EXPERIMENTAL RESEARCH
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Burn wound healing is a complex, dynamic process that involves a coordinated cascade of cellular responses and phases. Inflammation, proliferation and remodeling are the main phases of tissue repair, while tumor necrosis factor α (TNF-α) and procalcitonin (PCT) seem to be important mediators affecting the inflammatory state. Our aim was to assess the effect of rosuvastatin on tissue repair after partial thickness burn injury in healthy animals.

Material and methods:
In this randomized prospective experimental study, 36 male rats were randomly divided into two groups: placebo-treated (PG) and topical rosuvastatin-treated (SG). Under anesthesia, a partial-thickness burn trauma was induced in the dorsal region of the rats using an iron seal. Tissue samples were collected for histopathological examination as well.

Results:
Variables of TNF-α, procalcitonin and macroscopic assessment were normally distributed between the two groups on all studied days. The expression of TNF-α was found to be lower in burn injuries treated with topical rosuvastatin in comparison with placebo-treated animals on days 3, 6 and 9. PCT values in rosuvastatin-treated subgroups were statistically significantly lower than in placebo subgroups. Upon macroscopic examination, a significantly smaller burnt area in the statin-treated group was detected compared to the non-statin group on all days, except for day 3. Histopathological examination demonstrated higher levels of mean neutrophil infiltration in the placebo group (day 3). Finally, fibroblast proliferation, angiogenesis and re-epithelization levels were noted to be higher after the topical application of rosuvastatin.

Conclusions:
Rosuvastatin accelerated wound healing and down-regulated TNF-α and PCT levels.
REFERENCES (70)
1.
Tomic-Canic M, Burgess JL, O’Neill KE, Strbo N, Pastar I. Skin microbiota and its interplay with wound healing. Am J Clin Dermatol 2020; 21 (Suppl 1): 36-43.
 
2.
Trejos M, Aristizabal Y, Aragón-Muriel A, Oñate-Garzón J, Liscano Y. Characterization and classification in silico of peptides with dual activity (antimicrobial and wound healing). Int J Mol Sci 2023; 24: 13091.
 
3.
Walter AS, Volkmer E, Gauglitz G, Böcker W, Saller MM. Systematic review of molecular pathways in burn wound healing. Burns 2023; 49: 1525-33.
 
4.
Wu J, Zhang F, Liu J, Yao H, Wang Y. Effect of silver-containing hydrofiber dressing on burn wound healing: a meta-analysis and systematic review. J Cosmet Dermatol 2023; 22: 1685-91.
 
5.
Deana NF, Zaror C, del Sol M, Bagnato VS, Alves N. Wound contraction rate in excised and unexcised burn wounds with laser photobiomodulation: systematic review and meta-analysis of preclinical studies. Burns 2023; 49: 261-74.
 
6.
Fijany AJ, Givechian KB, Zago I, et al. Tranexamic acid in burn surgery: a systematic review and meta-analysis. Burns 2023; 49: 1249-59.
 
7.
Sharda D, Ghosh S, Kaur P, Basu B, Choudhury D. Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing. Discover Nano 2023; 18: 154.
 
8.
Dong Y, Wang Z. ROS-scavenging materials for skin wound healing: advancements and applications. Front Bioeng Biotechnol 2023; 11: 1304835.
 
9.
Irilouzadian R, Khalaji A, Baghsheikhi H, et al. The clinical outcomes of xenografts in the treatment of burn patients: a systematic review and meta-analysis. Eur J Med Res 2023; 28: 524.
 
10.
Qiao Y, Zhang Q, Peng Y, et al. Effect of stem cell treatment on burn wounds: a systemic review and a meta-analysis. Int Wound J 2023; 20: 8-17.
 
11.
Maita KC, Avila FR, Torres-Guzman RA, et al. Local anti-inflammatory effect and immunomodulatory activity of chitosan-based dressing in skin wound healing: a systematic review. J Clin Transl Res 2022; 8: 488-98.
 
12.
Qian H, Shan Y, Gong R, et al. Fibroblasts in scar formation: biology and clinical translation. Oxid Med Cell Longev 2022; 2022: 4586569.
 
13.
Qiao Z, Yang H, Jin L, Li S, Wang X. The efficacy and safety of botulinum toxin injections in preventing postoperative scars and improving scar quality: a systematic review and meta-analysis. Aesthetic Plast Surg 2021; 45: 2350-62.
 
14.
Correa-Araujo L, Prieto-Abello L, Lara-Bertrand A, et al. Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair. Stem Cell Res Ther 2023; 14: 306.
 
15.
Jaam M, Al-Naimi HN, Haddad MM, Abushanab D, Al-Badriyeh D. Comparative efficacy and safety among high-intensity statins. Systematic review and meta-analysis. J Comp Eff Res 2023; 12: e220163.
 
16.
Pertzov B, Eliakim-Raz N, Atamna H, Trestioreanu AZ, Yahav D, Leibovici L. Hydroxymethylglutaryl-CoA reductase inhibitors (statins) for the treatment of sepsis in adults – a systematic review and meta-analysis. Clin Microbiol Infect 2019; 25: 280-9.
 
17.
Lehtisalo M, Taskinen S, Tarkiainen EK, et al. A comprehensive pharmacogenomic study indicates roles for.
 
18.
SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics. Br J Clin Pharmacol 2023; 89: 242-52.
 
19.
Salem HF, Nafady MM, Ewees MGED, Hassan H, Khallaf RA. Rosuvastatin calcium-based novel nanocubic vesicles capped with silver nanoparticles-loaded hydrogel for wound healing management: optimization employing Box–Behnken design: in vitro and in vivo assessment. J Liposome Res 2022; 32: 45-61.
 
20.
Friedrich EE, Sun LT, Natesan S, Zamora DO, Christy RJ, Washburn NR. Effects of hyaluronic acid conjugation on anti-TNF- inhibition of inflammation in burns. J Biomed Mater Res A 2014; 102: 1527-36.
 
21.
Hassan J, Khan S, Zahra R, et al. Role of procalcitonin and c-reactive protein as predictors of sepsis and in managing sepsis in postoperative patients: a systematic review. Cureus 2022; 14: e31067.
 
22.
Huang YH, Chen CJ, Shao SC, et al. Comparison of the diagnostic accuracies of monocyte distribution width, procalcitonin, and C-reactive protein for sepsis: a systematic review and meta-analysis. Crit Care Med 2023; 51: e106-14.
 
23.
Molano-Franco D, Arevalo-Rodriguez I, Muriel A, et al. Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis. Diagn Progn Res 2023; 7: 15.
 
24.
Yaseen HS, Asif M, Saadullah M, et al. Methanolic extract of Ephedra ciliata promotes wound healing and arrests inflammatory cascade in vivo through downregulation of TNF-. Inflammopharmacology 2020; 28: 1691-704.
 
25.
Verras GI, Mulita F. Butyrylcholinesterase levels correlate with surgical site infection risk and severity after colorectal surgery: a prospective single-center study. Front Surg 2024; 11: 1379410.
 
26.
Zhu S, Zeng C, Zou Y, Hu Y, Tang C, Liu C. The clinical diagnostic values of SAA, PCT, CRP, and IL-6 in children with bacterial, viral, or co-infections. Int J Gen Med 2021; 14: 7107-13.
 
27.
De Filippo O, D’Ascenzo F, Iannaccone M, et al. Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials. Cardiovasc Diabetol 2023; 22: 324.
 
28.
Stefanou MI, Palaiodimou L, Katsanos AH, et al. The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord 2022; 58: 103395.
 
29.
Jamialahmadi T, Abbasifard M, Reiner Ž, Rizzo M, Eid AH, Sahebkar A. The effects of statin treatment on serum ferritin levels: a systematic review and meta-analysis. J Clin Med 2022; 11: 5251.
 
30.
Di Spirito F, Schiavo L, Pilone V, Lanza A, Sbordone L, D’Ambrosio F. Periodontal and peri-implant diseases and systemically administered statins: a systematic review. Dent J (Basel) 2021; 9: 100.
 
31.
Acton EK, Khazaal O, Willis AW, et al. Statins for the prevention of post-stroke seizure and epilepsy development: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis 2021; 30: 106024.
 
32.
Vahedian-Azimi A, Heidari Beni F, Fras Z, et al. Effects of statins on the incidence and outcomes of acute kidney injury in critically ill patients: a systematic review and meta-analysis. Arch Med Scie 2023; 19: 952-64.
 
33.
Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 2017; 58: 81-94.
 
34.
Liberale L, Carbone F, Camici GG, Montecucco F. IL-1 and statin treatment in patients with myocardial infarction and diabetic cardiomyopathy. J Clin Med 2019; 8: 1764.
 
35.
Chen YR, Xiang XD, Sun F, et al. Simvastatin reduces NETosis to attenuate severe asthma by inhibiting PAD4 expression. Oxid Med Cell Longev 2023; 2023: 1493684.
 
36.
Beales ILP, Ogunwobi OO. Leptin activates Akt in oesophageal cancer cells via multiple atorvastatin-sensitive small GTPases. Mol Cell Biochem 2021; 476: 2307-16.
 
37.
González-Herrera F, Clayton NS, Guzmán-Rivera D, et al. Statins change the cytokine profile in Trypanosoma cruzi-infected U937 macrophages and murine cardiac tissue through Rho-associated kinases inhibition. Front Immunol 2023; 13: 1035589.
 
38.
Bedi O, Dhawan V, Sharma PL, Kumar P. Pleiotropic effects of statins: new therapeutic targets in drug design. Naunyn Schmiedebergs Arch Pharmacol 2016; 389: 695-712.
 
39.
Ramhormozi P, Ansari JM, Simorgh S, et al. Simvastatin accelerates the healing process of burn wound in Wistar rats through Akt/mTOR signaling pathway. Ann Anatomy 2021; 236: 151652.
 
40.
Ansari JM, Ramhormozi P, Shabani R, et al. Simvastatin combined with bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis through SDF-1/CXCR4 pathway. Iran J Basic Med Sci 2020; 23: 751-9.
 
41.
Hosny KM, Alhakamy NA, Sindi AM, Khallaf RA. Coconut oil nanoemulsion loaded with a statin hypolipidemic drug for management of burns: formulation and in vivo evaluation. Pharmaceutics 2020; 12: 11-6.
 
42.
Zhao G, Yu YM, Kaneki M, Tompkins RG, Fischman AJ. Simvastatin protects hepatocytes from apoptosis by suppressing the TNF-/caspase-3 signaling pathway in mice with burn injury. Ann Surg 2013; 257: 1129-36.
 
43.
Boyko T, Marin C, Furnari G, Flynn W, Lukan JK. Safety profile of atorvastatin in the role of burn wound injury conversion. Am J Surg 2020; 220: 1323-6.
 
44.
Akershoek JJ, Brouwer KM, Vlig M, et al. Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds. PLoS One 2017; 12: e0179350.
 
45.
Suzuki-Banhesse VF, Azevedo FF, Araujo EP, et al. Effect of atorvastatin on wound healing in rats. Biol Res Nurs 2015; 17: 159-68.
 
46.
Laing T, Hanson R, Chan F, Bouchier-Hayes D. Effect of pravastatin on experimental diabetic wound healing.
 
47.
J Surg Res 2010; 161: 336-40.
 
48.
Sukpat S, Israsena N, Patumraj S. Pleiotropic effects of simvastatin on wound healing in diabetic mice. J Med Assoc Thai 2016; 99: 213-9.
 
49.
Abdelfattah U, Elbanoby T, Kim EN, Park EJ, Suh HP, Hong JPJ. Effect of simvastatin use in free tissue transfer: an experimental study in a rat epigastric free flap model. J Reconstr Microsurg 2020; 36: 281-8.
 
50.
Wang L, Luan Y, Jia C, et al. Pharmacokinetic interactions and tolerability of rosuvastatin and ezetimibe: a randomized, phase 1, crossover study in healthy Chinese participants. Eur J Drug Metab Pharmacokinet 2023; 48: 51-62.
 
51.
Vrzal R, Zenata O, Bachleda P, Dvorak Z. The effects of drugs with immunosuppressive or immunomodulatory activities on xenobiotics-metabolizing enzymes expression in primary human hepatocytes. Toxicol Vitro 2015; 29: 1088-99.
 
52.
Climent E, Benaiges D, Pedro-Botet J. Hydrophilic or lipophilic statins? Front Cardiovasc Med 2021; 8: 687585.
 
53.
Bener A, Dogan M, Barakat L, Al-Hamaq AOAA. Comparison of cost-effectiveness, safety, and efficacy of rosuvastatin versus atorvastatin, pravastatin, and simvastatin in dyslipidemic diabetic patients with or without metabolic syndrome. J Prim Care Community Health 2014; 5: 180-7.
 
54.
Sivkov A, Chernus N, Gorenkov R, Sivkov S, Sivkova S, Savina T. Relationship between genetic polymorphism of drug transporters and the efficacy of Rosuvastatin, atorvastatin and simvastatin in patients with hyperlipidemia. Lipids Health Dis 2021; 20: 157.
 
55.
Kavalipati N, Shah J, Ramakrishan A, Vasnawala H. Pleiotropic effects of statins. Indian J Endocrinol Metab 2015; 19: 554.
 
56.
Qiu Y, Wu Y, Meng M, et al. Rosuvastatin improves myocardial and neurological outcomes after asphyxial cardiac arrest and cardiopulmonary resuscitation in rats. Biomed Pharmacother 2017; 87: 503-8.
 
57.
Husain I, Khan S, Khan S, Madaan T, Kumar S, Najmi AK. Unfolding the pleiotropic facades of rosuvastatin in therapeutic intervention of myriads of neurodegenerative disorders. Clin Exp Pharmacol Physiol 2019; 46: 283-91.
 
58.
Li YH, Wang QX, Zhou JW, et al. Effects of rosuvastatin on expression of angiotensin-converting enzyme 2 after vascular balloon injury in rats. J Geriatr Cardiol 2013; 10: 151-8.
 
59.
Bifulco M, Gazzerro P. Statins in coronavirus outbreak: it’s time for experimental and clinical studies. Pharmacol Res 2020; 156: 104803.
 
60.
Boczar KE, Faller E, Zeng W, et al. Anti-inflammatory effect of rosuvastatin in patients with HIV infection: an FDG-PET pilot study. J Nucl Cardiol 2022; 29: 3057-68.
 
61.
Hearps AC, Angelovich TA, Trevillyan JM, et al. Effect of rosuvastatin therapy on biomarkers of inflammation and immune activation in people with human immunodeficiency virus at intermediate cardiovascular risk. J Infect Dis 2021; 224: 667-72.
 
62.
Santovito D, Marcantonio P, Mastroiacovo D, et al. High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion. Int J Cardiol 2020; 299: 249-53.
 
63.
Kummen M, Solberg OG, Storm-Larsen C, et al. Rosuvastatin alters the genetic composition of the human gut microbiome. Sci Rep 2020; 10: 5397.
 
64.
Tanaka S, Fukumoto Y, Nochioka K, et al. Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation. Arterioscler Thromb Vasc Biol 2013; 33: 1591-600.
 
65.
Thangamani S, Mohammad H, Abushahba MFN, et al. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. Sci Rep 2015; 5: 16407.
 
66.
Pradeep AR, Karvekar S, Nagpal K, Patnaik K, Raju A, Singh P. Rosuvastatin 1.2 mg in situ gel combined with 1:1 mixture of autologous platelet-rich fibrin and porous hydroxyapatite bone graft in surgical treatment of mandibular class II furcation defects: a randomized clinical control Trial. J Periodontol 2016; 87: 5-13.
 
67.
Balakumar K, Raghavan CV, Selvan NT, Prasad RH, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf B Biointerfaces 2013; 112: 337-43.
 
68.
Abdullahi A, Amini-Nik S, Jeschke MG. Animal models in burn research. Cell Mol Life Sci 2014; 71: 3241-55.
 
69.
Munteanu A, Florescu IP, Nitescu C. A modern method of treatment: the role of silver dressings in promoting healing and preventing pathological scarring in patients with burn wounds. J Med Life 2016; 9: 306-15.
 
70.
Synodinou D, Savoie-White FH, Sangone A, et al. Health utilities in burn injury survivors: a systematic review. Burns 2022; 48: 13-22.
 
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