Document Type : Original Article

Authors

1 Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

2 Graduated from Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

3 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Abstract

Ischemia/reperfusion is one of the emergency cases that frequently occurs in testis. This pathologic event is one of the reasons for infertility in men. Inflammation and oxidative stress induce ischemia/reperfusion injury in testis. Consequently, agents possessing antioxidant activity are applied in the treatment of testicular ischemia/reperfusion. In the present study, the effect of berberine administration in the treatment of testicular ischemia/reperfusion injury is investigated. In this experiment, 24 Wistar rats were randomly divided into four groups (n = 6): Sham (receiving normal saline 0.9%), control (ischemia/reperfusion), treatment I (ischemia/reperfusion receiving 50 mg/kg berberine), and treatment II (ischemia/reperfusion receiving 100 mg/kg berberine). All injections were performed through the intraperitoneal route. Histopathological findings demonstrated that in the Sham group, testis has normal structure and normal spermatogenesis occurs. In the control group, severe hyperemia, coagulative necrosis, and interstitial edema are observed and spermatogenesis has severe damage. In treatment I group moderate interstitial edema, hyperemia, and coagulative necrosis are observed. Besides, spermatogenesis has moderate damage. In treatment II group all damages are mild. This experiment reveals that berberine exerts its protective impact in a dose-dependent manner so that the highest protective impact is observed in the group treated with 100 mg/kg of berberine. With respect to the major role of testicular ischemia in infertility and the results of the present study, berberine can be used as a valuable plant extract in the treatment of testicular ischemia and preventing its harmful impacts.

Keywords

Main Subjects

  1.  Yousefi-Manesh H, Shirooie S, Hemati S, Shokrian-Zeini M, Zarei N, Raoufi M, Farrokhi V, Dehpour A. Protective effects of modafinil administration on testicular torsion/detorsion damage in rats. Experimental and Molecular Pathology, 2019; 111: 104305.
  2. Arda E, Yuksel I, Akdere H, Akdeniz E, Yalta TD, Aktoz T, Altun GD. Contrary effects of coenzyme Q10 and vitamin E after testicular ischemia/reperfusion in a rat model validated with glucose metabolism imaging. Urologia, 2019; 88(1): 56-63.
  3. Mohamed NM, Kabil SL. Pioglitazone abrogates testicular damage induced by testicular torsion/detorsion in rats. Iranian Journal of Basic Medical Sciences, 2019, 22(8): 884.
  4. Ghasemnejad-Berenji M, Ghazi-Khansari M, Yazdani I, Saravi SSS, Nobakht M, Abdollahi A, Ansari JM, Ghasemnejad-Berenji H, Pashapour S, Dehpour AR. Rapamycin protects testes against germ cell apoptosis and oxidative stress induced by testicular ischemia-reperfusion. Iranian Journal of Basic Medical Sciences, 2017; 2 (8): 905.
  5.  Parlaktas BS, Atilgan D, Ozyurt H, Gencten Y, Akbas A, Erdemir F, Uluocak N. The biochemical effects of ischemia-reperfusion injury in the ipsilateral and contralateral testes of rats and the protective role of melatonin. Asian Journal of Andrology, 2014; 16(2): 314.
  6. Kanter M. Protective effects of melatonin on testicular torsion/detorsion-induced ischemia–reperfusion injury in rats. Experimental and Molecular Pathology, 2010, 89(3): 314-320.
  7. Taati M, Moghadasi M, Dezfoulian O, Asadian P, Zendehdel M. Effects of Ghrelin on germ cell apoptosis and proinflammatory cytokines production in Ischemia-reperfusion of the rat testis. Iranian Journal of Reproductive Medicine, 2015; 13(2): 85.
  8. Wang HW, Zhang Y, Tan PP, Jia LS, Chen Y, Zhou BH. Mitochondrial respiratory chain dysfunction mediated by ROS is a primary point of fluoride-induced damage in Hepa1-6 cells. Environmental Pollution, 2019; 255(Pt 3): 113359.
  9. Okamura K, Nakagama Y, Takeda N, Soma K, Sato T, Isagawa T, Kido Y, Sakamoto M, Manabe I, Hirata Y, Komuro I, Ono M. Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy. Journal of Pharmacological Sciences, 2019.
  10. Mirhadi E, Rezaee M, Malaekeh-Nikouei B. Nano strategies for berberine delivery a natural alkaloid of Berberis. Biomedicine & Pharmacotherapy, 2018; 104: 465-473.
  11. Ashrafizadeh M, Fekri H. S, Ahmadi Z, Farkhondeh T, Samarghandian S. Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway. Journal of Cellular Biochemistry, 2019.
  12. Mohammadinejad R, Ahmadi Z, Tavakol S, Ashrafizadeh M. Berberine as a potential autophagy modulator. Journal of Cellular Physiology, 2019.
  13. Mi J, He W, Lv J, Zhuang K, Huang H, Quan S. Effect of berberine on the HPA-axis pathway and skeletal muscle GLUT4 in type 2 diabetes mellitus rats. Diabetes Metabolic Syndrome and Obesity: Targets and Therapy, 2019; 12: 1717-1725.
  14. Zhang N, Sheng M, Wu M, Zhang X, Ding Y, Lin Y, Yu W, Wang S, Du H. Berberine protects steatotic donor undergoing liver transplantation via inhibiting endoplasmic reticulum stress-mediated reticulophagy. Experimental Biology and Medicine, 2019; 244(18): 1695-1704.
  15. Zeng Z, Pan Y, Wu W, Li L, Wu Z, Zhang Y, Deng B, Wei S, Zhang W, Lin F, Song Y. Myocardial hypertrophy is improved with berberine treatment via long non-coding RNA MIAT-mediated autophagy. The Journal of Pharmacy and Pharmacology, 2019; 71(12): 1822-1831.
  16. Singh AK, Singh SK, Nandi MK, Mishra G, Maurya A, Rai A, Rai GK, Awasthi R, Sharma B, Kulkarni GT. Berberine: A plant derived alkaloid with therapeutic potential to combat Alzheimer's disease. Central Nervous System Agents in Medicinal Chemistry, 2019; 19(3):154-170.
  17. Wang K, Chen Q, Wu N, Li Y, Zhang R, Wang J, Gong D, Zou X, Liu C, Chen J. Berberine ameliorates spatial learning memory impairment and modulates cholinergic anti-inflammatory pathway in diabetic rats. Frontiers in Pharmacology, 2019; 10: 1003.
  18. Zhao C, Su P, Lv C, Guo L, Cao G, Qin C, Zhang W. Berberine alleviates amyloid beta-induced mitochondrial dysfunction and synaptic loss. Oxidative Medicine and Cellular Longevity, 2019; 7593608.
  19. Hussien NR, Al-Kuraishy HM, Al-Gareeb AI. Reno-protective effect of berberine. JPMA. The Journal of the Pakistan Medical Association, 2019; 69 (8): S83-s87.
  20. Eftekhari A, Hasanzadeh A, Khalilov R, Hosainzadegan H, Ahmadian E, Eghbal MA. Hepatoprotective role of berberine against paraquat-induced liver toxicity in rat. Environmental Science and Pollution Research, 2020; 27(5): 4969-4975.
  21.  Li H, Fan C, Lu H, Feng C, He P, Yang X, Xiang C, Zuo J, Tang W. Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions. Acta Pharmaceutica Sinica B, 2020; 10(3): 447-461.
  22. Song J, Gao X, Tang Z, Li H, Ruan Y, Liu Z, Wang T, Wang S, Liu J, Jiang H. Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway. Andrology, 2020; 8(3): 793-806.
  23.  Jiang W, Li S, Chen X, Zhang W, Chang Y, He Y, Zhang S, Su X, Gao T, Li C, Jian Z. Berberine protects immortalized line of human melanocytes from H2O2-induced oxidative stress via activation of Nrf2 and Mitf signaling pathway. Journal of Dermatological Science, 2019; 94(1): 236-243.
  24.  Deng Y, Tang K, Chen R, Nie H, Liang S, Zhang J, Zhang Y, Yang Q. Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signaling pathway. Experimental and Therapeutic Medicine, 2019; 17(3): 2091-2098.
  25. Han CY, Sun TT, Xv GP, Wang SS, Gu JG, Liu CY. Berberine ameliorates CCl4‑induced liver injury in rats through regulation of the Nrf2‑Keap1‑ARE and p53 signaling pathways. Molecular Medicine Reports, 2019; 20(4): 3095-3102.
  26. Zhu X, Bian H, Wang L, Sun X, Xu X, Yan H, Xia M, Chang X, Lu Y, Li Y, Xia P, Li X, Gao X. Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free Radical Biology & Medicine, 2019; 141: 192-204.
  27. Hassani-Bafrani H, Najaran H, Razi M, Rashtbari H. Berberine ameliorates experimental varicocele-induced damages at testis and sperm levels; Evidences for oxidative stress and inflammation. Andrologia, 2019; 51(2): e13179.
  28. Liu DQ, Chen SP, Sun J, Wang XM, Chen N, Zhou YQ, Tian YK, Ye DW. Berberine protects against ischemia-reperfusion injury: A review of evidence from animal models and clinical studies. Pharmacological Research. 2019; 148: 104385.
  29. Zhu JR, Lu HD, Guo C, Fang WR, Zhao HD, Zhou JS, Wang F, Zhao YL, Li YM, Zhang YD, Yang CQ, Sun JG. Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation. Acta Pharmacologica Sinica, 2018; 39(11): 1706-1715.
  30. Zheng H, Lan J, Li J, Lv L. Therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2. Experimental and Therapeutic Medicine, 2018; 16(3): 2008-2012.
  31. Zhang Q, Bian H, Guo L, Zhu H. Berberine preconditioning protects neurons against ischemia via sphingosine-1-phosphate and hypoxia-inducible factor-1 α. The American Journal of Chinese Medicine, 2016; 44(05): 927-941.