“From Bedside to Bench and Back Again”: Análise Exploratória do Papel dos Óleos Essenciais como Potencial Tratamento da Queratite Fúngica
DOI:
https://doi.org/10.48560/rspo.38196Palavras-chave:
Antifúngicos, Óleos Voláteis, Queratite/tratamentoResumo
INTRODUÇÃO: O objetivo deste estudo foi avaliar a eficácia antifúngica de óleos essenciais (OE) extraídos de plantas medicinais: Lavandula pedunculata (Mill.) Cav. (nativa do Vale do Côa, Portugal) e Cymbopogon citratus (DC.) Stapf, contra agentes da queratite fúngica (QF).MÉTODOS: Foram colhidas amostras de córnea de doentes com suspeita de queratite infeciosa na ULS Coimbra (Coimbra) e na ULS São João (Porto). Os isolamentos fúngicos confirmados foram caracterizados. Foi avaliada a sua suscetibilidade aos OEs em diversas concentrações, pelo método de disco-difusão em fase sólida, determinando as suas propriedades inibitórias e fungicidas. Os diâmetros da zona de inibição (IZD) em redor dos discos foram registados aos 3º, 5º, 7º, 10º e 14º dias de incubação.
RESULTADOS: Catorze amostras positivas foram obtidas em 6 meses. Observou-se um predomínio de Candida spp. O OE de Cymbopogon citratus demonstrou uma atividade antifúngica excecional, com inibição completa de Aspergillus fumigatus e Scedosporium apiospermum em todas as concentrações, mantendo IZDs máximos durante os 14 dias. Contra Candida spp., o IZD para Cymbopogon citratus aumentou ao longo do tempo, à concentração de 100%, tendo evoluído de 68 mm (ao 3º dia) para 81,7 mm (ao 14º dia), no caso de Candida albicans, e de 51,7 mm para 71,3 mm, no caso de Candida parapsilosis. O OE de Lavandula pedunculata apresentou elevada atividade contra Aspergillus fumigatus e Scedosporium apiospermum, no início da incubação, diminuindo os IZDs ao longo do tempo, independente da concentração do OE. A sua eficácia contra Candida spp. mostrou baixa atividade, sendo variável ao longo do tempo e da concentração.
CONCLUSÃO: Os OEs de Cymbopogon citratus e Lavandula pedunculata constituem alternativos agentes antifúngicos, fornecendo bases para o desenvolvimento de novos tratamentos. A eficácia notável de OE de Cymbopogon citratus contra vários agentes favorece a sua utilização na prática clínica, enquanto o OE de Lavandula pedunculata requer mais estudos esclarecedores do seu potencial antifúngico. Otimizar as concentrações de OE e a duração da exposição é crucial para maximizar a sua eficácia. São necessários mais estudos para compreender o papel dos OEs no microambiente corneano e o seu contributo para o desenvolvimento de novos fármacos.
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Referências
Acharya Y, Acharya B, Karki P. Fungal keratitis: study of increasing trend and common determinants. Nepal J Epidemiol. 2017;7:685–93.
Xie L, Zhong W, Shi W, Sun S. Spectrum of fungal keratitis in north China. Ophthalmology. 2006;113:1943–1948.
Gopinathan U, Ramakrishna T, Willcox M, Rao CM, Balasubramanian D, Kulkarni A, et al. Enzymatic, clinical and histologic evaluation of corneal tissues in experimental fungal keratitis in rabbits. Exp Eye Res. 2001;72:433–42.
Ferrer C, Alió JL. Evaluation of molecular diagnosis in fungal keratitis. Ten years of experience. J Ophthalmic Inflamm Infect. 2011;1:15–22.
Awad R, Ghaith AA, Awad K, Mamdouh Saad M, Elmassry AA. Fungal keratitis: Diagnosis, management, and recent advances. Clin Ophthalmol. 2024;18:85–106. doi: 10.2147/OPTH.S447138.
Deshmukh R, Stevenson L, Vajpayee R. Management of corneal perforations: An update. Indian J Ophthalmol. 2020;68:7. doi: 10.4103/ijo.IJO_1151_19.
Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils--a review. Food Chem Toxicol. 2008;46:446–75.
Ramsey JT, Shropshire BC, Nagy TR, Chambers KD, Li Y, Korach KS. Essential oils and health. Yale J Biol Med. 2020;93:291–305.
Kajjari S, Joshi RS, Hugar SM, Gokhale N, Meharwade P, Uppin C. The effects of lavender essential oil and its clinical implications in dentistry: a review. Int J Clin Pediatr Dent. 2022;15:385–8. doi: 10.5005/jp-journals-10005-2378.
Homa M, Fekete IP, Böszörményi A, Singh YRB, Selvam KP, Shobana CS, et al. Antifungal effect of essential oils against Fusarium keratitis isolates. Planta Med. 2015;81:1277–1284.
Tyagi AK, Malik A. Antimicrobial potential and chemical composition of Eucalyptus globulus oil in liquid and vapour phase against food spoilage microorganisms. Food Chem. 2011;126:228–235.
Kumar P, Mishra S, Kumar A, Sharma AK. Antifungal efficacy of plant essential oils against stored grain fungi of Fusarium spp. J Food Sci Technol. 2016;53:3725–3734.
Zuzarte M, Salgueiro L. Essential oils in respiratory mycosis: A review. Molecules. 2022;27:4140. doi: 10.3390/molecules27134140.
Pattnaik S, Subramanyam VR, Kole C. Antibacterial and antifungal activity of ten essential oils in vitro. Microbios. 1996;86:237–46.
Marouf RS, Mbarga JAM, Ermolaev AV, Podoprigora IV, Smirnova IP, Yashina NV, et al. Antibacterial Activity of Medicinal Plants against Uropathogenic Escherichia coli. J Pharm Bioallied Sci. 2022;14:1–12. doi: 10.4103/jpbs.jpbs_124_21.
Cavanagh HMA, Wilkinson JM. Biological activities of lavender essential oil. Phytother Res. 2002;16:301–308.
Cox-Georgian D, Ramadoss N, Dona C, Basu C. Therapeutic and medicinal uses of terpenes. Medicinal Plants. 2019;333–359.
BLAST: Basic Local Alignment Search Tool. Bethesda: National Center Biotechnology Information; 2024.
Fungal descriptions and antifungal susceptibility. In: Mycology | University of Adelaide [Internet]. [cited 29 Sep 2024]. Available: https://www.adelaide.edu.au/mycology/fungal-descriptions-and-antifungal-susceptibility.
Clsi. Performance standards for antifungal susceptibility testing of yeasts. CLSI supplement M60. 2017.
Rex JH. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: approved standard. (No Title). 2008. [cited 29 Sep 2024] Available: https://cir.nii.ac.jp/crid/1130000793857084928.
Shah G, Shri R, Panchal V, Sharma N, Singh B, Mann AS. Scientific basis for the therapeutic use of Cymbopogon citratus, stapf (Lemon grass). J Adv Pharm Technol Res. 2011;2:3–8.
Ahmadikia K, Aghaei Gharehbolagh S, Fallah B, Naeimi Eshkaleti M, Malekifar P, Rahsepar S, et al. Distribution, prevalence, and causative agents of fungal keratitis: A systematic review and meta-analysis (1990 to 2020). Front Cell Infect Microbiol. 2021;11:698780. doi: 10.3389/fcimb.2021.698780.
Soleimani M, Izadi A, Khodavaisy S, Dos Santos CO, Tehupeiory-Kooreman MC, Ghazvini RD, et al. Fungal keratitis in Iran: Risk factors, clinical features, and mycological profile. Front Cell Infect Microbiol. 2023;13:1094182. doi: 10.3389/fcimb.2023.1094182.
El-Badry AS, Ali SS. Essential Oils: A Promising Remedy against Fungal and Bacterial Human Keratitis. 2015;II:403–431.
Yu B, Li C, Gu L, Zhang L, Wang Q, Zhang Y, et al. Eugenol protects against Aspergillus fumigatus keratitis by inhibiting inflammatory response and reducing fungal load. Eur J Pharmacol. 2022;924:174955. doi: 10.1016/j.ejphar.2022.174955.
Radhakrishnan N, Pathak N, Subramanian KR, Das DR, Ningombam R, Khaitan I, et al. Comparative study on costs incurred for treatment of patients with bacterial and fungal keratitis - A retrospective analysis. Indian J Ophthalmol. 2022;70:1191–5. doi: 10.4103/ijo.IJO_2176_21.
Ashfaq H, Maganti N, Ballouz D, Feng Y, Woodward MA. Procedures, visits, and procedure costs in the management of microbial keratitis. Cornea. 2021;40:472–6. doi: 10.1097/ICO.0000000000002534.
Chantra S, Jittreprasert S, Chotcomwongse P, Amornpetchsathaporn A. Estimated direct and indirect health care costs of severe infectious keratitis by cultured organisms in Thailand: An 8-year retrospective study. PLoS One. 2023;18:e0288442. doi: 10.1371/journal.pone.0288442.
Thomas CM, Shae W, Koestler D, DeFor T, Bahr NC, Alpern JD. Antifungal drug price increases in the United States, 2000-2019. Mycoses. 2022;65:859–65. doi: 10.1111/myc.13486.
Vilas-Boas AA, Goméz-García R, Machado M, Nunes C, Ribeiro S, Nunes J, et al. Lavandula pedunculata polyphenol-rich extracts obtained by conventional, MAE and UAE methods: Exploring the bioactive potential and safety for use as a medicine plant, food, and nutraceutical ingredient. Foods. 2023;12:4462.
Alara OR, Abdurahman NH, Ukaegbu CI. Extraction of phenolic compounds: A review. Curr Res Food Sci. 2021;4:200–214.
Castiello C, Junghanns P, Mergel A, Jacob C, Ducho C, Valente S, et al. GreenMedChem: The challenge in the next decade toward eco-friendly compounds and processes in drug design. Green Chem. 2023;25:2109–69.
Ghenciu LA, Faur AC, Bolintineanu SL, Salavat MC, Maghiari AL. Recent advances in diagnosis and treatment approaches in fungal keratitis: A narrative review. Microorganisms. 2024;12. doi: 10.3390/microorganisms12010161.
Martin MJ, Rahman MR, Johnson GJ, Srinivasan M, Clayton YM. Mycotic keratitis: susceptibility to antiseptic agents. Int Ophthalmol. 1995;19:299–302.
Hoffman JJ, Yadav R, Sanyam SD, Chaudhary P, Roshan A, Singh SK, et al. Topical chlorhexidine 0.2% versus topical natamycin 5% for the treatment of fungal keratitis in Nepal: A randomized controlled noninferiority trial. Ophthalmology. 2022;129:530–41. doi: 10.1016/j.ophtha.2021.12.004.
Hoffman JJ, Yadav R, Das Sanyam S, Chaudhary P, Roshan A, Singh SK, et al. Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomized controlled non-inferiority trial. BMJ Open. 2020;10:e038066. doi: 10.1136/bmjopen-2020-038066.
Hoffman JJ, Arunga S, Mohamed Ahmed AHA, Hu VH, Burton MJ. Management of filamentous fungal keratitis: A pragmatic approach. J Fungi. 2022;8:1067.
Ramatchandirane B, Chandrika YM, Najeeb S. Successful management of fungal keratitis caused by multidrug-resistant Cladosporium species using povidone-iodine. Cornea. 2024;43:125–8. doi: 10.1097/ICO.0000000000003390.
Sushma MV, Sankaranarayanan SA, Bantal V, Pemmaraju DB, Rengan AK. Ethosomal nanoformulations for combinational photothermal therapy of fungal keratitis. Adv Ther. 2023;2200331.
Nakarani M, Misra AK, Patel JK, Vaghani SS. Itraconazole nanosuspension for oral delivery: Formulation, characterization and in vitro comparison with marketed formulation. Daru. 2010;18:84–90.
Huang J-F, Zhong J, Chen G-P, Lin Z-T, Deng Y, Liu Y-L, et al. A hydrogel-based hybrid theranostic contact lens for fungal keratitis. ACS Nano. 2016;10:6464–73.
Ciolino JB, Hudson SP, Mobbs AN, Hoare TR, Iwata NG, Fink GR, et al. A prototype antifungal contact lens. Invest Ophthalmol Vis Sci. 2011;52:6286–91.
Hung JH, Lee CN, Hsu HW, Ng I-S, Wu CJ, Yu CK, et al. Recent advances in photodynamic therapy against fungal keratitis. Pharmaceutics. 2021;13:2011. doi: 10.3390/pharmaceutics13122011.
González Castellanos JC, Osaba M, Reviglio V, Canchi MT, Arrigone MC, Reviglio VE. Early treatment of bilateral fungal keratitis with corneal cross-linking as adjuvant therapy. Oxf Med Case Rep. 2020;2020:omaa032.
Mikropoulos DG, Kymionis GD, Voulgari N, Kaisari E, Nikolakopoulos KA, Katsanos A, et al. Intraoperative photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) during penetrating keratoplasty for the management of fungal keratitis in an immunocompromised patient. Ophthalmol Ther. 2019;8:491–5. doi: 10.1007/s40123-019-0196-4.
Jeyalatha Mani V, Parthasarathy D, Padmanabhan P, Narayanan N, Lakshmipathy M, Pachayappan SK, et al. Therapeutic effect of corneal crosslinking on fungal keratitis: Efficacy of corneal collagen crosslinking as an adjuvant therapy for fungal keratitis in a tertiary eye hospital in south India. Ocul Immunol Inflamm. 2021;29:1648–55.
Prajna NV, Radhakrishnan N, Lalitha P, Austin A, Ray KJ, Keenan JD, et al. Cross-linking-assisted infection reduction: A randomized clinical trial evaluating the effect of adjuvant cross-linking on outcomes in fungal keratitis. Ophthalmology. 2020;127:159–66. doi: 10.1016/j.ophtha.2019.08.029.
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Direitos de Autor (c) 2025 Revista Sociedade Portuguesa de Oftalmologia
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