The effects of liraglutide on the characteristics of blood parameters and testicular tissue induced diabetes and obesity in mice

Mohammadzadeh, Saied; Amiri, Mosayeb

doi:10.61186/JBUMS.31.2.150

Volume 31, Issue 2 (July 2024) J Birjand Univ Med Sci. 2024, 31(2): 150-160 | Back to browse issues page

‎ 10.61186/JBUMS.31.2.150

Research code: 1400.12

Ethics code: LU.ECRA.2023.52

Clinical trials code: testnew for site

Mendeley

Zotero

RefWorks

Mohammadzadeh S, Amiri M. The effects of liraglutide on the characteristics of blood parameters and testicular tissue induced diabetes and obesity in mice. J Birjand Univ Med Sci. 2024; 31 (2) :150-160
URL: http://journal.bums.ac.ir/article-1-3400-en.html

The effects of liraglutide on the characteristics of blood parameters and testicular tissue induced diabetes and obesity in mice

Saied Mohammadzadeh ^*¹

, Mosayeb Amiri²

1- Department of Animal Science, Faculty of Agriculture, Lorestan University, Khoramabad, Iran , Mohammadzadeh.s@lu.ac.ir
2- Department of Animal Science, Faculty of Agriculture, Lorestan University, Khoramabad, Iran

Abstract: (734 Views)

Background and Aims: Obesity and diabetes are the most common metabolic disorders that have negative effects on organisms, including the reproductive system. The drug treatments cause fertility disorders. One of the candidate drugs is liraglutide. The present study sought to assess the effect of liraglutide on testicular tissue and blood parameters, especially C-reactive protein (inflammation index).
Materials and Methods: A total of 40 adult male mice were assigned to five groups with eight replications. These groups included control, obese, obese+liraglutide injected 1.2 mg/kg of body weight, diabetes, and the last group, diabetes+liraglutide injected 1.2 mg/kg of body weight. Liraglutide was injected subcutaneously daily. The duration of the experiment was six weeks. After the end of the experiment, the animals were anesthetized, and blood samples and testicular sections were taken. Animals were euthanized (cervical dislocation). The testicles were removed and fixed. The tissue sections were prepared according to the usual protocol.
Results: The results demonstrated that the diameter of seminiferous tubules in obese and diabetic groups was increased by liraglutide injection (P<0.01). Diabetes and obesity decreased the thickness of the germ cell epithelium of seminiferous tubules (P<0.01). The C-reactive protein decreased in diabetic and obese groups when injected with liraglutide (P<0.01).
Conclusion: As evidenced by the results obtained, liraglutide can improve the male reproductive system and reduce chronic inflammation caused by obesity and diabetes.

Keywords: Diabetes, Liraglutide, Mice, Obesity, Testis

Full-Text [PDF 598 kb] (345 Downloads) | | Full-Text (HTML) (137 Views)

Type of Study: Original Article | Subject: Physiology
Received: 2024/03/17 | Accepted: 2024/06/29 | ePublished ahead of print: 2024/06/30 | ePublished: 2024/08/5

References

1. Jalaba S, Trudeau H, Carlson S. Obesity Prevention. Physician Assistant Clinics. 2022; 7(1): 43-58. DOI: 10.1016/j.cpha.2021.07.004. [DOI:10.1016/j.cpha.2021.07.004]

2. Leech CA, Dzhura I, Chepurny OG, Kang G, Schwede F, Genieser H-G, et al. Molecular physiology of glucagon-like peptide-1insulin secretagogue action in pancreatic β cells. Prog. Biophys Mol Biol. 2011; 107(2): 236-47. DOI: 10.1016/j.pbiomolbio.2011.07.005. [DOI:10.1016/j.pbiomolbio.2011.07.005]

3. Lim AK. Diabetic nephropathy-complications and treatment. Int J Nephrol Renovasc Dis. 2014; 7: 361-81. DOI: 10.2147/IJNRD.S40172. [DOI:10.2147/IJNRD.S40172]

4. Khavarimehr M, Nejati V, Razi M, Najafi Gh. Ameliorative effect of omega-3 on spermatogenesis, testicular antioxidant status and preimplantation embryo development in streptozotocin-induced diabetes in rats. Int Urol Nephrol. 2017; 49(9): 1545-60. DOI: 10.1007/s11255-017-1636-5. [DOI:10.1007/s11255-017-1636-5]

5. Glazer CH, Bonde JP, Giwercman A, Vassard D, Pinborg A, Schmidt L, et al. Risk of diabetes according to male factor infertility: a register-based cohort study. Hum Reprod. 2017; 32(7): 1474-81. DOI: 10.1093/humrep/dex097. [DOI:10.1093/humrep/dex097]

6. Eftekhari S, Montazeri H, Tarighi PJEJoP. Synergistic anti-tumor effects of Liraglutide, a glucagon-like peptide-1 receptor agonist, along with Docetaxel on LNCaP prostate cancer cell line. Eur J Pharmacol. 2020; 878: 173102. DOI: 10.1016/j.ejphar.2020.173102. [DOI:10.1016/j.ejphar.2020.173102]

7. Khalily R, Hasanzadeh S, Shalizar Jalali A, Shahrooze R, Nagafi G, Imani M. The Effects of Liraglutide on In Vitro Fertilization in Mice Following Experimental Diabetes. Qom Univ Med Sci J 2020; 14 (1): 51-60 URL: http://journal.muq.ac.ir/article-1-2619-en.html DOI: 10.29252/qums.14.1.51 [Persian]. [DOI:10.29252/qums.14.1.51]

8. Puyamanesh zahra YP, Ebrahin Habibi Azadeh, Mohammad Amoli Azadeh. Biochemical Effects of Fructose Diet on Obesity in Adult Male NMRI Mice. Food technology and nutrition. 2016; 13(1): 47-54. URL: https://sanad.iau.ir/Journal/jftn/Article/832520 [Persian].

9. Deng C, Cao J, Han J, Li J, Li Z, Shi N, et al. Liraglutide activates the Nrf2/HO-1 antioxidant pathway and protects brain nerve cells against cerebral ischemia in diabetic rats. Comput Intell Neurosci. 2018; 2018: 3094504. DOI: 10.1155/2018/3094504. [DOI:10.1155/2018/3094504]

10. Kabel AMJB, Pharmacotherapy. Zinc/alogliptin combination attenuates testicular toxicity induced by doxorubicin in rats: Role of oxidative stress, apoptosis and TGF-β1/NF-κB signaling. Biomed Pharmacother. 2018; 97: 439-49. DOI: 10.1016/j.biopha.2017.10.144. [DOI:10.1016/j.biopha.2017.10.144]

11. Vargas-Soria M, Carranza-Naval MJ, Del Marco A, Garcia-Alloza MJAsr, therapy. Role of liraglutide in Alzheimer's disease pathology. Alzheimer's Res Ther. 2021; 13(1): 112. DOI: 10.1186/s13195-021-00853-0 [DOI:10.1186/s13195-021-00853-0]

12. Yang C-C, Chen Y-T, Chen C-H, Chiang JY, Zhen Y-Y, Yip H-KJAJoTR. Assessment of doxorubicin-induced mouse testicular damage by the novel second-harmonic generation microscopy.Am J Transl Res. 2017; 9(12): 5275-88. URL: https://pubmed.ncbi.nlm.nih.gov/29312482. PMCID: PMC5752880

13. Alafifi SA, Wahdan SA, Elhemiely AA, Elsherbiny DA, Azab SSJN-SsAoP. Modulatory effect of liraglutide on doxorubicin-induced testicular toxicity and behavioral abnormalities in rats: role of testicular-brain axis. Naunyn Schmiedeberg's Arch Pharmacol. 2023; 396(11): 2987-3005. DOI: 10.1007/s00210-023-02504-7 [DOI:10.1007/s00210-023-02504-7]

14. Hany A, Doaa A, ATTIA M, Mohammed A. Effect of glucagon like peptide-1 on serum kisspeptin level in adult male albino rats treated by anabolic androgenic steroid. Med J Cairo Univ. 2018; 86(June): 1431-45. DOI: 10.21608/MJCU.2018.56345. [DOI:10.21608/mjcu.2018.56345]

15. Ateşşahin A, Karahan İ, Yılmaz S, Çeribaşı AO, Bulmuş ÖJF, sterility. Lycopene prevents adriamycin-induced testicular toxicity in rats. Fertil Steril; 2006: 85 Suppl 1: 1216-22. DOI: 10.1016/j.fertnstert.2005.11.035 [DOI:10.1016/j.fertnstert.2005.11.035]

16. Prahalathan C, Selvakumar E, Varalakshmi PJRT. Lipoic acid modulates adriamycin-induced testicular toxicity. Reprod Toxicol. 2006; 21(1): 54-9. DOI: 10.1016/j.reprotox.2005.07.002. [DOI:10.1016/j.reprotox.2005.07.002]

17. Jensterle M, Podbregar A, Goricar K, Gregoric N, Janez AJEc. Effects of liraglutide on obesity-associated functional hypogonadism in men. Endocr Connect. 2019; 8(3): 195-202. DOI: 10.1530/EC-18-0514 [DOI:10.1530/EC-18-0514]

18. Caltabiano R, Condorelli D, Panza S, Boitani C, Musso N, Ježek D, et al. Glucagon‐like peptide-1 receptor is expressed in human and rodent testis. Androl. 2020; 8(6): 1935-45. DOI: 10.1111/andr.12871. [DOI:10.1111/andr.12871]

19. Safrazadeh A, Ghrakhanloo R, Hedayati M, Talebigorgani E. The Effect of 4 Weeks Resistance Training on Serum Vaspin, Il-6, CRP and TNF-Α Concentrations in Diabetic Rats. Iranian J Endocrinol Metab. 2012; 14(1): 68-74. URL: http://ijem.sbmu.ac.ir/article-1-1244-en.html. [Persian].

20. Ahmed ZA, Abtar AN, Othman HH, Aziz TA. Effects of quercetin, sitagliptin alone or in combination in testicular toxicity induced by doxorubicin in rats. Drug Des Devel Ther. 2019; 20: 13: 3321-29. DOI: 10.2147/DDDT.S222127. [DOI:10.2147/DDDT.S222127]

21. Malekinejad H, Janbaz-Acyabar H, Razi M, Varasteh SJP. Preventive and protective effects of silymarin on doxorubicin-induced testicular damages correlate with changes in c-myc gene expression. Phytomedicine. 2012; 19(12): 1077-84. DOI: 10.1016/j.phymed.2012.06.011. [DOI:10.1016/j.phymed.2012.06.011]

22. Milani L, Galindo CM, de Oliveira NMT, Corso CR, Adami ER, Stipp MC, et al. The GLP-1 analog liraglutide attenuates acute liver injury in mice. Ann Hepatol. 2019; 18(6): 918-28. DOI: 10.1016/j.aohep.2019.04.011. [DOI:10.1016/j.aohep.2019.04.011]

23. Degirmentepe RB, Altunrende F, Bozkurt M, Merder E, Otunctemur A, Sonmez K, et al. Protective effect of liraglutide on experimental testicular ischaemia reperfusion in rats. Andrologia. 2021; 53(4): e14000. DOI: 10.1111/and.14000 [DOI:10.1111/and.14000]

24. Tian Y, Song W, Xu D, Chen X, Li X, Zhao Y, et al. Autophagy induced by ROS aggravates testis oxidative damage in diabetes via breaking the feedforward loop linking p62 and Nrf2. Oxid Med Cell Longev. 2020; 18: 2020: 7156579. DOI: 10.1155/2020/7156579. [DOI:10.1155/2020/7156579]

25. Long L, Qiu H, Cai B, Chen N, Lu X, Zheng S, et al. Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget. 2018; 9(4): 5321-36. DOI: 10.18632/oncotarget.23915. [DOI:10.18632/oncotarget.23915]

26. Abbas NA, Kabil SL. Liraglutide ameliorates cardiotoxicity induced by doxorubicin in rats through the Akt/GSK-3β signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2017; 390(11): 1145-53. DOI: 10.1007/s00210-017-1414-z. [DOI:10.1007/s00210-017-1414-z]

27. Zhang Y, Yan H, Xu Z, Yang B, Luo P, He Q, et al. Molecular basis for class side effects associated with PI3K/AKT/mTOR pathway inhibitors. Expert Opin Drug Metab Toxicol. 2019; 15(9): 767-74. DOI: 10.1080/17425255.2019.1663169. [DOI:10.1080/17425255.2019.1663169]