Phosphodiesterase inhibitor Theophylline in the aged laying hens: investigation of the ovarian and fallopian inflammatory mediators, hormones, and functions

Document Type : Original Research Article (Regular Paper)

Authors

1 Department of Animal Science, Sari Agricultural Sciences and Natural Resources University, Postal Code: 48181-66996, Sari, Iran

2 Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Postal Code: 77871-3158,7Karaj, Iran

Abstract

Inflammatory-dependent events in the aged commercial laying hens reduce production rate and egg quality. Our study was aimed to evaluate the phosphodiesterase (PDE) inhibitor Theophylline on the ovarian and fallopian-inflammatory traits in the commercial laying hens at the late stage of the production period. Twenty-four White Leghorn hens aged 92 weeks were used for four weeks to be orally supplemented by Theophylline (3 mg/kg/Body weight, BW). Ovulation rate and follicular growth were measured by laying frequency and, visual evaluation after euthanizing, respectively. The mRNA expressions of follicular and fallopian cyclooxygenases 1 and 2 (COX-1,-2), and cytokines were detected by real-time PCR. Plasma concentrations of ovarian hormones (Two hours after lighting) were measured via enzyme-linked immunosorbant assay (ELISA). The results showed that the mRNA expression of the IL-1β, IL-6 and TNF-α in the ovary and IL-1β and TNF-α in the infundibulum were significantly decreased (P<0.01) by Theophylline treatment; however, the mRNA abundance of COX-2 and IL-10 in both of ovary and infundibulum were increased (P<0.01). Plasma concentrations of estradiol and progesterone were elevated (P<0.05) in the hens treated with Theophylline. Ovulation rate and follicular size were not significantly (P>0.05) influenced by Theophylline. As a phosphodiesterase inhibitor, Theophylline retained the laying frequency in addition to enhancing its anti-inflammatory capability in the late stage of production period in laying hens.

Keywords

Main Subjects


l advice during the farm stage of this study.
 
References
Amer, S., 2007. Gonadotropin induction of ovulation. Obstetrics, Gynaecology and Reproductive Medicine 17, 205-210.
Apperson, K.D., Bird, K.E., Cherian, G.,  Löhr, C.V., 2017. Histology of the ovary of the laying hen (Gallus domesticus). Veterinary Sciences 4, 66.
Barnes, P.J., 2006. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. British Journal of Pharmacology 148, 245-254.
Barnes, P.J. 2013. Theophylline. American Journal of Respiratory and Critical Care Medicine 188, 901-906.
Barua, A., Bradaric, M.J., Bitterman, P., Abramowicz, J.S., Sharma, S., Basu, S., Lopez, H.,  Bahr, J.M. 2013. Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer. American Journal of Reproductive Immunology 70, 538-50.
Breuiller, M., Tahri-Joutei, A., Ferré, F., Pointis, G., 1988. β-Adrenergic receptors and stimulatory effects of (−) isoproterenol on testosterone   production in fetal mouse leydig cells. Biochemical and Biophysical Research Communications 151, 1454-1460.
Buriani, A., Fortinguerra, S. Carrara, M., 2017. Clinical perspectives in diagnostic-omics and personalized medicine approach to monitor effectiveness and toxicity of phytocomplexes. Pelkonen, O., Duez, P., Vuorela, P.M., Vuorela, H., Toxicology of Herbal Products., Springer International Publishing, Cham, pp. 385-476.
Ebeid, T.A., Eid, Y.Z., El-Abd, E.A. & El-Habbak, M.M., 2008. Effects of catecholamines on ovary morphology, blood concentrations of Estradiol-17β, Progesterone, zinc, triglycerides and rate of ovulation in domestic hens. Theriogenology 69, 870-876.
Eid, N.S., O'hagan, A., Bickel, S., Morton, R., Jacobson, S., Myers, J.A., 2016. Anti-inflammatory dosing of theophylline in the treatment of status asthmaticus in children. Journal of Asthma and Allergy  9, 183-189.
Elhamouly, M., Isobe, N., Yoshimura, Y., 2017. Expression and localization of cyclooxygenases in the oviduct of laying hens during the ovulatory cycle. Theriogenology 101, 1-7.
Elnagar, S.A., Khalil, H.M., El-Sheikh, A., 2002. Estradiol and Progesterone levels during an ovulatory cycle of two local strains of laying hens. Egyptian Poultry Science 22, 869-878.
Emori, M.M., Drapkin, R., 2014. The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis. Reproductive Biology and Endocrinology 12, 60.
Fleming, J.S., Beaugié, C.R., Haviv, I., Chenevix-Trench, G., Tan, O.L., 2006. Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Molecular and Cellular Endocrinology 247, 4-21.
Ghasemi-Pirbaluti, M., Motaghi, E., Najafi, A., Hosseini, M.J., 2017. The effect of Theophylline on acetic acid induced ulcerative colitis in rats. Biomedicine & Pharmacotherapy, 90, 153-159.
Hales, D.B., Zhuge, Y., Lagman, J.A.J., Ansenberger, K., Mahon, C., Barua, A., Luborsky, J.L. Bahr, J.M., 2008. Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus). Endocrine 33, 235-244.
Hashemi- Niasari, F., Rabbani-Chadegani, A., Razmi, M., Fallah, S., 2018. Synergy of Theophylline reduces necrotic effect of berberine, induces cell cycle arrest and PARP, HMGB1, Bcl-2 family mediated apoptosis in MDA-MB-231 breast cancer cells. Biomedicine & Pharmacotherapy 106, 858-867.
Hatefi, A., Zare Shahneh, A., Ansari Pirsaraie, Z., Alizadeh, A.M., Atashnak, M.P., Masoudi, R., Pio, F., 2021. The stimulation and inhibition of beta-2 adrenergic receptor on the inflammatory responses of ovary and immune system in the aged laying hens. BMC Veterinary Research, 17(1), 195.
He, H., Chen, F., Ni, W., Li, J., Zhang, Y., 2014. Theophylline improves Lipopolysaccharide-induced alveolarization arrest through inflammatory regulation. Molecular Medicine Reports 10, 269-275.
Holesh, J.E., Bass, A.N., Lord, M., 2020. Physiology, Ovulation. In: StatPearls. StatPearls Publishing, Treasure Island (FL); 2022. PMID: 28723025.USA.
Iiboshi, H., Ashitani, J.I., Katoh, S., Sano, A., Matsumoto, N., Mukae, H., Nakazato, M., 2007. Long-term treatment with Theophylline reduces neutrophils, interleukin-8 and tumor necrosis factor-α in the sputum of patients with chronic obstructive pulmonary disease. Pulmonary Pharmacology & Therapeutics 20, 46-51.
Jeon, S.Y., Hwang, K.A., Choi, K.C., 2016. Effect of steroid hormones, Estrogen and Progesterone, on epithelial mesenchymal transition in ovarian cancer development. The Journal of Steroid Biochemistry and Molecular Biology 158, 1-8.
Jilani, T.N., Preuss, C.V., Sharma, S., Theophylline. 2022. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30085566, USA
 Johnson, P.A., Giles, J.R., 2013. The hen as a model of ovarian cancer. Nature Reviews Cancer 13, 432-436.
Juergens, U.R., Degenhardt, V., Stöber, M., Vetter, H., 1999. New insights in the bronchodilatory and anti-inflammatory mechanisms of action of Theophylline. Arzneimittelforschung 49, 694-698.
Karst, A.M., Drapkin, R., 2010. Ovarian cancer pathogenesis: a model in evolution. Journal of Oncology 2010, 932371.
Klein, T., Shephard, P., Kleinert, H., Kömhoff, M., 2007. Regulation of cyclooxygenase-2 expression by cyclic AMP. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1773, 1605-1618.
Kollmann, Z., Schneider, S., Fux, M., Bersinger, N.A., Von Wolff, M., 2017. Gonadotrophin stimulation in IVF alters the immune cell profile in follicular fluid and the cytokine concentrations in follicular fluid and serum. Human Reproduction 32, 820-831.
Liu, J.H., Durfee, R., Muse, K., Yen, S.S.C., 1983. Induction of multiple ovulation by pulsatile administration of gonadotropin-releasing hormone. Fertility and Sterility 40, 18-22.
Livak, K.J., Schmittgen, T.D., 2001. Analysis of relative gene expression data using real-time quantitative pcr and the 2−ΔΔCT method. Methods 25, 402-408.
Macciò, A., Madeddu, C., 2012. Inflammation and ovarian cancer. Cytokine 58, 133-147.
Mishra, B., Sah, N., Wasti, S., 2019. Genetic and hormonal regulation of egg formation in the oviduct of laying hens. Poultry-An Advanced Learning. DOI: 10.5772/intechopen.85011
Mitani, T., Takaya, T., Harada, N., Katayama, S., Yamaji, R., Nakamura, S., Ashida, H., 2018. Theophylline suppresses interleukin-6 expression by inhibiting glucocorticoid receptor signaling in pre-adipocytes. Archives of Biochemistry and Biophysics 646, 98-106.
Nakada, T., Koja, Z., Tanaka, K., 1994. Effect of progesterone on ovulation in the hypophysectomised hen. British Poultry Science 35, 153-156.
Pal, P., Hales, K., Petrik, J., Hales, D.B., 2019. Pro-apoptotic and anti-angiogenic actions of 2-methoxy estradiol and docosahexaenoic acid, the biologically derived active compounds from flaxseed diet, in preventing ovarian cancer. Journal of Ovarian Research 12, 1-16.
Peng, H., Su, Q., Lin, Z.C., Zhu, X. H., Peng, M.S.,  Lv, Z.B., 2018. Potential suppressive effects of theophylline on human rectal cancer SW480 cells in vitro by inhibiting YKL-40 expression. Oncology Letters 15, 7403-7408.
Qi, X., Tan, D., Wu, C., Tang, C., Li, T., Han, X., Wang, J., Liu, C., Li, R., Wang, J., 2016. Deterioration of eggshell quality in laying hens experimentally infected with H9N2 avian influenza virus. Veterinary Research 47, 1-10.
Redshaw, M., Follett, B., 1972. The physiology of egg yolk production in the hen. Egg Formation and Production 8, 35-50.
Sevoian, M., Levine, P.P., 1957. Effects of infectious bronchitis on the reproductive tracts, egg production, and egg quality of laying chickens. Avian Diseases 1, 136-164.
Straub, R.H., 2007. The complex role of estrogens in inflammation. Endocrine Reviews 28, 521-574.
Swartz, S.R., Moberg, G.P., 1986. Effects of epinephrine, norepinephrine, and dopamine on gonadotropin-releasing hormone-induced secretion of luteinizing hormone in vitro. Endocrinology 118, 2425-2431.
Terlikowska, K., Dobrzycka, B., Terlikowski, S., 2018. Ovarian cancer and inflammation. Part 2. Anti-inflammatory cytokines. Progress in Health Sciences 8, 206-209.
Traish, A., Bolanos, J., Nair, S., Saad, F., Morgentaler, A., 2018. Do androgens modulate the pathophysiological pathways of inflammation? Appraising the contemporary evidence. Journal of Clinical Medicine 7, 549 (1-33).
Tsukagoshi, H., Shimizu, Y., Iwamae, S., Hisada, T., Ishizuka, T., Iizuka, K., Dobashi, K., Mori, M., 2000. Evidence of oxidative stress in asthma and COPD: potential inhibitory effect of theophylline. Respiratory Medicine 94, 584-588.
Unsicker, K., Seidel, F., Hofmann, H.D., Müller, T., Schmidt, R., Wilson, A., 1983. Catecholaminergic innervation of the chicken ovary. Cell and Tissue Research 230, 431-450.
Urick, M.E., Giles, J.R., Johnson, P A., 2009. Dietary aspirin decreases the stage of ovarian cancer in the hen. Gynecologic Oncology 112, 166-70.
Zhang, X., Liao, K., Chen, S., Yan, K., Du, X., Zhang, C., Guo, M., Wu, Y., 2020. Evaluation of the reproductive system development and egg-laying performance of hens infected with TW I-type infectious bronchitis virus. Veterinary Research 51, 95.
Zhou, Z., Bian, C., Luo, Z., Guille, C., Ogunrinde, E., Wu, J., Zhao, M., Fitting, S., Kamen, D.L.,  Oates, J. C., 2019. Progesterone decreases gut permeability through upregulating Occludin expression in primary human gut tissues and Caco-2 cells. Scientific Reports 9, 1-13.