Effects of dose-dependent chronic caffeine consumption in a rat burn wound model: Histopathological and immunohistochemical evaluation

Document Type : Original Article

Authors

1 Hitit University, Training and Research Hospital, IVF Center, Corum, Turkey

2 Dokuz Eylul University, Faculty of Medicine, Department of Histology and Embryology, Izmir, Turkey

3 Hitit University, Training and Research Hospital, Pathology Department, Corum, Turkey

4 Dokuz Eylul University, Faculty of Medicine, Department of Obstetrics and Gynecology, Izmir, Turkey

Abstract

Objective(s): Using histopathological and immunohistochemical methods, we aimed to examine the dose-dependent effects of chronic caffeine consumption on the recovery of burn wounds in an in vivo rat model.
Materials and Methods: Forty-five rats were randomly assigned to a high-dose group (20 mg/kg per day for eight weeks; n=15), a low-dose group (10 mg/kg per day for eight weeks; n=15), or a control group (n=15). The burn model was created in rats. The groups were separated into three subgroups (n=5) based on the day after injury (7th, 14th, or 21st day). The wound area, wound closure percentage, and histopathological and immunohistochemical reactivity were evaluated.
Results: Successful wound healing was noted in rats treated with low doses of caffeine, similar to the control group. Pathology revealed low re-epithelization, low inflammation, and high granulation in the high-dose group. In addition, there was a significant difference between the control and high-dose groups regarding the immunohistochemical reactivity of αVβ3 integrin, VEGF, and MMP-9 (P<0.05).
Conclusion: We demonstrated that chronic caffeine consumption in rats adversely affects the recovery process of wounds in a dose-dependent manner. This effect may occur through delayed wound healing via the molecules MMP-9, αVβ3 integrin, and VEGF. Treatment that modulates these molecules can lead to enhanced and quicker recovery of damaged skin in coffee lovers.

Keywords

Main Subjects

References

1. Quain AM, Khardori NM. Nutrition in wound care management: A Comprehensive Overview. Wounds 2015;27:327-335. 
2. Shirakata Y, Kimura R, Nanba D, Iwamoto R, Tokumaru S, Morimoto C, et al. Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing. J Cell Sci 2005;118:2363-2370.
3. DiPietro LA. Angiogenesis and wound repair: When enough is enough. J Leukoc Biol 2016; 100: 979-984. 
4. Yan X, Chen B, Lin Y, Li Y, Xiao Z, Hou X, et al. Acceleration of diabetic wound healing by collagen-binding vascular endothelial growth factor in diabetic rat model. Diabetes Res Clin Pract 2010; 90: 66-72.
5. Loyd CM, Diaconu D, Fu W, Adams GN, Brandt E, Knutsen DA, et al. Transgenic overexpression of keratinocyte-specific VEGF and Ang1 in combination promotes wound healing under nondiabetic but not diabetic conditions. Int J Clin Exp Pathol 2012; 5: 1-11. 
6. Rohani MG, Parks WC. Matrix remodeling by MMPs during wound repair. Matrix Biol 2015; 44-46: 113-121. 
7. Doersch KM, Newell-Rogers MK. The impact of quercetin on wound healing relates to changes in αV and β1 integrin expression. Exp Biol Med 2017; 242: 1424-1431.
8. Duperret EK, Natale CA, Monteleon C, Dahal A, Ridky TW. The integrin αv-TGFβ signaling axis is necessary for epidermal proliferation during cutaneous wound healing. Cell Cycle 2016; 15: 2077-2086.
9. Hu X, Li N, Tao K, Fang X, Liu J, Wang Y, et al. Effects of integrin ανβ3 on differentiation and collagen synthesis induced by connective tissue growth factor in human hypertrophic scar fibroblasts. Int J Mol Med 2014; 34: 1323-1334.
10. Ojeh N, Stojadinovic O, Pastar I, Sawaya A, Yin N, Tomic‐Canic M. The effects of caffeine on wound healing. Int Wound J 2016; 13: 605-613.
11. Han W, Ming M, He YY. Caffeine promotes ultraviolet B-induced apoptosis in human keratinocytes without complete DNA repair. J Biol Chem 2011; 286: 22825-22832.
12. Li H, Jin SY, Son HJ, Seo JH, Jeong GB. Caffeine-induced endothelial cell death and the inhibition of angiogenesis. Anat Cell Biol 2013; 46: 57-67.
13. Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR. Topical application of Aloe vera accelerated wound healing, modeling, and remodeling: An experimental study. Ann Plast Surg 2016; 77: 37-46. 
14. White RD, Holdaway BB, Moody JD, Chang, Y. Chronic caffeine administration attenuates vascular injury-induced neointimal hyperplasia in rats. J Caffeine Res 2013; 3: 163-168.
15. Duarte PM, Marques MR, Bezerra JP, Bastos, MF. The effects of caffeine administration on the early stage of bone healing and bone density: A histometric study in rats. Arch Oral Biol 2009; 54: 717-722.
16. Nasiri E, Hosseinimehr SJ, Azadbakht M, Akbari J, Enayati-Fard R, Azizi S. Effect of Malva sylvestris cream on burn injury and wounds in rats. Avicenna J Phytomed 2015; 5: 341-354.
17. Mehrabani D, Farjam M, Geramizadeh B, Tanideh N, Amini M, Panjehshahin MR. The healing effect of curcumin on burn wounds in rat. World J Plast Surg 2015; 4: 29-35.
18. Amiri ZM, Tanideh N, Seddighi A, Mokhtari M, Amini M, Partovi AS, et al. The effect of lithospermum officinale, silver sulfadiazine and alpha ointments in healing of burn wound injuries in rat. World J Plast Surg 2017; 6: 313-318.
19. Simonetti O, Lucarini G, Cirioni O, Zizzi A, Orlando F, Provinciali M, et al. Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression. Burns 2013; 39: 776-787. 
20. Oryan A, Alemzadeh E, Mohammadi AA. Application of honey as a protective material in maintaining the viability of adipose stem cells in burn wound healing: A histological, molecular and biochemical study. Tissue Cell 2019; 61: 89-97.
21. Sagliyan A, Ceribasi A, Gunay C, Han M, Benzer F,  Kandemir M. Effects of dietary supplementation with whey proteins on surgical wound healing in rats. Rev Med Vet 2010; 161: 455-462. 
22. Sarsmaz K, Goker A, Micili SC, Ergur BU, Kuscu NK. Immunohistochemical and ultrastructural analysis of the effect of omega-3 on embryonic implantation in an experimental mouse model. Taiwanese J Obstet Gynecol 2016; 55: 351-356. 
23. Rahman MS, Islam R, Rana MM, Spitzhorn LS, Rahman MS, Adjaye J, et al. Characterization of burn wound healing gel prepared from human amniotic membrane and Aloe vera extract. BMC Complement Altern Med 2019; 19: 1-15. 
24. Hosny EN, Sawie HG, Elhadidy ME, Khadrawy YA. Evaluation of antioxidant and anti-inflammatory efficacy of caffeine in rat model of neurotoxicity. Nutr Neurosci 2019; 22: 789-796.
25. Amer MG, Mazen NF, Mohamed AM. Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: A biochemical and histological study. Int J Immunopathol Pharmacol 2017; 30: 13-24.
26. Hwang JH, Kim KJ, Ryu SJ, Lee BY. Caffeine prevents LPS-induced inflammatory responses in RAW264. 7 cells and zebrafish. Chem Biol Interact 2016; 248: 1-7.
27. Wadhwa M, Chauhan G, Roy K, Sahu S, Deep S, Jain V, et al. Caffeine and modafinil ameliorate the neuroinflammation and anxious behavior in rats during sleep deprivation by inhibiting the microglia activation. Front Cell Neurosci 2018;12: 49-64. 
28. Nessler M, Puchala J, Wood FM, Wallace HJ, Fear MW, Nessler K, et al. Changes in the plasma cytokine and growth factor profile are associated with impaired healing in pediatric patients treated with INTEGRA® for reconstructive procedures. Burns 2013; 39: 667-673.
29. Ching YH, Sutton TL, Pierpont YN, Robson MC, Payne WG. The use of growth factors and other humoral agents to accelerate and enhance burn wound healing. Eplasty 2011: 11: e41-61.
30. Maugeri G, D’Amico AG, Rasà DM, Saccone S, Federico C, Magro G, et al. Caffeine effect on HIFs/VEGF pathway in human glioblastoma cells exposed to hypoxia. Anticancer Agents  Med Chem 2018; 18: 1432-1439.
31. Liu J, Zhu G, Jia N, Wang W, Wang Y, Yin M, et al. CD9 regulates keratinocyte migration by negatively modulating the sheddase activity of ADAM17. Int J Biol Sci 2019; 15: 493-506. 
32. Okonkwo UA, Chen L, Ma D, Haywood VA, Barakat M, Urao N, et al. Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. PloS One 2020; 15: e0231962-231978. 
33. Kenny FN, Connelly JT. Integrin-mediated adhesion and mechano-sensing in cutaneous wound healing. Cell Tissue Res 2015; 360: 571-582.
34. El Kahi CG, Atiyeh BS, Abdallah Hajj Hussein I, Jurjus R, Dibo SA, Jurjus A, et al. Modulation of wound contracture α‐smooth muscle actin and multispecific vitronectin receptor integrin αvβ3 in the rabbit’s experimental model. Int Wound J 2009; 6: 214-224.
35. Dasu MR, Spies M, Barrow RE, Herndon DN. Matrix metalloproteinases and their tissue inhibitors in severely burned children. Wound Repair Regen 2003; 11: 177-180.
36. Nagy B, Szélig L, Rendeki S, Loibl C, Rézmán B, Lantos J, et al. Dynamic changes of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 after burn injury. J Crit Care 2015; 30: 162-166.
37. Yilmaz F, Tekmen I. The dosage-dependent prenatal caffeine exposure adversely affects levels of integrin αVβ3 and MMP-9 in a rat model of embryo implantation. Bratisl Lek Listy 2020; 121: 648-655.
38. Cheng YC, Ding YM, Hueng DY, Chen JY, Chen Y. Caffeine suppresses the progression of human glioblastoma via cathepsin B and MAPK signaling pathway. J Nutr Biochem 2016; 33: 63-72.
39. Liu WH, Chang LS. Caffeine induces matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 down‐regulation in human leukemia U937 cells via Ca2+/ROS‐mediated suppression of ERK/c‐fos pathway and activation of p38 MAPK/c‐jun pathway. J Cell Physiol 2010; 224: 775-785. 
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 9
September 2024
Pages 1180-1186

Files

Share

How to cite

Statistics