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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

Determination of levels of MDA (A), GSH (B), Linear correlation between dose and MDA in mammary gland (C) and comparison of TNP generated oxidative stress in mammary glands and liver (D) at LD 10 after four doses of TNP exposures (8 mg/kg) at LDs 2, 4, 6 and 8.Seven mice in each group were examined. Data are mean±s.d. (n = 7 per group). Values in "" are hypothetical values when the internal dose in mammary gland were 1000 μg Ti/g tissue. The symbol * represents significant difference from the PBS group (P<0.05). ΔMDA = (Liver MDA in TNP groups)–(Liver MDA in PBS groups). . ΔGSH and GSH per 1000 μg were obtained similarly.
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pone.0122591.g003: Determination of levels of MDA (A), GSH (B), Linear correlation between dose and MDA in mammary gland (C) and comparison of TNP generated oxidative stress in mammary glands and liver (D) at LD 10 after four doses of TNP exposures (8 mg/kg) at LDs 2, 4, 6 and 8.Seven mice in each group were examined. Data are mean±s.d. (n = 7 per group). Values in "" are hypothetical values when the internal dose in mammary gland were 1000 μg Ti/g tissue. The symbol * represents significant difference from the PBS group (P<0.05). ΔMDA = (Liver MDA in TNP groups)–(Liver MDA in PBS groups). . ΔGSH and GSH per 1000 μg were obtained similarly.

Mentions: The generation of oxidative stress by nanomaterials is suggested to be one of the main reasons for nanoparticle-induced tissue damages in testis [19], brain [27, 37], liver [38, 39], placenta and fetuses [18, 40]. Moreover, neutrophil-induced oxidative stress was found to damage mammary gland tissues in animals with mastitis (inflammation of the breast) [41, 42]. The accumulation of TNPs in lactating mammary glands suggested that TNPs might generate local oxidative stress. To evaluate the oxidative stress level in mammary glands, we analyzed the concentrations of two oxidative stress markers, malondialdehyde (MDA) and glutathione (GSH), in mammary glands. The exposure of the dams to TNP-8 and TNP-50 at 8 mg/kg increased the MDA level and decreased the GSH level in mammary glands (Fig 3A and 3B). The mammary glands exhibited a considerably lower antioxidative capability than the liver, as indicated by a comparison of the net increases in MDA and decreases in GSH in mammary glands and liver when the internal doses of TNPs were normalized to the same value (Fig 3C). As shown in Fig 3C, the TNP-induced oxidative stress in mammary glands would be 15–130 times higher than that in the liver if the internal dose were normalized to the same level. This indicated that mammary glands were more vulnerable to nanoparticle-induced oxidative stress. The lower antioxidative capability of mammary glands, combined with the TNP-induced oxidative stress suggested the possibility of tissue injury in the mammary glands of lactating dams.


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)

Determination of levels of MDA (A), GSH (B), Linear correlation between dose and MDA in mammary gland (C) and comparison of TNP generated oxidative stress in mammary glands and liver (D) at LD 10 after four doses of TNP exposures (8 mg/kg) at LDs 2, 4, 6 and 8.Seven mice in each group were examined. Data are mean±s.d. (n = 7 per group). Values in "" are hypothetical values when the internal dose in mammary gland were 1000 μg Ti/g tissue. The symbol * represents significant difference from the PBS group (P<0.05). ΔMDA = (Liver MDA in TNP groups)–(Liver MDA in PBS groups). . ΔGSH and GSH per 1000 μg were obtained similarly.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122591.g003: Determination of levels of MDA (A), GSH (B), Linear correlation between dose and MDA in mammary gland (C) and comparison of TNP generated oxidative stress in mammary glands and liver (D) at LD 10 after four doses of TNP exposures (8 mg/kg) at LDs 2, 4, 6 and 8.Seven mice in each group were examined. Data are mean±s.d. (n = 7 per group). Values in "" are hypothetical values when the internal dose in mammary gland were 1000 μg Ti/g tissue. The symbol * represents significant difference from the PBS group (P<0.05). ΔMDA = (Liver MDA in TNP groups)–(Liver MDA in PBS groups). . ΔGSH and GSH per 1000 μg were obtained similarly.
Mentions: The generation of oxidative stress by nanomaterials is suggested to be one of the main reasons for nanoparticle-induced tissue damages in testis [19], brain [27, 37], liver [38, 39], placenta and fetuses [18, 40]. Moreover, neutrophil-induced oxidative stress was found to damage mammary gland tissues in animals with mastitis (inflammation of the breast) [41, 42]. The accumulation of TNPs in lactating mammary glands suggested that TNPs might generate local oxidative stress. To evaluate the oxidative stress level in mammary glands, we analyzed the concentrations of two oxidative stress markers, malondialdehyde (MDA) and glutathione (GSH), in mammary glands. The exposure of the dams to TNP-8 and TNP-50 at 8 mg/kg increased the MDA level and decreased the GSH level in mammary glands (Fig 3A and 3B). The mammary glands exhibited a considerably lower antioxidative capability than the liver, as indicated by a comparison of the net increases in MDA and decreases in GSH in mammary glands and liver when the internal doses of TNPs were normalized to the same value (Fig 3C). As shown in Fig 3C, the TNP-induced oxidative stress in mammary glands would be 15–130 times higher than that in the liver if the internal dose were normalized to the same level. This indicated that mammary glands were more vulnerable to nanoparticle-induced oxidative stress. The lower antioxidative capability of mammary glands, combined with the TNP-induced oxidative stress suggested the possibility of tissue injury in the mammary glands of lactating dams.

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