Photodynamic Therapy Using Toluidine Blue O (TBO) Dye as a Photosensitizer against Leishmania major
-
Mehdi Najm
,
Maryam Pourhajibagher
,
Alireza Badirzadeh
,
Elham Razmjou
,
Maryam Alipour
,
Majid Khoshmirsafa
,
Abbas Bahador
,
Ramtin Hadighi
Abstract
Background: Photodynamic therapy (PDT) is alternative treatment of cutaneous leishmaniasis (CL), and phenolthiazine dyes such as Toluidine Blue O (TBO) have the potential role in PDT and notably affect parasites inactivation. This study aimed to evaluate the effectiveness of PDT by using TBO and a light-emitting diode (LED) in the treatment of zoonotic CL (ZCL).
Methods: The study was conducted in Iran University of Medical Sciences, Tehran, Iran in 2018-2020. Different concentration (7.8 µg/ mL up to 500 µg/ mL) of TBO as a photosensitizer and a 630 nm LED light as a source of light were used for antileishmanial activity against both forms of Leishmania major promastigotes and intracellular amastigotes. Effective concentration (EC50) and cell cytotoxicity (CC50) were calculated in both infected and non-infected J774.A1 macrophages, respectively. As well as inhibitory concentration (IC50) was quantified in L. major promastigotes for 2 h, 24 h, and 48 h after incubation using a MTT colorimetric assay.
Results: TBO dye in combination with the PDT significantly decreases the L. major promastigotes and intracellular amastigotes viability when compared with TBO alone. Both TBO dye in combination with the PDT and TBO alone had no toxic effects on the mice macrophages; however, it significantly killed the entered parasites inside the cells. Our results in the current study established satisfactory findings in clearing intracellular L. major parasites in in-vitro conditions.
Conclusion: TBO dye in combination with the PDT can be considered as a harmless, effective and importantly perfect treatment against L. major, causative agent of ZCL, in an in-vitro situation without any negative toxicity to the mice macrophages.
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4. Croft SL, Coombs GH (2003). Leishmaniasis–current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol, 19(11): 502-8.
5. Ouellette M, Drummelsmith J, Papadopoulou B (2004). Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist Updat, 7(4-5): 257-66.
6. Heidari‐Kharaji M., Fallah‐Omrani V, Badirzadeh A, et al (2019). Sambucus ebulus extract stimulates cellular responses in cutaneous leishmaniasis. Parasite Immunol, 41(1): e12605.
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8. Kazemi-Rad E, Mohebali M, Khadem-Erfan MB, et al (2013). Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach. Exp Parasitol, 135(2): 344-49.
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10. Taylor VM, Cedeño DL, Munoz DL, et al (2011). In vitro and in vivo studies of the utility of dimethyl and diethyl carbaporphyrin ketals in treatment of cutaneous leishmaniasis. Antimicrob Agents Chemother, 55(10): 4755-64.
11. Barbosa AF, Sangiorgi BB, Galdino SL, Barral‐Netto M, Pitta IR, Pinheiro AL (2012). Photodynamic antimicrobial chemotherapy (PACT) using phenothiazine derivatives as photosensitizers against Leishmania braziliensis. Lasers Surg Med, 44(10): 850-55.
12. Pizinger K, Cetkovska P, Kacerovska D, Kumpova M (2009). Successful treatment of cutaneous leishmaniasis by photodynamic therapy and cryotherapy. Eur J Dermatol, 19(2): 172-3.
13. Dai T, Huang Y-Y, Hamblin MR (2009). Photodynamic therapy for localized infections—state of the art. Photodiagnosis Photodyn Ther, 6(3-4): 170-88.
14. Oleinick NL, Evans HH (1998). The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat Res, 150(5 Suppl): S146-56.
15. Simpson ER, Wilson BC, Corriveau C, Murphy J (1987). Thermal damage and haematoporphyrin-derivative-sensitized photochemical damage in laser irradiation of rabbit retina. Lasers Med Sci, 2(1): 33-40.
16. Issa M, Manela-Azulay M (2010). Photodynamic therapy: a review of the literature and image documentation. An Bras Dermatol, 85:501-11.
17. Schmidt MH, Bajic DM, Reichert KW, Martin TS, Meyer GA, Whelan HT (1996). Light-emitting diodes as a light source for intraoperative photodynamic therapy. Neurosurgery, 38(3): 552-6.
18. Pourhajibagher M, Chiniforush N, Raoofian R, Ghorbanzadeh R, Shahabi S, Bahador A (2016). Effects of sub-lethal doses of photo-activated disinfection against Porphyromonas gingivalis for pharmaceutical treatment of periodontal-endodontic lesions. Photodiagnosis Photodyn Ther, 16:50-3.
19. Jagdeo J, Austin E, Mamalis A, Wong C, Ho D, Siegel DM (2018). Light‐emitting diodes in dermatology: A systematic review of randomized controlled trials. Lasers Surg Med, 50(6): 613-28
20. Paschoal MA, Santos-Pinto L, Lin M, Duarte S (2014). Streptococcus mutans photoinactivation by combination of short exposure of a broad-spectrum visible light and low concentrations of photosensitizers. Photomed Laser Surg, 32(3): 175-80.
21. Dutta S, Ongarora BG, Li H, Maria da Graca HV, Kolli BK, Chang KP (2011). Intracellular targeting specificity of novel phthalocyanines assessed in a host-parasite model for developing potential photodynamic medicine. PLoS One, 6(6): e20786.
22. Demarchi IG, Silveira TG, Ferreira IC, Lonardoni MV (2012). Effect of HIV protease inhibitors on New World Leishmania. Parasitol Int, 61(4): 538-44.
23. Lehnhardt Pires C, Rodrigues S, Bristot D, et al (2013). Evaluation of macroalgae sulfated polysaccharides on the Leishmania (L.) amazonensis promastigote. Mar Drugs, 11(3): 934-43.
24. Ramírez-Macías I, Maldonado CR, Marín C, et al (2012). In vitro anti-leishmania evaluation of nickel complexes with a triazolopyrimidine derivative against Leishmania infantum and Leishmania braziliensis. J Inorg Biochem, 112:1-9.
25. Sosa N, Pascale JM, Jiménez AI, et al (2019). Topical paromomycin for New World cutaneous leishmaniasis. PLoS Negl Trop Dis, 13(5): e0007253.
26. Proverbio D, Spada E, de Giorgi GB, Perego R (2016). Proteinuria reduction after treatment with miltefosine and allopurinol in dogs naturally infected with leishmaniasis. Vet World, 9(8): 904-8.
27. Peloi LS, Biondo CEG, Kimura E, et al (2011). Photodynamic therapy for American cutaneous leishmaniasis: the efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis. Exp Parasitol, 128(4): 353-6.
28. Escobar P, Hernández IP, Rueda CM, Martínez F, Páez E (2006). Photodynamic activity of aluminium (III) and zinc (II) phthalocyanines in Leishmania promastigotes. Biomedica, 26: 49-56.
29. Roberts A, Pimentel H, Trapnell C, Pachter L (2011). Identification of novel transcripts in annotated genomes using RNA-Seq. Bioinformatics, 27(17): 2325-9.
30. Enk CD, Fritsch C, Jonas F, et al (2003). Treatment of cutaneous leishmaniasis with photodynamic therapy. Arch Dermatol, 139(4): 432-4.
31. Demidova TN, Hamblin MR (2005). Effect of cell-photosensitizer binding and cell density on microbial photoinactivation. Antimicrob Agents Chemother, 49(6): 2329-35.
32. Singh S, Sarma S, Katiyar SP, et al (2015). Probing the molecular mechanism of hypericin-induced parasite death provides insight into the role of spermidine beyond redox metabolism in Leishmania donovani. Antimicrob Agents Chemother, 59(1): 15-24.
33. Gardner DM, Taylor VM, Cedeño DL, et al (2010). Association of acenaphthoporphyrins with liposomes for the photodynamic treatment of leishmaniasis. Photochem Photobiol, 86(3): 645-52.
34. Akilov OE, Kosaka S, O'Riordan K, et al (2006). The role of photosensitizer molecular charge and structure on the efficacy of photodynamic therapy against Leishmania parasites. Chem Biol, 13(8): 839-47.
35. JG P (2011). Assessment of Leishmania major and Leishmania braziliensis promastigote viability after photodynamic treatment with aluminum phthalocyanine tetrasulfonate (AlPcS4). J Venom Anim Toxins Incl Trop Dis, 17(3): 300-7.
36. Song D, Lindoso JAL, Oyafuso LK, et al(2011). Photodynamic therapy using methylene blue to treat cutaneous leishmaniasis. Photomed Laser Surg, 29(10): 711-5.
37. Pinto JG, de Souza Martins JF, Pereira AHC,et al (2017). Evaluation of methylene blue as photosensitizer in promastigotes of Leishmania major and Leishmania braziliensis. Photodiagnosis Photodyn Ther, 18:325-30.
38. Dutta S, Ray D, Kolli BK, Chang K-P (2005). Photodynamic sensitization of Leishmania amazonensis in both extracellular and intracellular stages with aluminum phthalocyanine chloride for photolysis in vitro. Antimicrob Agents Chemother, 49(11): 4474-84.
39. de Baltazar L, Soares B, Carneiro HC,et al (2013). Photodynamic inhibition of Trichophyton rubrum: in vitro activity and the role of oxidative and nitrosative bursts in fungal death. J Antimicrob Chemother, 68(2): 354-61.
2. Hayani K, Dandashli A, Weisshaar E (2015). Cutaneous leishmaniasis in Syria: clinical features, current status and the effects of war. Acta Derm Venereol, 95(1): 62-66.
3. van Griensven J, Balasegaram M, Meheus F, Alvar J, Lynen L, Boelaert M (2010). Combination therapy for visceral leishmaniasis. Lancet Infect Dis, 10(3): 184-94.
4. Croft SL, Coombs GH (2003). Leishmaniasis–current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol, 19(11): 502-8.
5. Ouellette M, Drummelsmith J, Papadopoulou B (2004). Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist Updat, 7(4-5): 257-66.
6. Heidari‐Kharaji M., Fallah‐Omrani V, Badirzadeh A, et al (2019). Sambucus ebulus extract stimulates cellular responses in cutaneous leishmaniasis. Parasite Immunol, 41(1): e12605.
7. Mohebali M, Kazemirad E, Hajjaran H, Kazemirad E, Oshaghi MA, Raoofian R, Teimouri A (2019). Gene expression analysis of antimony resistance in Leishmania tropica using quantitative real-time PCR focused on genes involved in trypanothione metabolism and drug transport. Arch Dermatol Res, 311(1): 9-17.
8. Kazemi-Rad E, Mohebali M, Khadem-Erfan MB, et al (2013). Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach. Exp Parasitol, 135(2): 344-49.
9. Hadighi R, Mohebali M, Boucher P, Hajjaran H, Khamesipour A, Ouellette M (2006). Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due to drug-resistant Leishmania tropica parasites. PLoS Med, 3(5): e162.
10. Taylor VM, Cedeño DL, Munoz DL, et al (2011). In vitro and in vivo studies of the utility of dimethyl and diethyl carbaporphyrin ketals in treatment of cutaneous leishmaniasis. Antimicrob Agents Chemother, 55(10): 4755-64.
11. Barbosa AF, Sangiorgi BB, Galdino SL, Barral‐Netto M, Pitta IR, Pinheiro AL (2012). Photodynamic antimicrobial chemotherapy (PACT) using phenothiazine derivatives as photosensitizers against Leishmania braziliensis. Lasers Surg Med, 44(10): 850-55.
12. Pizinger K, Cetkovska P, Kacerovska D, Kumpova M (2009). Successful treatment of cutaneous leishmaniasis by photodynamic therapy and cryotherapy. Eur J Dermatol, 19(2): 172-3.
13. Dai T, Huang Y-Y, Hamblin MR (2009). Photodynamic therapy for localized infections—state of the art. Photodiagnosis Photodyn Ther, 6(3-4): 170-88.
14. Oleinick NL, Evans HH (1998). The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat Res, 150(5 Suppl): S146-56.
15. Simpson ER, Wilson BC, Corriveau C, Murphy J (1987). Thermal damage and haematoporphyrin-derivative-sensitized photochemical damage in laser irradiation of rabbit retina. Lasers Med Sci, 2(1): 33-40.
16. Issa M, Manela-Azulay M (2010). Photodynamic therapy: a review of the literature and image documentation. An Bras Dermatol, 85:501-11.
17. Schmidt MH, Bajic DM, Reichert KW, Martin TS, Meyer GA, Whelan HT (1996). Light-emitting diodes as a light source for intraoperative photodynamic therapy. Neurosurgery, 38(3): 552-6.
18. Pourhajibagher M, Chiniforush N, Raoofian R, Ghorbanzadeh R, Shahabi S, Bahador A (2016). Effects of sub-lethal doses of photo-activated disinfection against Porphyromonas gingivalis for pharmaceutical treatment of periodontal-endodontic lesions. Photodiagnosis Photodyn Ther, 16:50-3.
19. Jagdeo J, Austin E, Mamalis A, Wong C, Ho D, Siegel DM (2018). Light‐emitting diodes in dermatology: A systematic review of randomized controlled trials. Lasers Surg Med, 50(6): 613-28
20. Paschoal MA, Santos-Pinto L, Lin M, Duarte S (2014). Streptococcus mutans photoinactivation by combination of short exposure of a broad-spectrum visible light and low concentrations of photosensitizers. Photomed Laser Surg, 32(3): 175-80.
21. Dutta S, Ongarora BG, Li H, Maria da Graca HV, Kolli BK, Chang KP (2011). Intracellular targeting specificity of novel phthalocyanines assessed in a host-parasite model for developing potential photodynamic medicine. PLoS One, 6(6): e20786.
22. Demarchi IG, Silveira TG, Ferreira IC, Lonardoni MV (2012). Effect of HIV protease inhibitors on New World Leishmania. Parasitol Int, 61(4): 538-44.
23. Lehnhardt Pires C, Rodrigues S, Bristot D, et al (2013). Evaluation of macroalgae sulfated polysaccharides on the Leishmania (L.) amazonensis promastigote. Mar Drugs, 11(3): 934-43.
24. Ramírez-Macías I, Maldonado CR, Marín C, et al (2012). In vitro anti-leishmania evaluation of nickel complexes with a triazolopyrimidine derivative against Leishmania infantum and Leishmania braziliensis. J Inorg Biochem, 112:1-9.
25. Sosa N, Pascale JM, Jiménez AI, et al (2019). Topical paromomycin for New World cutaneous leishmaniasis. PLoS Negl Trop Dis, 13(5): e0007253.
26. Proverbio D, Spada E, de Giorgi GB, Perego R (2016). Proteinuria reduction after treatment with miltefosine and allopurinol in dogs naturally infected with leishmaniasis. Vet World, 9(8): 904-8.
27. Peloi LS, Biondo CEG, Kimura E, et al (2011). Photodynamic therapy for American cutaneous leishmaniasis: the efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis. Exp Parasitol, 128(4): 353-6.
28. Escobar P, Hernández IP, Rueda CM, Martínez F, Páez E (2006). Photodynamic activity of aluminium (III) and zinc (II) phthalocyanines in Leishmania promastigotes. Biomedica, 26: 49-56.
29. Roberts A, Pimentel H, Trapnell C, Pachter L (2011). Identification of novel transcripts in annotated genomes using RNA-Seq. Bioinformatics, 27(17): 2325-9.
30. Enk CD, Fritsch C, Jonas F, et al (2003). Treatment of cutaneous leishmaniasis with photodynamic therapy. Arch Dermatol, 139(4): 432-4.
31. Demidova TN, Hamblin MR (2005). Effect of cell-photosensitizer binding and cell density on microbial photoinactivation. Antimicrob Agents Chemother, 49(6): 2329-35.
32. Singh S, Sarma S, Katiyar SP, et al (2015). Probing the molecular mechanism of hypericin-induced parasite death provides insight into the role of spermidine beyond redox metabolism in Leishmania donovani. Antimicrob Agents Chemother, 59(1): 15-24.
33. Gardner DM, Taylor VM, Cedeño DL, et al (2010). Association of acenaphthoporphyrins with liposomes for the photodynamic treatment of leishmaniasis. Photochem Photobiol, 86(3): 645-52.
34. Akilov OE, Kosaka S, O'Riordan K, et al (2006). The role of photosensitizer molecular charge and structure on the efficacy of photodynamic therapy against Leishmania parasites. Chem Biol, 13(8): 839-47.
35. JG P (2011). Assessment of Leishmania major and Leishmania braziliensis promastigote viability after photodynamic treatment with aluminum phthalocyanine tetrasulfonate (AlPcS4). J Venom Anim Toxins Incl Trop Dis, 17(3): 300-7.
36. Song D, Lindoso JAL, Oyafuso LK, et al(2011). Photodynamic therapy using methylene blue to treat cutaneous leishmaniasis. Photomed Laser Surg, 29(10): 711-5.
37. Pinto JG, de Souza Martins JF, Pereira AHC,et al (2017). Evaluation of methylene blue as photosensitizer in promastigotes of Leishmania major and Leishmania braziliensis. Photodiagnosis Photodyn Ther, 18:325-30.
38. Dutta S, Ray D, Kolli BK, Chang K-P (2005). Photodynamic sensitization of Leishmania amazonensis in both extracellular and intracellular stages with aluminum phthalocyanine chloride for photolysis in vitro. Antimicrob Agents Chemother, 49(11): 4474-84.
39. de Baltazar L, Soares B, Carneiro HC,et al (2013). Photodynamic inhibition of Trichophyton rubrum: in vitro activity and the role of oxidative and nitrosative bursts in fungal death. J Antimicrob Chemother, 68(2): 354-61.
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| Issue | Vol 50 No 10 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v50i10.7514 | |
| Keywords | ||
| Leishmania major In vitro Photodynamic therapy (PDT) Toluidine blue O (TBO) | ||
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How to Cite
1.
Najm M, Pourhajibagher M, Badirzadeh A, Razmjou E, Alipour M, Khoshmirsafa M, Bahador A, Hadighi R. Photodynamic Therapy Using Toluidine Blue O (TBO) Dye as a Photosensitizer against Leishmania major. Iran J Public Health. 2021;50(10):2111-2120.
