the bands of aberrant size were indeed translocations Table 4.
This indicates that the Atm mutation predisposes cells to the clastogenic effects of flavonoids. The samples were visualized by gel electrophoresis. Each band with a size different from the wt 5. There were no differences in gender ratio, average weight of the offspring measured at day 5 after birth, or average litter size between control, genistein-, or quercetin-exposed groups Table 2. Interestingly, the incidence of different genotypes was to some extent affected by prenatal diet.
The genistein and quercetin diet groups, however, had different prevalences of the genotypes. In the genistein group, the percentage of heterozygote animals seemed to be low; however, the distribution of distinct genotypes was not significantly different from the control group.
General characteristics of the litters prenatally exposed to genistein-, quercetin-supplemented, or normal diet. Average number of deceased pups after birth and before sacrifice day week A total number of 45 control, 45 genistein-, and 40 quercetin-exposed mice reached the age of 12 weeks. The percentage of animals that died before this time point was not significantly different for all three diet groups Table 2.
We were unable to determine the cause of death, but at autopsy, no tumors were noted. The mice that reached 12 weeks of age were sacrificed, and their internal organs were examined for visual signs of abnormalities and presence of gross tumors Table 2. In a previous study Spring et al. In our study, several mice had already developed malignancies at 12 weeks of age.
Blood count and blood smear examination showed concomitant ALL in two mice that were exposed to genistein. In general, leukemia and thymoma were only detected in mice that were homozygous for the Atm mutation.
The only heterozygous mouse that was diagnosed with malignancy fallopian tube tumor belonged to the genistein group. Altogether, mut mice prenatally exposed to genistein showed a slightly higher risk for developing tumors and leukemia compared with wt control mice. This research was carried out within the framework of a research project no. National Center for Biotechnology Information , U.
Evid Based Complement Alternat Med. Published online Dec 2. Author information Article notes Copyright and License information Disclaimer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract Since improving maternal and child health is a public health priority worldwide, the main aim of treatment of hypertension in pregnant women is to prevent complications during pregnancy, labor, and postpartum. Pathology of Pregnancy-Induced Hypertension The increasing number of patients suffering from cardiovascular diseases, including hypertension being often developed during pregnancy, indicates the need for innovative strategies for more effective prevention and treatment [ 1 ].
Searching for New Pharmacological Strategies for Pregnancy-Induced Hypertension The main aim of treatment of hypertension in pregnant women is to prevent complications throughout pregnancy, during childbirth and postpartum. The Issue of the Use of Herbal Extracts during Pregnancy Application of herbal products is one of the methods in complementary and alternative medicine [ 70 ]. Flavonoids as Active Natural Chemical Compounds Plant flavonoids and their conjugates belong to a large family of natural phenylpropanoid-derived polyphenolic compounds that are commonly found in many species of medicinal plants from different families, i.
Open in a separate window. Figure 1. Quercetin Intake during Pregnancy It is known that several flavonoids can cross the placenta and may be accumulated in fetal tissue [ 96 , 97 ]. In Vitro Studies of Mechanism of Action 7. Animal Cells There are many studies that focus on anti-inflammatory activity of quercetin and its impact on growth factors in various in vitro models [ — ], which can be taken into account in therapy of pregnancy-induced hypertension Figure 2.
Figure 2. Human Cells Quercetin showed protective effects against inflammation in human umbilical vein endothelial cells via the downregulation of vascular cell adhesion molecule 1 VCAM-1 [ ]. In Vivo Studies Several studies have stressed that quercetin showed free radical scavenger properties [ — ], which makes this flavonoid a well-established antioxidant that may be potentially used in prevention and treatment of cardiovascular disorders, even more as quercetin was reported to reduce oxidative damage to the brain, heart, and other tissues during ischemic reperfusion injury and exposure to compounds that induce oxidative stress [ , ].
Antihypertensive Activity of Quercetin In Vivo Quercetin has been shown to induce a progressive, dose-dependent, and sustained reduction in blood pressure when given chronically in several rat models of experimental hypertension, including spontaneously hypertensive rats SHR , rats with hypertension induced by inhibition of NO synthase with N-nitro-L-arginine methyl ester L-NAME , deoxycorticosterone acetate DOCA -salt hypertensive rats, rat model of renovascular hypertension with reduced blood flow to one kidney, and rat genetic model of metabolic syndrome [ 23 — 35 , , ].
Table 1 Recent experimental pharmacological in vivo studies on quercetin. Flavonoid Animal model Dose Main results Ref. Clinical Trials and Meta-Analysis Several human clinical trials have been conducted so far to estimate the efficacy of quercetin intake in the reduction of risk for hypertension and in hypertension treatment [ 36 — 42 ]. Table 2 Recent randomized controlled trials of quercetin-based formulations and hypertension. Other Natural Compounds Tested Apigenin has recently gained attention as an alternative flavonoid compound for prevention and treatment of PIH.
Potential Problems with the Use of Quercetin Using quercetin as pharmacologic therapy in the form of dietary supplementation may encounter few problems.
Safety Data from Clinical Trials Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature [ ].
Conclusion In summary, review of results of pharmacological studies shows that quercetin possesses antihypertensive activity via various mechanisms of action. Acknowledgments This research was carried out within the framework of a research project no.
Conflicts of Interest The authors declare that they have no conflicts of interest. References 1. Townsend R. Current best practice in the management of hypertensive disorders in pregnancy. Integrated Blood Pressure Control. Mammaro A. Hypertensive Disorders of Pregnancy. Journal of Prenatal Medicine. Luanni V. Fauci A. Disorders of intermediary metabolism. In: Fauci A. Masoura S. Biomarkers in pre-eclampsia: A novel approach to early detection of the disease. Myatt L. Preeclampsia: Syndrome or Disease?
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Dietary Sources Fruits and vegetables are the primary dietary sources of quercetin, particularly citrus fruits, apples, onions, parsley, sage, tea, and red wine. Available Forms Quercetin supplements are available as pills or capsules.
How to Take It Pediatric There is not enough evidence to recommend quercetin for children. Adult Recommended adult dosages of quercetin vary depending on the condition being treated. Probiotics are living microorganisms that are thought to benefit digestive health. Many studies have shown that probiotics are safe to take during pregnancy, and no harmful side effects have been identified, aside from an extremely low risk of probiotic-induced infection.
Additionally, several studies have shown that supplementing with probiotics may reduce the risk of gestational diabetes, postpartum depression, and infant eczema and dermatitis. Research on probiotic use in pregnancy is ongoing, and more about the role of probiotics in maternal and fetal health is sure to be discovered. The current recommended daily allowance of choline during pregnancy mg per day has been thought to be inadequate and that an intake closer to mg per day is optimal instead.
A separate choline supplement may be recommended by your doctor. While supplementing with some micronutrients and herbs is safe for pregnant women, many of them should be avoided, or avoided in high amounts.
Always check with your doctor before adding any additional supplements outside of any prenatal vitamins you may be taking. Although this vitamin is extremely important for fetal vision development and immune function, too much vitamin A can be harmful. Given that vitamin A is fat soluble , your body stores excess amounts in the liver.
This accumulation can have toxic effects on the body and lead to liver damage. It can even cause birth defects. For example, excessive amounts of vitamin A during pregnancy has been shown to cause congenital birth abnormalities. Between prenatal vitamins and foods, you should be able to get enough vitamin A, and additional supplementation outside of your prenatal vitamins is not advised.
This fat-soluble vitamin plays many important roles in the body and is involved in gene expression and immune function. Extra supplementation with vitamin E has not been shown to improve outcomes for either mothers or babies and may instead increase the risk of abdominal pain and premature rupture of the amniotic sack. A member of the buttercup family, black cohosh is a plant used for a variety of purposes, including controlling hot flashes and menstrual cramps.
Goldenseal contains a substance called berberine , which has been shown to worsen jaundice in infants. It can lead to a condition called kernicterus, a rare type of brain damage that can be fatal.
Dong quai is a root that has been used for over 1, years and is popular in traditional Chinese medicine. You should avoid dong quai, as it may stimulate uterine contractions, raising the risk of miscarriage. This herb should never be used during pregnancy, as it has been associated with dangerous side effects like high blood pressure, heart attacks, and seizures.
Pregnancy is a time of growth and development, making health and nutrition a top priority. Taking the best care of that little one is the goal.
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