Original Article

Iodine induces toxicity against Candida albicans and Candida glabrata through oxidative stress


Background and Objectives: Candida species are antifungal-resistant opportunistic infections that spread through contaminated medical staff hands and hospital surfaces creating a nosocomial infection risk. Iodine´s antibacterial properties are well established; however, its antifungal properties remain unknown. The objective of this study was to investigate the antifungal effects of lugol on cell viability and oxidative stress on Candida albicans and Candida glabrata strains.
Materials and Methods: MTT reduction test and sensitivity growth assay were used to determine viability and minimal inhibitory concentration, colorimetric tests were used to analyzing lipoperoxidation and antioxidant status in C. albicans, parental C. glabrata, C. glabrata lacking catalase gene (cta1) and superoxide dismutase 1 and 2 double mutants (sod1sod2∆) strains exposure to lugol were used.
Results: In both C. albicans and C. glabrata wild types lugol treatment decreased cellular viability in a dose-dependent manner at 30 mm. The cytotoxic lugol effect was characterized by the increase of oxidative stress and the reduction of superoxide dismutase and catalase enzyme activities. C. glabrata strains lacking catalase (cta1) and superoxide dismutase 1 and 2 double mutants (sod1sod2∆) were less resistant to lugol than parental C. glabrata strains.
Conclusion: In Candida strains iodine lugol solution has antifungal properties, producing cytotoxicity and oxidative stress. Superoxide dismutase 1 and 2 activities are involved in resistance of Candida to iodine.

1. Mehta Y, Gupta A, Todi S, Myatra S, Samaddar DP, Patil V, et al. Guidelines for prevention of hospital acquired infections. Indian J Crit Care Med 2014; 18:149-163.
2. Rencber S, Karavana SY, Yilmaz FF, Erac B, Nenni M, Ozbal S, et al. Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis. Int J Nanomedicine 2016; 11:2641-2653.
3. Roques C, Al Mousa H, Duse A, Gallagher R, Koburger T, Lingaas E, et al. Consensus statement: patient safety, healthcare-associated infections and hospital environmental surfaces. Future Microbiol 2015; 10:1629-1634.
4. García-Cruz CP, Najera AMJ, Arroyo-Helguera OE. Fungal and bacterial contamination on indoor surfaces of a hospital in Mexico. Jundishapur J Microbiol 2012; 5:460-464.
5. World Health Organization Prevention of hospital-acquired infections: A practical guide. (2002) https://apps.who.int/iris/bitstream/handle/10665/67350/WHO_CDS_CSR_EPH_2002.12.pdf
6. Durnas B, Wnorowska U, Pogoda K, Deptula P, Watek M, Piktel E, et al. Candidacidal activity of selected ceragenins and human cathelicidin ll-37 in experimental settings mimicking infection sites. PLoS One 2016; 11(6):e0157242.
7. Arendrup MC. Candida and candidaemia. susceptibility and epidemiology. Dan Med J 2013; 60:B4698.
8. Stojanovic P, Stojanovic N, Stojanovic-Radic Z, Arsic Arsenijevic V, Otasevic S, Randjelovic P, et al. Surveillance and characterization of Candida bloodstream infections in a Serbian tertiary care hospital. J Infect Dev Ctries 2016; 10:643-656.
9. Pathirana RU, Friedman J, Norris HL, Salvatori O, McCall AD, Kay J, et al. Fluconazole-Resistant Candida auris is susceptible to salivary histatin 5 killing and to intrinsic host defenses. Antimicrob Agents Chemother 2018; 62(2):e01872-17.
10. Zhang L, Xiao M, Watts MR, Wang H, Fan X, Kong F, et al. Development of fluconazole resistance in a series of Candida parapsilosis isolates from a persistent candidemia patient with prolonged antifungal therapy. BMC Infect Dis 2015; 15:340.
11. Briones-Martin-Del-Campo M, Orta-Zavalza E, Canas-Villamar I, Gutierrez-Escobedo G, Juarez-Cepeda J, Robledo-Marquez K, et al. The superoxide dismutases of Candida glabrata protect against oxidative damage and are required for lysine biosynthesis, DNA integrity and chronological life survival. Microbiology (Reading) 2015; 161:300-310.
12. Cuellar-Cruz M, Briones-Martin-del-Campo M, Canas-Villamar I, Montalvo-Arredondo J, Riego-Ruiz L, Castano I, et al. High resistance to oxidative stress in the fungal pathogen Candida glabrata is mediated by a single catalase, Cta1p, and is controlled by the transcription factors Yap1p, Skn7p, Msn2p, and Msn4p. Eukaryot Cell 2008; 7:814-825.
13. Roetzer A, Klopf E, Gratz N, Marcet-Houben M, Hiller E, Rupp S, et al. Regulation of Candida glabrata oxidative stress resistance is adapted to host environment. FEBS Lett 2011; 585:319-327.
14. Buettner GR. Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide. Anticancer Agents Med Chem 2011;11:341-346.
15. Briones-Martin-Del-Campo M, Orta-Zavalza E, Juarez-Cepeda J, Gutierrez-Escobedo G, Canas-Villamar I, Castano I, et al. The oxidative stress response of the opportunistic fungal pathogen Candida glabrata. Rev Iberoam Micol 2014; 31:67-71.
16. Cuellar-Cruz M, Castano I, Arroyo-Helguera O, De Las Penas A. Oxidative stress response to menadione and cumene hydroperoxide in the opportunistic fungal pathogen Candida glabrata. Mem Inst Oswaldo Cruz 2009; 104:649-654.
17. Han JH, Sullivan N, Leas BF, Pegues DA, Kaczmarek JL, Umscheid CA. Cleaning hospital room surfaces to prevent health care–associated infections: a technical brief. Ann Intern Med 2015; 163:598-607.
18. Tortola GJ, Funke BR, Case CL (2007). Introducción a la microbiología. 9nd ed. Médica Panamericana. Buenos aires, Argentina
19. Vidal ZE, Rufino SC, Tlaxcalteco EH, Trejo CH, Campos RM, Meza MN, et al. Oxidative stress increased in pregnant women with iodine deficiency. Biol Trace Elem Res 2014; 157:211-217.
20. Tonoyan L, Boyd A, Fleming GTA, Friel R, Gately CM, Mc Cay PH, et al. In vitro comparative cytotoxicity study of a novel biocidal iodo-thiocyanate complex. Toxicol In Vitro 2018;50:264-273.
21. Hussein Ael-A, Abbas AM, El Wakil GA, Elsamanoudy AZ, El Aziz AA. Effect of chronic excess iodine intake on thyroid function and oxidative stress in hypothyroid rats. Can J Physiol Pharmacol 2012; 90:617-625.
22. Hombach M, Maurer FP, Pfiffner T, Böttger EC, Furrer R. Standardization of operator-dependent variables affecting precision and accuracy of the disk diffusion method for antibiotic susceptibility testing. J Clin Microbiol 2015;53:3864-3869.
23. Castano I, Pan SJ, Zupancic M, Hennequin C, Dujon B, Cormack BP. Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol Microbiol 2005; 55:1246-1258.
24. De Las Penas A, Pan SJ, Castano I, Alder J, Cregg R, Cormack BP. Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. Genes Dev 2003; 17:2245-2258.
25. Campanha NH, Pavarina AC, Brunetti IL, Vergani CE, Machado AL, Spolidorio DM. Candida albicans inactivation and cell membrane integrity damage by microwave irradiation. Mycoses 2007;50:140-147.
26. McCord JM. Analysis of superoxide dismutase activity. Curr Protoc Toxicol 2001; Chapter 7:Unit 7.3.
27. Linares CE, Giacomelli SR, Altenhofen D, Alves SH, Morsch VM, Schetinger MR. Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis. Rev Soc Bras Med Trop 2013;46:752-758.
28. Hoekstra MJ, Westgate SJ, Mueller S. Povidone-iodine ointment demonstrates in vitro efficacy against biofilm formation. Int Wound J 2017; 14:172-179.
29. Selvaggi G, Monstrey S, Van Landuyt K, Hamdi M, Blondeel P. The role of iodine in antisepsis and wound management: a reappraisal. Acta Chir Belg 2003; 103:241-247.
30. Bigliardi PL, Alsagoff SAL, El-Kafrawi HY, Pyon JK, Wa CTC, Villa MA. Povidone iodine in wound healing: A review of current concepts and practices. Int J Surg 2017; 44:260-268.
31. Kaneda Y, Tsutsumi Y, Yoshioka Y, Kamada H, Yamamoto Y, Kodaira H, et al. The use of PVP as a polymeric carrier to improve the plasma half-life of drugs. Biomaterials 2004;25:3259-3266.
32. Oesch F, Honarvar N, Fabian E, Berger FI, Landsiedel R. N-vinyl compounds: studies on metabolism, genotoxicity, carcinogenicity. Arch Toxicol 2021;95:3143-3159.
33. Oesch F, Fruth D, Hengstler JG, Fabian E, Berger FI, Landsiedel R. Enigmatic mechanism of the N-vinylpyrrolidone hepatocarcinogenicity in the rat. Arch Toxicol 2021;95:3717-3744.
34. Küpper FC, Carrano CJ. Key aspects of the iodine metabolism in brown algae: a brief critical review. Metallomics 2019;11:756-764.
35. Arroyo-Helguera O, Anguiano B, Delgado G, Aceves C. Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line. Endocr Relat Cancer 2006; 13:1147-1158.
36. Arroyo-Helguera O, Rojas E, Delgado G, Aceves C. Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects. Endocr Relat Cancer 2008; 15:1003-1011.
37. Joanta AE, Filip A, Clichici S, Andrei S, Daicoviciu D. Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones. Acta Physiol Hung 2006; 93:347-359.
38. Kitagawa E, Akama K, Iwahashi H. Effects of iodine on global gene expression in Saccharomyces cerevisiae. Biosci Biotechnol Biochem 2005; 69:2285-2293.
39. Heseltine P (2001). Disinfection, Sterilization, and Preservation. In: Infection control & hospital epidemiology. Ed, SS Block.. Lippincott Williams & Wilkins, 5th Ed. Philadelphia, pp. 109-109.
40. Yao X, Li M, He J, Zhang G, Wang M, Ma J, et al. Effect of early acute high concentrations of iodide exposure on mitochondrial superoxide production in FRTL cells. Free Radic Biol Med 2012; 52:1343-1352.
IssueVol 14 No 2 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v14i2.9195
Iodine; Oxidative stress; Antioxidants; Candida; Antifungal agents

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How to Cite
Cuellar-Rufino S, Arroyo-Xochihua O, Salazar-Luna A, Arroyo-Helguera O. Iodine induces toxicity against Candida albicans and Candida glabrata through oxidative stress. Iran J Microbiol. 2022;14(2):260-267.