Jinsoo Lee

Effects of silver nanoparticles on pregnant dams and embryo-fetal development in rats

Abstract Although the potential risk of silver nanoparticles (AgNPs) to humans has recently increased due to widespread application, the potential effects of AgNPs on embryo-fetal development have not yet been determined. This study investigated the potential effects of AgNPs on pregnant dams and embryo-fetal development after maternal exposure on gestational days (GD) 6–19 in rats. AgNPs were administered to pregnant rats by gavage at concentrations of 0, 100, 300, and 1000u2009mg/kg/day. All dams were subjected to Cesarean section on GD 20 and the fetuses were examined for signs of embryotoxic and teratogenic effects. Examinations of hepatic oxidant/antioxidant balance and serum biochemistry were also added to the routine developmental toxicity study. Treatment with AgNPs caused a decrease in catalase and glutathione reductase activities at ≥100u2009mg/kg/day and a reduction in glutathione content at 1000u2009mg/kg/day in maternal liver tissues. However, no treatment-related deaths or clinical signs were observed in any of the animals treated with AgNPs. No treatment-related differences in maternal body weight, food consumption, gross findings, serum biochemistry, organ weight, gestation index, fetal deaths, fetal and placental weights, sex ratio, or morphological alterations were observed between the groups. The results show that repeated oral doses of AgNPs during pregnancy caused oxidative stress in hepatic tissues at ≥100u2009mg/kg/day, but did not cause developmental toxicity at doses of up to 1000u2009mg/kg/day. The no-observed-adverse-effect level of AgNPs is considered to be <100u2009mg/kg/day for dams and 1000u2009mg/kg/day for embryo-fetal development.

2,5-Pyridinedicarboxylic acid derivatives as non-nucleosidic reverse transcriptase inhibitors of hepatitis B virus

2,5-Pyridinedicarboxylic acid derivatives were found to be the potent non-nucleoside inhibitors of hepatitis B virus (HBV) with IC(50) <or=0.01 microg/mL in a reverse transcriptase inhibitory effect. And they showed the low toxicity compared with the nucleoside analogues.

Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats

Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20xa0mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20xa0mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20xa0mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5xa0mg/kg in dams and no observed adverse effect level was suggested to be 10xa0mg/kg in fetal developmental toxicity.

Developmental and reproductive toxicity assessment in rats with KGC-HJ3, Korean red ginseng with Angelica gigas and Deer antlers

Background Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. Methods This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague–Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague–Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. Results and conclusion No test item–related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.

Toxicity and tissue distribution of cerium oxide nanoparticles in rats by two different routes: single intravenous injection and single oral administration

Toxicity and target organ distribution of cerium oxide nanoparticles (CeNPs) were investigated via single intravenous injection and single oral administration, respectively. Rats were sacrificed at 24xa0h after treatment with doses of 30 and 300xa0mg/kg, and cerium concentrations were measured in liver, kidney, spleen, lung, blood, urine and feces. Results revealed cerium levels in blood and tissues were considerably low in oral treated groups and most cerium was detected in feces, meaning CeNPs would not be absorbed in the gastro-intestinal system. Conversely, high concentrations of cerium were detected in all tissues of rats after intravenous injection. Liver and spleen were main target organs. Cerium levels in liver were 594.9u2009±u200995.3xa0μg/g tissue in 30xa0mg/kg treat group and 3741.7u2009±u2009932.7xa0μg/g tissue in 300xa0mg/kg treat group. Cerium levels in spleen reached almost levels of liver. Cerium was also detected, that is relatively low compared to oral administration, in feces of rats treated via intravenous injection, that supports biliary excretion of CeNPs. Urine excretion of CeNPs was not detected in oral treatment and intravenous injection. In accordance with level of cerium distribution, toxicities based on hematology, serum biochemistry and histopathology were observed in rats treated by intravenous injection while no significance was revealed in orally treated groups.

Developmental toxicity assessment of the new turf herbicide, methiozolin ([5-(2,6-difluorobenzyl)oxymethyl-5-methyl-3,3(3-methylthiophen-2-yl)-1,2-isoxazoline]), in rabbits.

Methiozolin is a new herbicide to control annual bluegrass (Poa annua L.) and large crabgrass (Digitaria sanguinalis (L.) Scop.) in various turfgrasses. The potential of methiozolin to induce maternal and developmental toxicity was investigated in the pregnant New Zealand White Rabbits. Methiozolin was, at dose levels of 0, 125, 250 and 500 mg/kg/day, administered by oral gavage to artificially inseminated rabbits (25 females per group) from days 6 to 28 of gestation. All does were subjected to Cesarean section on day 29 of gestation. At 500 mg/kg/day, treatment-related toxicities including abortion (10/22), decreased mean body weight, weight gain, net body weight change, reduced food consumption and decreased fetal weight were observed. At 125 and 250 mg/kg/day, no signs of maternal and developmental toxicity were observed. There were no treatment-related external, visceral and skeletal abnormalities of fetuses at all doses tested. In the current experimental conditions, the no observed adverse effect levels (NOAELs) of methiozolin are considered to be 250 mg/kg/day for does and prenatal development.