Maternal-fetal transport kinetics of manganese in perfused human placental lobule in vitro.

OBJECTIVE: There have been no detailed reports relating to maternal-fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro. METHODS: Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30 min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters. RESULTS: Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p < 0.05), while those of 10 and 50% efflux fractions were not significantly different between the study and reference substances. Transport fraction (TF) of manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Student's t-test, p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, elimination rate of manganese compared to reference marker were significantly different (ANOVA test, p < 0.05) between the study and reference substances. CONCLUSIONS: Our studies show for the first time maternal-fetal transport kinetics of manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental transport in "diabetic model" placental perfusions are in progress.

Influence of coconut oil administration on some hematologic and metabolic parameters in pregnant rats.

OBJECTIVE: Data on the effect of coconut oil intake on various hematologic and metabolic parameters in pregnant women or animals are scanty. Hence we attempted to assess the effect of oral administration of graded doses of this edible oil during pregnancy, on various hematologic and metabolic parameters in rats. METHODS: Groups of pregnant Sprague Dawley rats were given oral doses of 1 ml, 2 ml, and 4 ml coconut oil twice per day, respectively. Control group of rats were given tap water. Oral feeding of oil was done continuously for a period of 20 days and at the end of the study period the animals were lightly anaesthetized with ether and sacrificed to collect blood samples for analysis. Various hematologic parameters such as red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (Hg), platelets, lymphocytes, and mean corpuscular hemoglobin concentration (MCHC) were analyzed by a hematology blood analyzer, while metabolic parameters such as cholesterol, triglycerides, urea, uric acid, creatinine, and protein were analyzed by specific analytical kits. Activities of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant activity (TAO) were assessed by specific analytical kits. Statistical analysis of data was performed using a SPSS data analytical package. RESULTS: Oral administration of coconut oil for 20 continuous days of pregnancy did not significantly alter any of the hematologic parameters studied, compared to control group even when the oil was administered at a relatively massive dose of 4 ml/day. Administration of coconut oil appeared to decrease WBC, Hg, platelet, and lymphocyte blood concentrations in treated rats, but the difference, however, was not statistically significant (ANOVA test; p > 0.05). However, platelet concentration was significantly lower (p < 0.05) in rats receiving 1 ml/day of coconut oil compared to control group rats. Administration of coconut oil did not alter the concentrations of protein, cholesterol, urea, triglycerides, uric acid, and creatinine in treated groups of rats significantly (Student's t-test, p > 0.05) compared to those of control rats. SOD, GPX, and TAO levels in control and treated groups were not significantly different (ANOVA test, p > 0.05) than controls. CONCLUSIONS: We conclude that oral administration of coconut oil during pregnancy in rats, even in massive doses, does not cause any significant alterations in hematologic and metabolic parameters. More detailed studies, however, are warranted before extrapolating these results to human situations.

Transport kinetics of cisplatin in the perfused human placental lobule in vitro.

OBJECTIVE: Platinum-containing drugs are used extensively in the treatment of various malignancies in humans. Data are scarce on the maternal-fetal transport characteristics in humans of one such widely used drug, cisplatin, and this prompted us to study its transport characteristics in the human placenta in vitro. METHODS: Placentae from normal pregnancies were collected after delivery. Cisplatin, along with antipyrine as an internal reference marker, was injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution, was used as the perfusate. The concentration of cisplatin in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was quantified by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. RESULTS: The differential transport rate of cisplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.49 +/- 0.02, 1.23 +/- 0.03, 2.41 +/- 0.04, 3.67 +/- 0.03, and 4.48 +/- 0.07 minutes in 12 perfusions, while corresponding rates for antipyrine, for above mentioned efflux fractions averaged 0.51 +/- 0.01, 1.26 +/- 0.05, 2.52 +/- 0.01, 3.78 +/- 0.01, and 4.52 +/- 0.01 minutes, respectively. Cisplatin transport rates averaged 0.97, 0.97, 0.96, 0.97, and 0.99 times the antipyrine reference value. Analysis of variance (ANOVA) did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of cisplatin, expressed as a fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.6 +/- 2.01% of injected bolus dose, representing 13.10% of reference marker value. The Student's t-test showed cisplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, and elimination rate of study and reference substances also varied significantly (p < 0.05). CONCLUSIONS: We report for the first time that cisplatin transport is negligible in the human placenta at term. It is reasonable to assume that the risk for the neonate from cisplatin use in pregnancy is minimal when it is used in emergency clinical situations.

Maternal-fetal transport kinetics of carboplatin in the perfused human placental lobule: in vitro study.

OBJECTIVE: Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal-fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro. METHODS: Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. RESULTS: The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 +/- 0.10, 1.06 +/- 0.06, 1.00 +/- 0.02, 0.98 +/- 0.01, and 0.99 +/- 0.01, respectively, times the antipyrine reference value. Student's t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.60 +/- 2.01% of injected bolus dose, representing 13.1% of reference marker value. Student's t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences. CONCLUSIONS: We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.

Maternal-fetal transport kinetics of methotrexate in perfused human placenta: in vitro study.

OBJECTIVE: Folate antagonists are widely used in the treatment of diverse cancerous states. A paucity of data on transport characteristics of one such widely used drug, methotrexate, in the human placenta, prompted us to study its permeation characteristics in vitro. METHODS: Placentas from normal pregnancies were collected post-partum. Methotrexate, along with antipyrine as reference marker were injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules; perfusate samples were collected from both maternal and fetal circulations over a study period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. The concentration of methotrexate in various samples was determined by high performance liquid chromatography, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using standard parameters. RESULTS: Differential transport rate of methotrexate for 10, 25, 50, 75 and 90% efflux fractions in fetal venous effluent averaged 0.52, 1.30, 2.37, 3.57 and 4.43 minutes in 12 perfusions, representing 1.01 + 0.08, 1.03 + 0.06, 0.95 + 0.03, 0.93 + 0.03, 0.93 + 0.03 respectively times antipyrine reference value. Student's t-test showed varying differences between the control and study group data. Transport Fraction (TF) of methotrexate, expressed as fraction of the drug appearing in fetal vein, during study period of 5 minutes averaged 24.00 + 2.50% of bolus dose while antipyrine TF averaged 68.73 + 2.01% of injected bolus dose, representing 24.00 percent of reference marker value. Student's t-test showed methotrexate and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, absorption and elimination rates of study and reference substances showed varying differences. CONCLUSIONS: We report for the first time that the transport of methotrexate from maternal to fetal circulation is not negligible in human placenta at term. It is reasonable to assume that a direct risk for the fetus from methotrexate use in pregnancy cannot be excluded, and caution is warranted when it is used in emergency clinical situations.

Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation.

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 microg/L respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 microg/L respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu : Zn ratio in the maternal vein of the obese group (3.60 +/- 0.20) was significantly lower (Student's t-test; p < 0.05) than that of the controls (2.50 +/- 0.19); however, Cu : Fe ratio (1.04 +/- 0.08 vs 1.02 +/- 0.09) was not significantly different (Student's t-test; p > 0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.

Maternal-fetal transport and disposition of copper, iron, molybdenum, selenium and zinc in experimentally induced diabetic rats.

OBJECTIVE: To assess maternal-fetal status of essential trace elements such as copper, iron, molybdenum, selenium and zinc, in experimentally induced diabetic and control pregnant rats, and to correlate the findings with those observed in human diabetic pregnancies. Fetal-maternal ratios of the elements and Cu:Zn and Cu:Fe ratios were also computed in control and study groups. METHODS: Diabetes was experimentally induced in pregnant Sprague Dawley rats by injection of streptozotocin. A cocktail of essential trace elements along with antipyrine as internal reference marker were then injected intra-peritoneally to diabetic and matched control pregnant rats on the 20th day of pregnancy. Maternal and fetal blood and tissue samples were collected after sacrificing the animals at 30- and 60-minutes following cocktail injection. Concentrations of trace elements and antipyrine in various blood and tissue samples were then determined by atomic absorption spectrophotometry and colorimetry, respectively. RESULTS: Concentrations of Cu, Fe, Mo, Se, Zn, and antipyrine averaged 2907.0 +/- 212.0 microg/L, 3950.0 +/- 766.0 microg/L, 15.8 +/- 1.7 microg/L, 74.8 +/- 6.5 microg/L, 726.4 +/- 67.4 microg/L, and 170.5 +/- 8.2 mg/L, respectively, in maternal blood in control pregnant rats (n = 5) at day 20 in the 30-minute study phase, while in the diabetic group (n = 5) the values of the various trace element concentrations and antipyrine averaged 2875.0 +/- 225.0 microg/L, 5875.0 +/- 688.0 microg/L, 21.2 +/- 2.1 microg/L, 116.0 +/- 3.6 microg/L, 753.0 +/- 71.3 microg/L, and 171.7 +/- 4.2 mg/L, respectively. Unpaired student's t-test showed that Fe and Se levels were significantly higher (p < 0.05) in the diabetic pregnant rats compared to controls. Cu, Mo and Zn values, however, were not significantly different (p > 0.05) between the two groups. Cu:Zn and Cu:Fe ratios showed varying differences between maternal and fetal samples in the control and study groups. CONCLUSIONS: Considering the disparity of results in pregnant diabetic rats and pregnant diabetic women, we urge exercising caution when comparing data from animal studies to human situations.

Maternal-fetal status of copper, iron, molybdenum, selenium and zinc in insulin-dependent diabetic pregnancies.

OBJECTIVE: The objective was to assess the status of essential trace elements such as copper, iron, molybdenum, selenium and zinc in insulin-dependent diabetic pregnancies at term and to compare the data with a control group. Fetal-maternal ratios of the elements and copper:zinc ratio were also computed in the control and study populations. METHODOLOGY: Samples from maternal vein, umbilical artery and umbilical vein of diabetic and control women were collected at the time of spontaneous delivery or cesarean section and activities of trace elements evaluated by atomic absorption spectrophotometry. RESULTS: Cu, Fe, Mo, Se and Zn concentrations in maternal venous blood averaged 2,156, 2,020, 13, 102 and 656 microg/l in control women (n=17) while in the diabetic group (n=14), the corresponding values for the trace elements averaged 3,135, 3,675, 15, 85 and 628 microg/l respectively. Values for copper and molybdenum were significantly higher (p<0.05) in the study group compared to control while those of zinc, iron and selenium were not significantly different (p>0.05). Iron and molybdenum values were significantly higher (p<0.05) and that of zinc significantly lower (p<0.05) in umbilical arterial samples of diabetic group compared to controls. In the case of molybdenum, copper the values were significantly higher (p<0.05) in umbilical venous samples of diabetic group compared to that of control. Significant differences in Cu:Zn ratio of maternal venous and umbilical samples and fetal-maternal ratios of some elements were noted between control and study group as well. CONCLUSION: We speculate that altered status of some essential trace elements and altered antioxidant mineral ratio observed in insulin dependent diabetic patients could have deleterious influences on the health of the mother as well as the fetus and newborn.

Transport kinetics of alpha-aminoisobutyric acid and water in pre-eclamptic pregnancies: an in vitro study.

OBJECTIVE: To investigate the transport kinetics of a model amino acid, alpha-aminoisobutyric acid (AIB), in the maternal-fetal direction in placentae from pre-eclamptic pregnancies. METHODS: Transport kinetics of the amino acid was assessed in vitro using perfusion of human placental lobules. Control placental lobules were perfused for comparison. National Culture and Tissue Collection--135 medium diluted with Earle's buffered salt solution was used as the perfusate, and tritiated water served as the internal reference marker. AIB along with reference marker was injected as a single bolus into the maternal arterial perfusate, and serial perfusate samples were collected from maternal and fetal venous circuits for a study period of 5 min. RESULTS: The differential transport rate of the amino acid for various efflux fractions differed significantly between control and experimental groups when compared to that of the reference marker. The transport rate (corresponding to 50% of efflux into the fetal vein), transport fraction, absorption and elimination rates of the amino acid differed significantly compared to the reference marker values in study and control groups. CONCLUSION: The results indicate that amino acid transport function is compromised in placentae of pre-eclamptic pregnancies.