A Histological Evaluation of the Effect of Ghrelin on Wound Healing in Rats

Abstract

Objective: This study aimed to investigate the potential effects of ghrelin on wound healing.

Materials and Methods: Sprague-Dawley rats were divided into 3 groups: Control (n = 8), wound-saline (W+S, n = 16), and wound-ghrelin (W+Gr, n = 16). A wound was created on the cervical back region of rats using an 8 mm biopsy punch tool in the W+S and W+Gr groups. Either saline (1 mL/kg) or ghrelin (10 ng/kg) was administrated intraperitoneally each day to the rats in the non-control groups after the onset of the wound. Rats from the W+S and W+Gr groups were euthanized on the 7th (n = 8 from each group) and 14th day (n = 8 from each group) of the experiment. The histopathological score was evaluated statistically using one-way analysis of variance and Tukey’s multiple comparison tests.

Results: The rats euthanized from the W+S group on day 7 (subgroup W+S7) showed degenerated epidermis, no hair follicles, presence of granulation tissue, inflammatory cell infiltration, vasocongestion, and increased collagen fibers in dermis. However, all these histopathological findings significantly decreased in the rats euthanized from the W+Gr group on day 7 (subgroup W+Gr7) compared to the W+S7 group (p < 0.05). The W+S14 group showed thick epidermis, a few hair follicles, angiogenesis, and increased collagen fibers in the dermis. Additionally, the histopathological findings decreased significantly in the W+Gr14 group compared to W+S14 group (p < 0.05).

Conclusion: Based on the statistical analysis of the histological findings, the ghrelin treatment appears to have a beneficial effect on wound healing.relin treatment might have a beneficial effect on wound healing.

Keywords

• Wound healing
• Ghrelin
• Histology

References

1. 1. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008; 453(7193): 314-21. [CrossRef] google scholar
2. 2. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54(12): e132-73. [CrossRef] google scholar
3. 3. Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: Role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery. Adv Skin Wound Care 2012; 25(8): 349-70. [CrossRef] google scholar
4. 4. Tschop M., Smiley D.L., Heiman M.L. Ghrelin induces adiposity in rodents. Nature 2000; 407(6806): 908-13. [CrossRef] google scholar
5. 5. Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, et al. Ghrelin. Mol Metab 2015; 4(6): 437-60. [CrossRef] google scholar
6. 6. Shah KG, Wu R, Jacob A, Blau SA, Ji Y, Dong W, et al. Human ghrelin ameliorates organ injury and improves survival after radiation injury combined with severe sepsis. Mol Med 2009; 15(11-12): 407-14. [CrossRef] google scholar
7. 7. Liu C, Huang J, Li H, Yang Z, Zeng Y, Liu J, et al. Ghrelin accelerates wound healing through GHS-Rla-mediated MAPK-NF-kB/GR signaling pathways in combined radiation and burn injury in rats. Sci Rep 2016; 6: 27499. [CrossRef] google scholar
8. 8. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US); 2011. google scholar

9. 9. Işeri SO, Sener G, Yüksel M, Contuk G, Cetinel S, Gedik N, et al. Ghrelin against alendronate-induced gastric damage in rats. J Endocrinol 2005; 187(3): 399-406. [CrossRef] google scholar
10. 10. Sidhu GS, Thaloor D, Singh AK, Raghunath PN, Maheshwari RK. Enhanced biosynthesis of extracellular matrix proteins and TGF-ß1 by polyinosinic-polycytidylic acid during cutaneous wound healing in vivo. J Cell Physiol 1996; 169(1): 108-14. [CrossRef] google scholar
11. 11. Aktop, S, Çaliskan Ak E, Emekli-Alturfan E, Gocmen G, Atali O, Ercan F, et al. Effects of ankaferd blood stopper on soft tissue healing in warfarin-treated rats. Int J Med. Res Health Sci 2016; 5(5): 200-9. google scholar
12. 12. Zarchi K, Martinussen T, Jemec GB. Wound healing and all-cause mortality in 958 wound patients treated in-home care. Wound Repair Regen 2015; 23(5): 753-8. [CrossRef] google scholar
13. 13. Sen CK. Human Wounds and Its Burden: An Updated Compendium of Estimates. Adv Wound Care (New Rochelle) 2019; 8(2): 39-48. [CrossRef] google scholar
14. 14. Rousselle P, Braye F, Dayan G. Re-epithelialization of adult skin wounds: Cellular mechanisms and therapeutic strategies. Adv Drug Deliv Rev 2019; 146: 344-65. [CrossRef] google scholar
15. 15. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from the stomach. Nature 1999; 402(6762): 656-60. [CrossRef] google scholar
16. 16. Ersahin M, Toklu HZ, Erzik C, Cetinel S, Akakin D, Velioğlu-Oğünç A, et al. The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats. J Neurotrauma 2010; 27(6): 1143-55. [CrossRef] google scholar
17. 17. Warzecha Z, Ceranowicz D, Dembinski A, Ceranowicz P, Cieszkowski J, Kuwahara A, et al. Ghrelin accelerates the healing of cysteamine-induced duodenal ulcers in rats. Med Sci Monit 2012; 18(5): BR181-7. [CrossRef] google scholar
18. 18. Ceranowicz P, Warzecha Z, Dembinski A, Sendur R, Cieszkowski J, Pawlik WW, et al. Treatment with ghrelin accelerates the healing of acetic acid-induced gastric and duodenal ulcers in rats. J Physiol Pharmacol 2009; 60(1): 87-98. google scholar
19. 19. Sehirli O, Sener E, Sener G, Cetinel S, Erzik C, Yeğen BC. Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides 2008; 29(7): 1231-40. [CrossRef] google scholar
20. 20. Cieszkowski J, Warzecha Z, Ceranowicz P, Ceranowicz D, Kusnierz-Cabala B, Pedziwiatr M, et al. Therapeutic effect of exogenous ghrelin in the healing of gingival ulcers is mediated by the release of endogenous growth hormone and insulin-like growth factor-1. J Physiol Pharmacol 2017; 68(4): 609-17. google scholar
21. 21. Lyra Junior HF, de Lucca Schiavon L, Rodrigues IK, Couto Vieira DS, de Paula Martins R, Turnes BL, et al. Effects of ghrelin on the oxidative stress and healing of the colonic anastomosis in rats. J Surg Res 2019; 234: 167-77. [CrossRef] google scholar
22. 22. Liu C, Hao Y, Huang J, Li H, Yang Z, Zeng Y, et al. Ghrelin accelerates wound healing in combined radiation and wound injury in mice. Exp Dermatol 2017; 26(2): 186-93. [CrossRef] google scholar