Potential effects of incretin-based therapies on polycystic ovary syndrome in rats: a comparative study of linagliptin versus liraglutide

Hanan Abdelmoneam Shamardl (1) , Hala Fawzy Kamel (2) , Asmaa Mohamed Elsayed (3) , Hiba Saeed Al-Amodi (4) , Sahar Mohy El-Ashmony (5)
(1) Department of Medical Pharmacology, Faculty of Medicine, Fayoum University, Fayoum 19052, Egypt, Egypt ,
(2) Department of Medical Biochemistry, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt, Egypt ,
(3) Department of Histology, Faculty of Medicine, Fayoum University, Fayoum, 19052, Egypt, Egypt ,
(4) Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia, Saudi Arabia ,
(5) Department of Medical Pharmacology Faculty of Medicine, Cairo University, Cairo, Egypt, Egypt

Abstract

Low glucagon like peptide1 (GLP-1) level may contribute to the metabolic dysfunction in polycystic ovary syndrome (PCOS).  In this study, prospective therapeutic effects of incretin-based drugs; linagliptin versus liraglutide were investigated on letrozole induced PCOS rats. Animals were divided into five groups (control, PCOS, linagliptin, liraglutide and combined). Letrozole was administered for seven weeks (1mg/kg/day, orally). Linagliptin (3mg/kg/day, orally), liraglutide (1.2mg/kg/day, Sc) and combined drugs were given for 4 weeks. Measurements of anthropometric, hemodynamics, blood glucose indices, HOMA-IR, serum lipids, TNF-α, NF-kB, and sex hormones were estimated. Antioxidant activities alongside immunohistochemical (PCNA) studies were assessed. The present results proved that both drugs significantly ameliorated most of anthropometric, glycemic, lipid, hormonal, inflammatory and antioxidant indices. Obvious histological improvement was obtained by linagliptin and combined therapy while being questionable by liraglutide. In conclusion, linagliptin caused evident ovarian histological advance rather than liraglutide. Linagliptin may represent a promise in alleviating metabolic, hormonal and unique beneficial histologic effects of PCOS.

Full text article

Generated from XML file

References

Aebi, H. 1984. Catalase in vitro. Methods in Enzymology, 105:5016–5019.

AlSinan, A., Shaman, A. A. 2017. A Study to Measure the Health Awareness of Polycystic Ovarian Syndrome in Saudi Arabia. Global Journal of Health Science, 9(8):130.

Arakawa, M., Mita, T., et al. 2010. Inhibition of Monocyte Adhesion to Endothelial Cells and Attenuation of Atherosclerotic Lesion by a Glucagon-like Peptide-1 Receptor Agonist, Exendin-4.

Aroor, A. R., Habibi, J., et al. 2017. Dipeptidyl peptidase-4 (DPP-4) inhibition with linagliptin reduces western diet-induced myocardial TRAF3IP2 expression, inflammation and fibrosis in female mice. Cardiovascular Diabetology, 16(1):61–61.

Aydin, K., Arusoglu, G., et al. 2014. Fasting and post-prandial glucagon like peptide 1 and oral contraception in polycystic ovary syndrome. Clinical Endocrinology, 81(4):588–592.

Beloosesky, R., Gold, R., et al. 2004. Induction of polycystic ovary by testosterone in immature female rats: modulation of apoptosis and attenuation of glucose/insulin ratio. International journal of molecular medicine, 14(2):207–215.

Blech, S., Ludwig-Schwellinger, E., et al. 2010. The Metabolism and Disposition of the Oral Dipeptidyl Peptidase-4 Inhibitor, Linagliptin, in Humans. Drug Metabolism and Disposition, 38(4):667–678.

Boudreaux, M. Y., Talbott, E. O., et al. 2006. Risk of T2DM and impaired fasting glucose among pcos subjects: Results of an 8-year follow-up. Current Diabetes Reports, 6(1):77–83.

Deugarte, C., Bartolucci, A., Azziz, R. 2005. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertility and Sterility, 83(5):1454–1460.

Diamanti-Kandarakis, E., Papavassiliou, A. G. 2006. Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends in Molecular Medicine, 12(7):324–332.

Drucker, D. J., Nauck, M. A. 2006. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. The Lancet, 368(9548):1696–1705.

Eckardstein, A. V., Nieschlag, E., Behre, H. 1998. Androgens, cardiovascular risk factors and atherosclerosis. In In: Nieschlag E, Behre HM, editors. Testosterone: action, deficiency, substitution, pages 229–258, Berlin, Heidelberg, New York. Springer. 2nd Edition.

Elkind-Hirsch, K., Marrioneaux, O., Bhushan, M., Vernor, D., Bhushan, R. 2008. Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism, 93(7):2670–2678.

Escobar-Morreale, H. F., Millán, J. L. S. 2007. Abdominal adiposity and the polycystic ovary syndrome. Trends in Endocrinology & Metabolism, 18(7):266– 272.

Friedewald, W. T., Levy, R. I., Fredrickson, D. S. 1972. Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge. Clinical Chemistry, 18(6):499–502.

Frøssing, S., Nylander, M., et al. 2018. Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS. Endocrine Connections, 7(1):115–123.

Garber, A., Henry, R., et al. 2009. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. The Lancet, 373(9662):473–481.

González, F., Nair, K. S., Daniels, J. K., Basal, E., Schimke, J. M. 2012. Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women. American Journal of Physiology-Endocrinology and Metabolism, 302(3): E297–E306.

Holmang, A., Svedberg, J., Jennische, E., Bjorntorp, P. 1990. Effects of testosterone on muscle insulin sensitivity and morphology in female rats. American Journal of Physiology-Endocrinology and Metabolism, 259(4): E555–E560.

Ikegami, T., ichi Suzuki, Y., Koseki, H., et al. 2002. Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene.

Jahan, S., Munir, F., et al. 2016. Ameliorative effects of rutin against metabolic, biochemical and hormonal disturbances in polycystic ovary syndrome in rats. Journal of Ovarian Research, 9(1).

Jakubowicz, D., Barnea, M., Wainstein, J., Froy, O. 1979. Effects of caloric intake timing on insulin resistance and hyperandrogenism in lean women with polycystic ovary syndrome. Clinical Science, 125(9):423–432.

Janardhan, S., Sastry, G. 2014. Dipeptidyl Peptidase IV Inhibitors: A New Paradigm in Type 2 Diabetes Treatment. Current Drug Targets, 15(6):600–621.

Jashni, K. H., Jahromi, K. H., Bagheri, Z. 2016. The effect of palm pollen extract on polycystic ovary syndrome (POS) in rats. Int J Med Res Health Sci, 5(5):2319–5886.

Jensterle, M., Goricar, K., Janez, A. 2017. Add on DPP- 4 inhibitor alogliptin alone or in combination with pioglitazone improved β-cell function and insulin sensitivity in metformin treated PCOS. Endocrine Research, 42(4):261–268.

Jensterle, M., Kocjan, T., et al. 2015. Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome. Endocrine Research, 40(3):133–138.

Kabel, A. M., Al-Shehri, A. H., Al-Talhi, R. A., Elmaaboud, M. A. A. 2017. The promising effect of linagliptin and/or indole-3-carbinol on experimentally induced polycystic ovarian syndrome.

Kafali, H., Iriadam, M., Ozardalı, I., Demir, N. 2004. Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Archives of Medical Research, 35(2):103–108.

Kauffman, A. S., Thackray, V. G., et al. 2015. A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice. Biology of Reproduction, 93(3):69–69.

Khan, S., Priyamvada, S., et al. 2009. Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues. Food and Chemical Toxicology, 47(7):1562–1568.

Koibuchi, N., Hasegawa, Y., et al. 2014. DPP- 4 inhibitor linagliptin ameliorates cardiovascular injury in salt-sensitive hypertensive rats independently of blood glucose and blood pressure. Cardiovascular Diabetology, 13(1):157–157.

Meek, C. L., Bravis, V., et al. 2013. Polycystic ovary syndrome and the differential diagnosis of hyperandrogenism. The Obstetrician & Gynaecologist, 15(3):171–176.

Nestler, J. 2008. Metformin for the treatment of polycystic ovary syndrome. New England Journal of Medicine, 358(1):47–54.

Neumiller, J. J., Sonnett, T. E., et al. 2010. Pharmacology, efficacy and safety of liraglutide in the management of type 2 diabetes. Diabetes, metabolic syndrome and obesity: targets and therapy, 3:215– 226.

Nofal, E. A., El-Habeby, M. M., et al. 2019. Protective role of broccoli extract on estradiol valerate induced polycystic ovary syndrome in female rats. Eur J Anat, 23(2):121–129.

Palomba, S., Daolio, J., Sala, G. B. L. 2017. Oocyte Competence in Women with Polycystic Ovary Syndrome. Trends in Endocrinology & Metabolism, 28(3):186–198.

Pasquali, R., Gambineri, A. 2006. Insulin-sensitizing agents in women with polycystic ovary syndrome. Fertility and Sterility, 86(1): S28–S29.

Rajan, R. K., Kumar, M. S. S., Balaji, B. 2017. Soy isoflavones exert beneficial effects on letrozole induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism. Pharmaceutical Biology, 55(1):242–251.

Rezvanfar, M. A., Saeedi, S., et al. 2016. Dual targeting of TNF-αand free radical toxic stress as a promising strategy to manage experimental polycystic ovary. Pharmaceutical Biology, 54(1):80– 90.

Shi, D., Vine, D. F. 2012. Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk. Fertility and Sterility, 98(1):185–193.e2.

Terawaki, Y., Nomiyama, T., et al. 2015. Efficacy of dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes undergoing hemodialysis. Diabetology & Metabolic Syndrome, 7(1)

Vanessa Hoang, Bi, J., Mohankumar, S. M., Vyas, A. K. 2015. Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome. PLOS ONE, 10(5): e0126119–e0126119.

Walters, K. A., Allan, C. M., Handelsman, D. J. 2012. Rodent Models for Human Polycystic Ovary Syndrome1. Biology of Reproduction, 86(5):1–12.

Wood, R. 1997. Which DNA polymerases are used for DNA-repair in eukaryotes? Carcinogenesis, 18(4):605–610.

Zhang, M., Lv, X. Y., et al. 2008. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Experimental Diabetes Research, pages 704045–704045.

Zheng, L., Sun, Z., et al. 2008. Pulse Pressure and Mean Arterial Pressure in relation to Ischemic Stroke Among Patients with Uncontrolled Hypertension in Rural Areas of China. Stroke, 39(7):1932–1937.

Authors

Hanan Abdelmoneam Shamardl
hanan2remember@yahoo.com (Primary Contact)
Hala Fawzy Kamel
Asmaa Mohamed Elsayed
Hiba Saeed Al-Amodi
Sahar Mohy El-Ashmony
Hanan Abdelmoneam Shamardl, Hala Fawzy Kamel, Asmaa Mohamed Elsayed, Hiba Saeed Al-Amodi, & Sahar Mohy El-Ashmony. (2021). Potential effects of incretin-based therapies on polycystic ovary syndrome in rats: a comparative study of linagliptin versus liraglutide. International Journal of Research in Pharmaceutical Sciences, 12(2), 1044–1054. Retrieved from https://ijrps.com/home/article/view/77

Article Details

No Related Submission Found