VA inhibits LPS-induced oxidative stress via modulating Nrf2/NF-κB-signalling pathways in bovine mammary epithelial cells

• Main Authors: Huiyu Shi, Xiaoyu Guo, Sumei Yan, Yongmei Guo, Binlin Shi, Yanli Zhao
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: Italian Journal of Animal Science
• Subjects: vitamin a; interleukin-1; nrf2; nf-κb
• Online Access: http://dx.doi.org/10.1080/1828051X.2019.1619490
• ISSN: 1594-4077; 1828-051X

The current study was conducted to examine the pre-protection effects of vitamin A (VA) on lipopolysaccharide (LPS)-induced oxidative damage in bovine mammary epithelial cells (BMECs) and to explore the antioxidant mechanisms of VA via nuclear factor erythroid 2-related factor (Nrf2)/nuclear factor kappa-B (NF-κB)-signalling pathways. The BMECs were divided into 10 treatment groups with six replicates per treatment and were cultured with dimethyl sulphoxide (DMSO, vehicle negative control) or 0, 0.05, 0.1, 0.2, 0.5, 1, 2, 3, or 4 μg/mL of VA for 24 h and then incubated in the absence or presence of LPS (1 μg/mL) and VA for an additional 6 h. The results showed that exposure to LPS alone decreased the cell proliferation compared with the control. The addition of VA (from 0.05 to 4 μg/mL) promoted the proliferation of BMECs, and had positive effect on activities of glutathione peroxidase and its gene or protein expression but decreased NO and IL-1 production in a quadratic manner. Furthermore, VA significantly inhibited LPS-induced NF-κB activation and had a positive effect on Nrf2 activation in a quadratic dose-response manner and VA at a concentration of 1 μg/mL exhibited the strongest effect. The protective effect of VA dose greater than 2 μg/mL was weakened or even had no protective effect. These results suggest that VA pre-treatment protects BMECs from LPS-induced oxidative stress is due to Nrf2-signalling pathway activation and NF-κB-signalling pathway inhibition.Highlights VA protected against LPS-induced inflammatory cytokines IL-1β production on dose dependent manner quadraticlly, and the concentration of 1 μg/mL exhibited the strongest effect. VA significantly inhibited LPS-induced NF-κB activation and had a positive effect on Nrf2 activation in a quadratic dose-response manner. VA might be a valuable agent for the treatment of anti-inflammatory and antioxidant.