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Induction of size-dependent breakdown of blood-milk barrier in lactating mice by TiO2 nanoparticles.

Zhang C, Zhai S, Wu L, Bai Y, Jia J, Zhang Y, Zhang B, Yan B - PLoS ONE (2015)

Bottom Line: This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells.An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier.However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

ABSTRACT
This study aims to investigate the potential nanotoxic effects of TiO2 nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles are accumulated in mammary glands of lactating mice after i.v. administration. This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs (50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and are more potent in causing perturbations to blood-milk barrier. An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier. However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

No MeSH data available.


Related in: MedlinePlus

TNP exposure scheme and biodistribution of TNPs in lactating dams after intravenous injection.(A) TNP exposure scheme. Lactating dams received exposure of TNP-8 or TNP-50 at lactation day (LD) 2, 4, 6, and 8 at a dose of 2, 6 or 8 mg/kg body weight via intravenous administration. (B) Ti content in major organs of lactating dams at LD 10 after four doses of TNPs (8 mg/kg) at LD 2, 4, 6 and 8. Ti content in PBS group showed the basal Ti level in various organs. (C) Ti content in mammary glands at LD 10 after dams were exposed to four doses of TNPs at indicated doses at LD 2, 4, 6 and 8. The symbol * represents significant difference from the PBS group (P<0.05) and # represents significant difference from the TNP-8 group (P<0.05). In both B and C, data are mean±s.d. (n = 7 per group).
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pone.0122591.g002: TNP exposure scheme and biodistribution of TNPs in lactating dams after intravenous injection.(A) TNP exposure scheme. Lactating dams received exposure of TNP-8 or TNP-50 at lactation day (LD) 2, 4, 6, and 8 at a dose of 2, 6 or 8 mg/kg body weight via intravenous administration. (B) Ti content in major organs of lactating dams at LD 10 after four doses of TNPs (8 mg/kg) at LD 2, 4, 6 and 8. Ti content in PBS group showed the basal Ti level in various organs. (C) Ti content in mammary glands at LD 10 after dams were exposed to four doses of TNPs at indicated doses at LD 2, 4, 6 and 8. The symbol * represents significant difference from the PBS group (P<0.05) and # represents significant difference from the TNP-8 group (P<0.05). In both B and C, data are mean±s.d. (n = 7 per group).

Mentions: Although medicinal application of TNPs often involves a direct i.v. injection [6], environmental exposures through oral, dermal, or inhalation routes all lead to the absorption of nanoparticles into the circulation followed by the translocation of nanoparticles to various organs [17, 25, 29, 30]. During the lactation period, there is an increased blood flow to the mammary glands. This may facilitate the transfer of nanoparticles from blood to mammary glands [31]. Based on this, we chose i.v. administration for the toxic study of lactating mammary gland. To simulate these processes, we give mice four i.v. injections of TNPs at doses of 2, 6, and 8 mg/kg (Fig 2A).


Induction of size-dependent breakdown of blood-milk barrier in lactating mice by TiO2 nanoparticles.

Zhang C, Zhai S, Wu L, Bai Y, Jia J, Zhang Y, Zhang B, Yan B - PLoS ONE (2015)

TNP exposure scheme and biodistribution of TNPs in lactating dams after intravenous injection.(A) TNP exposure scheme. Lactating dams received exposure of TNP-8 or TNP-50 at lactation day (LD) 2, 4, 6, and 8 at a dose of 2, 6 or 8 mg/kg body weight via intravenous administration. (B) Ti content in major organs of lactating dams at LD 10 after four doses of TNPs (8 mg/kg) at LD 2, 4, 6 and 8. Ti content in PBS group showed the basal Ti level in various organs. (C) Ti content in mammary glands at LD 10 after dams were exposed to four doses of TNPs at indicated doses at LD 2, 4, 6 and 8. The symbol * represents significant difference from the PBS group (P<0.05) and # represents significant difference from the TNP-8 group (P<0.05). In both B and C, data are mean±s.d. (n = 7 per group).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388820&req=5

pone.0122591.g002: TNP exposure scheme and biodistribution of TNPs in lactating dams after intravenous injection.(A) TNP exposure scheme. Lactating dams received exposure of TNP-8 or TNP-50 at lactation day (LD) 2, 4, 6, and 8 at a dose of 2, 6 or 8 mg/kg body weight via intravenous administration. (B) Ti content in major organs of lactating dams at LD 10 after four doses of TNPs (8 mg/kg) at LD 2, 4, 6 and 8. Ti content in PBS group showed the basal Ti level in various organs. (C) Ti content in mammary glands at LD 10 after dams were exposed to four doses of TNPs at indicated doses at LD 2, 4, 6 and 8. The symbol * represents significant difference from the PBS group (P<0.05) and # represents significant difference from the TNP-8 group (P<0.05). In both B and C, data are mean±s.d. (n = 7 per group).
Mentions: Although medicinal application of TNPs often involves a direct i.v. injection [6], environmental exposures through oral, dermal, or inhalation routes all lead to the absorption of nanoparticles into the circulation followed by the translocation of nanoparticles to various organs [17, 25, 29, 30]. During the lactation period, there is an increased blood flow to the mammary glands. This may facilitate the transfer of nanoparticles from blood to mammary glands [31]. Based on this, we chose i.v. administration for the toxic study of lactating mammary gland. To simulate these processes, we give mice four i.v. injections of TNPs at doses of 2, 6, and 8 mg/kg (Fig 2A).

Bottom Line: This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells.An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier.However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

ABSTRACT
This study aims to investigate the potential nanotoxic effects of TiO2 nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles are accumulated in mammary glands of lactating mice after i.v. administration. This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs (50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and are more potent in causing perturbations to blood-milk barrier. An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier. However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

No MeSH data available.


Related in: MedlinePlus