Daneshvar Medicine

Daneshvar Medicine

Protective effect of ghrelin on histopathological alterations in renal tissue of mice treated with cyclophosphamide

Document Type : Original Article

Authors
Haniyeh AbdolahZadeh 1
Fatemeh Khoshdel 2
Fatemeh Ashory 3
Parviz Vahedi 4
Ramin Salimnejad 5
1 Students Research Committee, School of Paramedical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran.
2 Students Research Committee, School of Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran.
3 Department of Sports Physiology, Urmia University, Urmia, Iran.
4 Department of Anatomical Sciences, MaraghehUniversity of Medical Sciences Maragheh, Maragheh, Iran.
5 5. Department of Anatomical Sciences and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
10.22070/daneshmed.2021.13831.1035
Abstract
Background and Objective: Cyclophosphamide is one of the common medications in chemotherapy and suppression of the immune system in organ transplantation. The clinical use of cyclophosphamide has been reduced due to its many side effects due to reproductive, hepatic, renal, and cardiac toxicity in patients and animal models. This study aimed to evaluate the effect of ghrelin against cyclophosphamide-induced damage to renal tissue.
Materials and Methods: Thirty-two (2-month old) male mice were randomly divided into 4 groups: 1) control 2) cyclophosphamide 3) cyclophosphamide + ghrelin 4) ghrelin. Cyclophosphamide once a week (100 mg/kg) and ghrelin (80 μg/kg) were injected intraperitoneally daily for 5 weeks. After 5 weeks, the kidneys were removed and after weighing, tissue alterations were examined by hematoxylin-eosin and Periodic Acid Schiff staining.
Results: Findings showed that cyclophosphamide significantly reduces body weight and kidney weight and also significantly increases tissue damage (p < 0.05). Ghrelin treatment significantly improved the above parameters (p < 0.05).
Conclusion: The results of this study showed that ghrelin can reduce the destructive effects of cyclophosphamide in renal tissue.
Keywords
Cyclophosphamide
Ghrelin
Kidney
Mice
  1. Aladaileh SH, Al-Swailmi FK, Abukhalil MH, Shalayel MH. Renoprotective Effect of Formononetin against Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Kidney. Journal of Pharmaceutical Research International 2021; 33(2):26-37. doi: 10.9734/jpri/2021/v33i231144
  2. Lin X, Yang F, Huang J, Jiang S, Tang Y, Li J. Ameliorate effect of pyrroloquinoline quinone against cyclophosphamide-induced nephrotoxicity by activating the Nrf2 pathway and inhibiting the NLRP3 pathway. Life Sciences. 2020; 256:117901. doi: 10.1016/j.lfs.2020.117901.
  3. Samar O. Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma. Saudi Journal of Biological Science 2010; 17(2):105-14. doi: 10.1016/j.sjbs.2010.02.003.
  4. Lin X, Yang F, Huang J, Jiang S, Tang Y, Li J. Ameliorate effect of pyrroloquinoline quinone against cyclophosphamide-induced nephrotoxicity by activating the Nrf2 pathway and inhibiting the NLRP3 pathway. Life Sciences 2020; 256:117901. doi: 10.1016/j.lfs.2020.117901.
  5. Rehman MU, Tahir M, Ali F, Qamar W, Lateef A, Khan R, et al. Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid. Molecular and Cellular Biochemistry 2012; 365(1-2):119-27. doi: 10.1007/s11010-012-1250-x.
  6. Salimnejad R, Soleimani Rad J, Mohammad Nejad D, Roshangar L. Effect of ghrelin on total antioxidant capacity, lipid peroxidation, sperm parameters and fertility in mice against oxidative damage caused by cyclophosphamide. Andrologia 2018; 50(2). doi: 10.1111/and.12883.
  7. Venables G, Hunne B, Bron R, Cho H-J, Brock JA, Furness JB. Ghrelin receptors are expressed by distal tubules of the mouse kidney. Cell and Tissue Research 2011; 346(1):135-9. doi: 10.1007/s00441-011-1240-4.
  8. Fujimura K, Wakino S, Minakuchi H, Hasegawa K, Hosoya K, Komatsu M, et al. Ghrelin protects against renal damages induced by angiotensin-II via an antioxidative stress mechanism in mice. PLoS One 2014; 9(4):e94373. doi: 10.1371/journal.pone.0094373. eCollection 2014.
  9. Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, et al. Kidney produces a novel acylated peptide, ghrelin. FEBS letters 2000; 486(3):213-6. doi: 10.1016/s0014-5793(00)02308-5.
  10. Kacar AK, Sacan O, Ozicli N, Bolkent S, Yanardag R, Bolkent S. The Effects of Ghrelin on Renal Complications in Newborn Diabetic Rats. European Journal of Biology 2020;79(1):1-6. doi:10.26650/ EurJBiol.2020.0043.
  11. Wang W, Bansal S, Falk S, Ljubanovic D, Schrier R. Ghrelin protects mice against endotoxemia-induced acute kidney injury. American Journal of Physiology 2009; 297(4):F1032-7. doi: 10.1152/ajprenal.00044.2009.
  12. Zhang W, Shu L. Upregulation of miR-21 by ghrelin ameliorates ischemia/ reperfusion-induced acute kidney injury by inhibiting inflammation and cell apoptosis. DNA and cell Biology 2016; 35(8):417-25. doi: 10.1089/dna.2016.3231.
  13. Lu W-P, Mei X-T, Wang Y, Zheng Y-P, Xue Y-F, Xu D-H. Zn (II)–curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage. Environmental Toxicology and Pharmacology 2015; 39 (2) :515-24. doi: 10.1016/j.etap. 2014.12.014.
  14. Obay BD, Taşdemir E, Tümer C, Bilgin HM, Atmaca M. Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides 2008; 29(3):448-55. doi: 10.1016/j.peptides.2007.11.020
  15. Eyvazi M, Tayefi H, Abedelahi A, Salimnejad R, Majdi A. Effect of Vitamin E and Sodium Selenite on the Expression of Bax and Bcl2 Genes and Renal Histopathology in the Electromagnetic Field-Exposed Mice. Crescent Journal of Medical and Biological Sciences 2019; 6(4): 523–528.
  16. Mazani M, Rezagholizadeh L, Shamsi S, Mahdavifard S, Ojarudi M, Salimnejad R, et al. Protection of CCl4-induced hepatic and renal damage by linalool. Drug and Chemical Toxicology 2020: 1-9. doi: 10.1080/01480545.2020.1792487.
  17. Lopez SG, Luderer U. Effects of cyclophosphamide and buthionine sulfoximine on ovarian glutathione and apoptosis. Free Radical Biology and Medicine 2004; 36(11):1366-77. doi: 10.1016/j.freeradbiomed.2004.02.067.
  18. Aguilar-Mahecha A, Hales BF, Robaire B. Chronic cyclophosphamide treatment alters the expression of stress response genes in rat male germ cells. Biology of Reproduction 2002; 66(4):1024-32. doi: 10.1095/biolreprod66.4.1024.

 

  1. Gunes S, Sahinturk V, Uslu S, Ayhanci A, Kacar S, Uyar R. Protective effects of selenium on cyclophosphamide-induced oxidative stress and kidney injury. Biological Trace Element Research 2018; 185(1):116-123. doi: 10.1007/s12011-017-1231-8.
  2. Cuce G, Esen HH, Koc T, Canbaz HT, Limandal C, Kalkan S, et al. Vitamin E partially ameliorates cyclophosphamide-induced nephrotoxicity in rats. Progress in Nutrition 2016;18(2):140-145.
  3. Hazrati A, Salimnejad R, Alipour M, Mirzaei Bavil F, Alihemmati A. Protective effect of ghrelin on testicular damages caused by chronic hypoxia in rats: a histopathological study. Andrologia 2018;50(4):e12989. doi: 10.1111/and . 12989.
  4. Salama ME, Adel M, Helal G, El-Shafey M. Role of Oxidative Stress, Apoptosis and Autophagy in Cadmium-induced Renal Injury in Rats: Renoprotective Effect of Ghrelin. Bulletin of Egyptian Society for Physiological Sciences 2019;39(2):271-285. doi: 10.21608/BESPS. 2019. 14414. 1025
  5. Shati AA, El‐Kott AF. Acylated ghrelin protects against Doxorubicin‐induced nephropathy by activating SIRT1. Basic & Clinical Pharmacology & Toxicology 2021; 128(6):805-821. doi: 10.1111/bcpt.13569.
Daneshvar Medicine
Volume 29, Issue 2 - Serial Number 153
July and August 2021
Pages 1-11