Nutraceutical Effect of Resveratrol on the Mammary Gland: Focusing on the NF-κb /Nrf2 Signaling Pathways

SIMPLE SUMMARY: It is essential to study animal models of human disease to understand the progression of disease, the mechanisms involved and their interventional testing on a pre-clinical basis. We proposed to observe a lipopolysaccharide (LPS)-induced effective model of mammary gland inflammation. Additionally, the nutraceutical role of resveratrol, a phenolic compound, against the negative effects of lipopolysaccharides (LPS) in mammary tissues caused by oxidative damage and inflammation has not been fully studied. In our experiments, we found that LPS significantly enhances oxidative stress by repressing the expression of oxidative-related factors and stimulating the secretion of inflammatory cytokines. Moreover, LPS decreases the body weight, water and feed intake and activates NF-κB, Jnk, Erk, and Nrf2. The relative protein intensity of P65 and pP65 were increased by LPS. However, resveratrol administration remarkably decreases the oxidative response as well as inflammatory genes and plays a vital role in protection of the mammary glands from negative alterations in female mice. ABSTRACT: The aim of this study is to evaluate the defensive role of resveratrol, which is antagonistic to the oxidative stress and inflammation that is prompted by LPS in mammary tissue of female mice. Thirty adult mice were distributed into three groups (n = 10) control (CON), lipopolysaccharides at 2.5 mg/kg (LPS), and lipopolysaccharides at 2.5 mg/kg with 2 mg/kg of resveratrol (RES + LPS). The treatments were applied for 15 consecutive days. Spectrophotometry was used to quantify ROS in the blood, and proinflammatory cytokines concentrations were determined through radioimmunoassay. NF-κB, Jnk, IL-1β, Erk, IL-6, Nrf2 and TNF-α were quantified by RT-qPCR, and Western blots were used to quantifyP65 and pP65 protein intensities. MDA production was considerably increased, and the activity of T-AOC declined in the LPS treatment in comparison with the CON group but was significantly reversed in the RES + LPS group. Proinflammatory cytokines production and the genes responsible for inflammation and oxidative stress also showed higher mRNA and pP65 protein intensity in the LPS group, while Nrf2 showed a remarkable decline in mRNA expression in the LPS versus the CON group. All these mRNA intensities were reversed in the RES + LPS group. There were no remarkable changes in P65 protein intensity observed between the CON, LPS, and RES + LPS groups. In conclusion, resveratrol acts as a protective agent to modulate cellular inflammation and oxidative stress caused by LPS in mammary tissue of female mice.