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Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland.


ABSTRACT: The aim of this study was to investigate the mechanisms underlying the reduced milk production during mastitis. We hypothesized that bacterial endotoxin induces hypoxia, oxidative stress, and cell apoptosis while inhibiting milk gene expression in the mammary gland. To test this hypothesis, the left and right sides of the 4th pair of mouse mammary glands were alternatively injected with either lipopolysaccharide (LPS, E. coli 055: B5, 100??L of 0.2?mg/mL) or sterile PBS through the teat meatus 3 days postpartum. At 10.5 and 22.5?h postinjection, pimonidazole HCl, a hypoxyprobe, was injected intraperitoneally. At 12 or 24?h after the LPS injection, the 4th glands were individually collected (n = 8) and analyzed. LPS treatment induced mammary inflammation at both 12 and 24?h but promoted cell apoptosis only at 12?h. Consistently, H2O2 content was increased at 12?h (P < 0.01), but dropped dramatically at 24?h (P < 0.01) in the LPS-treated gland. Nevertheless, the total antioxidative capacity in tissue tended to be decreased by LPS at both 12 and 24?h (P = 0.07 and 0.06, respectively). In agreement with these findings, LPS increased or tended to increase the mRNA expression of antioxidative genes Nqo1 at 12?h (P = 0.05) and SLC7A11 at 24?h (P = 0.08). In addition, LPS inhibited mammary expression of Csn2 and Lalba across time and protein expression of Csn1s1 at 24?h (P < 0.05). Furthermore, hypoxyprobe staining intensity was greater in the alveoli of the PBS-treated gland than the LPS-treated gland at both 12 and 24?h, demonstrating a rise in oxygen tension by LPS treatment. In summary, our observations indicated that while intramammary LPS challenge incurs inflammation, it induces oxidative stress, increases cell apoptosis and oxygen tension, and differentially inhibits the milk protein expression in the mammary gland.

SUBMITTER: Spitzer AJ 

PROVIDER: S-EPMC7128054 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Bacterial Endotoxin Induces Oxidative Stress and Reduces Milk Protein Expression and Hypoxia in the Mouse Mammary Gland.

Spitzer Alexander Jonathan AJ   Tian Qing Q   Choudhary Ratan K RK   Zhao Feng-Qi FQ  

Oxidative medicine and cellular longevity 20200324


The aim of this study was to investigate the mechanisms underlying the reduced milk production during mastitis. We hypothesized that bacterial endotoxin induces hypoxia, oxidative stress, and cell apoptosis while inhibiting milk gene expression in the mammary gland. To test this hypothesis, the left and right sides of the 4<sup>th</sup> pair of mouse mammary glands were alternatively injected with either lipopolysaccharide (LPS, <i>E. coli</i> 055: B5, 100 <i>μ</i>L of 0.2 mg/mL) or sterile PBS  ...[more]

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