Nephroprotective and anti-inflammatory effects of resveratrol topical ointment in albino rats following full-thickness cutaneous burn wound
Background: Recent studies on resveratrol (RSV) have generated great interest, owing to its pleiotropic, health-promoting properties that have been documented not only in animals but also in humans to exhibit anti-neoplastic and alleviate oxidative stress and inflammation, anti-diabetic, protective role in cardiac diseases, and anti-ulcerative properties, among others.
Aims: This study is aimed at evaluating the effects of topical RSV ointment on hematology, serum biochemistry, and serum vascular endothelial growth factor (VEGF), following full-thickness cutaneous burn wound (BW).
Methods: Four groups of 15 rats were arranged in groups A (negative control), B (positive drug control; BW + 1% silver sulphadiazine [SSD] cream), C (experimental group; BW + 5% RSV topical application), and D (positive wound control; BW with no topical application of ointment). The dorsum was shaved using a clipper, and 23.5 mm of BW was inflicted in groups B–D. Rats from groups B and C were treated twice daily for 21 days. Five rats from each group were anesthetized on days 5, 8, and 21, and blood samples were collected post-wounding (PW).
Results: A statistically significant reduction in neutrophil and monocyte counts in the RSV-treated group was recorded (P < 0.05). Increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities on day 5 were due to acute hepatic injury associated with burns but were normalized on days 8 and 21. Serum levels of urea and creatinine were lower in the RSV-treated group than in the SSD-treated group on days 5 and 8 post-treatment (PT). The RSV-treated group had a lower VEGF concentration in comparison to other groups.
Conclusion: The study demonstrated that RSV suppresses neutrophil and monocyte counts in the peripheral circulation, thus acting as an anti-inflammatory compound. Similarly, RSV exhibited a nephroprotective effect by suppressing creatinine and urea levels. RSV reportedly suppressed the serum activity of VEGF, making it a good antineoplastic agent.
Relevance for Patients: RSV formulation can be used to enhance BW healing in human patients through its anti-inflammatory effect. RSV can also ameliorate kidney dysfunction associated with BW in human patients.
[1] Kameshwaran S, Senthilkumar R, Thenmozhi S, Dhanalakshmi M. Wound Healing Potential of Ethanolic Extract of Tecoma Stans Flowers in Rats. Pharmacologia 2014;5:215-21. doi: 10.5567/pharmacologia.2014.215.221
[2] Garcia-Espinoza JA, Aguilar-Aragon VB, OrtizVillalobos EH, Garcia-Manzano RA, Antonio BA. Burns: Definition, Classification, Pathophysiology and Initial Approach. Gen Med (Los Angeles) 2017;5:298. doi: 10.4172/2327-5146.1000298
[3] Shah A, Amini-Nik S. The Role of Phytochemicals in the Inflammatory Phase of Wound Healing. Int J Mol Sci 2017;18:1068. doi: 10.3390/ijms18051068
[4] Velnar T, Bailey T, Smrkolj V. The Wound Healing Process: An Overview of the Cellular and Molecular mechanisms. J Int Med Res 2009;37:1528-42. doi: 10.1177/147323000903700531
[5] Jasiński M, Jasińska L, Ogrodowczyk M. Resveratrol in Prostate Diseases - A Short Review. Cent European J Urol 2013;66:144-9. doi: 10.5173/ceju.2013.02.art8
[6] Afshar M, Hassanzadeh-Taheri MM, Zardast M, Moghaddam A. The Angiogenetic Effect of Resveratrol on Dermal Wound Healing in Balb/C Mice. Mod Care J 2017;14:e66118. doi: 10.5812/modernc.66118
[7] Brâkenhielm E, Cao, R, Cao R. Suppression of Angiogenesis, Tumor Growth, and Wound Healing by Resveratrol, A Natural Compound in Red Wine and Grapes. FASEB J 2001;15:1798-800. doi: 10.1096/fj.01-0028fje
[8] Miguel NA, Andrade SF, Nai G, Laposy CB, Nascimento FF, Dinallo HR, et al. Effects of Resveratrol on Liver Function of Obese Female Wistar Rats. Cienc Anim Bras 2016;17:402-10. doi: 10.1590/1089-6891v17i332990
[9] Atmaca N, Yildirim E, Güner B, Kabakçi R, Bilmen FS. Effect of Resveratrol on Hematological and Biochemical Alterations in Rats Exposed to Fluoride. BioMed Res Int 2014;2014:698628. doi: 10.1155/2014/698628
[10] Sterling JP, Heimbach DM, Gibran NS. Manangement of Burn Wound. In: ACS Surgery, Principles and Practice: Trauma and Thermal Injury. Hamilton, ON: Decker; 2010. p. 1-13.
[11] Hosseinimehr SJ, Khorasani G, Azadbakht M, Zamani P, Ghasemi M, Ahmadi A. Effect of Aloe Cream Versus Silver Sulfadiazine for Healing Burn Wounds in Rats. Acta Dermatovenerol Croat 2010;18:2-7.
[12] Karunanidhi A, Ghaznavi-Rad E, Jeevajothi Nathan J, Abba Y, van Belkum A, Neela V. Allium stipitatum Extract Exhibits in vivo Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus and Accelerates Burn Wound Healing in a Full-thickness Murine Burn Model. Evid Based Complement Alternat Med 2017;2017:1914732. doi: 10.1155/2017/1914732.
[13] Cai EZ, Ang CH, Raju A, Tan KB, Hing EC, Loo Y, et al. Creation of Consistent Burn Wounds: A Rat Model. Arch Plast Surg 2014;41:317-24. doi: 10.5999/aps.2014.41.4.317
[14] Guo HF, Ali RM, Hamid RA, Zaini AA, Khaza’ai H. A New Model for Studying Deep Partial-Thickness Burns in Rats. Int J Burns Trauma 2017;7:107-14.
[15] Thrall MA, Weiser G, Allison RW, Campbell TW. Veterinary Hematology and Clinical Chemistry. 2nd ed. United States: John Wiley and Sons, Inc.; 2012. p. 17-43.
[16] Reitmans S, Frankel SA. A Colorimetric Method for the Determination of Serum Glutamic Oxalacetic and Glutamic Pyruvic Transaminase. Am J Clin Pathol 1957;28:56-63. doi: 10.1093/ajcp/28.1.56
[17] Juan ME, Vinardell P, Planas JM. The Daily Oral Administration of High Doses of Trans-Resveratrol to Rats for 28 Days is Not Harmful. J Nutr 2002;132:257-60. doi: 10.1093/jn/132.2.257
[18] Donnely LE, Newton R, Kennedy GE, Fenwick PS, Leung RH, Ito K, et al. Anti-inflammatory Effects of Resveratrol in Lung Epithelial Cells: Molecular Mechanisms. Am J Physiol Lung Cell Mol Physiol 2004;287:774-83. doi: 10.1152/ajplung.00110.2004
[19] Moon SO, Kim W, Sung MJ, Lee S, Kang KP, Kim DH, et al. Resveratrol Suppresses Tumor Necrosis FactorAlpha-Induced Fractalkine Expression in Endothelial Cells. Mol Pharmacol 2006;70:112-9. doi: 10.1124/mol.106.022392
[20] Hişmioğullari SE, Hişmioğullari AA, Yavuz MT, Yavuz, Ö, Yaman İ, Seyrek K, et al. The Protective Effect of Resveratrol in Experimentally Induced Non-Sterile Clean Wound Inflammation in Rats. Kafkas Univ Vet Fak Derg 2013;19:A1-5. doi: 10.9775/kvfd.2012.6989
[21] Jeschke MG. The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes? Mol Med 2009;15:337-51. doi: 10.2119/molmed.2009.00005
[22] Yoksa DT, Abba Y, Shamaki BU, Satumari NA. Effects of Resveratrol Topical Ointment on Wound Healing of Full-Thickness Cutaneous Burns in Albino Rats. J Wound Care 2022;31:780-91. doi: 10.12968/jowc.2022.31.9.780
[23] Jeschke MG, Micak RP, Finnerty CC, Herndon DN. Changes in Liver Function and Size after a Severe Thermal Injury. Shock 2007;28:172-7.doi: 10.1097/shk.0b013e318047b9e2
[24] Nielson CB, Duethman NC, Howard JM, Moncure M, Wood JG. Burns: Pathophysiology of Systemic Complications and Current Management. J Burn Care Res 2017;38:e469-81. doi: 10.1097/BCR.0000000000000355
[25] Dolezelova E, Prasnicka A, Cermanova J, Carazo A, Hyrsova L, Hroch M, et al. Resveratrol Modifies Biliary Secretion of Cholephilic Compounds in ShamOperated and Cholestatic Rats. World J Gastroenterol 2017;23:7678-92. doi: 10.3748/wjg.v23.i43.7678
[26] Hong AH, Bae SY, Ahn SY, Kim J, Kwon YJ, Jung WY, et al. Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of SIRT1-PGC1α-Foxo1 Signaling in Mice. Kidney Blood Press Res 2017;42:641-53. doi: 10.1159/000481804
[27] Grujić-Milanović J, Jaćević V, Miloradović Z, Milanović SD, Jovović D, Ivanov M, et al. Resveratrol Improved Kidney Function and Structure in Malignantly Hypertensive Rats by Restoration of Antioxidant Capacity and Nitric Oxide Bioavailability. Biomed Pharmacother 2022;154:113642. doi: 10.1016/j.biopha.2022.113642
[28] Maroz N, Simman R. Wound Healing in Patients with Impaired Kidney Function. J Am Coll Clin Wound Spec 2013;5:2-7. doi: 10.1016/j.jccw.2014.05.002
[29] Hu WH, Duan R, Xia YT, Xiong QP, Wang HY, Chan GK, et al. Binding of Resveratrol to Vascular Endothelial Growth Factor Suppresses Angiogenesis by Inhibiting the Receptor Signaling. JAgric Food Chem 2019;67:1127-37. doi: 10.1021/acs.jafc.8b05977
[30] Lee CS, Choi EY, Lee SC, Koh HJ, Lee JH, Chung HC. Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization. Yonsei Med J 2015;56:1678-85. doi: 10.3349/ymj.2015.56.6.1678
[31] Kasowanjete P, Dhilip Kumar SS, Houreld NN. AReview of Photobiomodulation on PI3K/AKT/mTOR in Wound Healing. J Photochem Photobiol 2024;19:100215. doi: 10.1016/j.jpap.2023.100215
[32] Gan D, Su Q, Su H, Wu L, Chen J, Han B, et al. Burn Ointment Promotes Cutaneous Wound Healing by Modulating the PI3K/AKT/mTOR Signaling Pathway. Front Pharmacol. 2021;12:631102. doi: 10.3389/fphar.2021.631102
[33] Bejenaru LE, Biţă A, Belu I, Segneanu AE, Radu A, Dumitru A, et al. Resveratrol: AReview on the Biological Activity and Applications. Appl Sci 2024;14:4534. doi: 10.3390/app14114534