The Combined Anti-inflammatory Strategy of Beta-2 Adrenergic Agonist and Glucocorticoid on the Laying Hen Model of Ovarian Cancer: the Immune Traits and Ovarian Inflammatory Functions

Abstract

Background: Ovarian cancer known as one of the most lethal gynecological malignancies mainly in older women, has been documented to link with chronic inflammation. Objective: This study was aimed to evaluate the combined strategy of glucocorticoid (GC) Fluticasone and beta-2 adrenergic agonist (BAA) Salmeterol on the ovarian inflammatory functions of the laying hen as a model of women ovarian cancer. Methods: White Leghorn hens aged 92 weeks were used for four weeks to be supplemented by individual of GC and BAA administration and their combination at three ratios GC:BAA 1:4 (GC+BAA1), 1:2 (GC+BAA2), and 1:1 (GC+BAA3), and beta blocker (BB) Propranolol. Ovulation rate and follicular growth were determined based on laying frequency and visual evaluation, respectively, the mRNA expressions of follicular beta-2 adrenergic receptor (β2ADR), cyclooxygenases (COX) 1 and 2, and cytokines were measured by real-time PCR. The plasma concentration of ovarian hormones cellular and humoral immune responses were measured via ELISA, neutrophil (heterophil) to lymphocyte ratio (NLR), and sheep red blood cell (SRBC) test, respectively. Results: As compared to control, combination groups of GC+BAA1 and 2 brought about a significant decrease in the mRNA expression of β2ADR, COX-2, and cytokines (P< 0.05). The ovulation rate was reduced in all combination ratios (P< 0.05). A significant reduction was observed in the plasma estradiol content on GC+BAA groups (P< 0.05) and the content of progesterone and androgen were statistically similar in some of these groups. Although NLR was similar in GC+BAA2 and 3, these groups had more content in the whole immunoglobulin (Ig) and IgM (P< 0.05). The results indicated that body weight and food consummation were decreased in all of the combination groups (P< 0.05). Conclusion: The GC and BAA combination may result in a significant reduction in some of the boosting factors on ovarian cancer, like ovulation intensity, pro-inflammatory mediators, and some of the ovarian steroid hormones that could define as the therapeutic approaches for the chronic inflammation-based carcinomas like ovarian cancer.