Impact of UVC radiation on interaction of selected antifungal drugs (azole derivatives) with model DPPH free radical
Paweł Ramos 1  
,   Piotr Pepliński 1  
,   Barbara Pilawa 1  
 
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Department of Biophysics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
CORRESPONDING AUTHOR
Paweł Ramos   

Katedra i Zakład Biofizyki, Wydział Nauk Farmaceutycznych w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, ul. Jedności 8, 41-200 Sosnowiec
 
Ann. Acad. Med. Siles. 2020;74:77–90
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Fungal lesions are accompanied by inflammation, during which large amounts of free radicals are formed. Antifungal drugs, which have an additional antioxidant effect, could contribute to a faster recovery. An important role in ensuring effective and safe pharmacotherapy of fungal lesions is played by proper drug storage and appropriate patient actions during treatment. Ultraviolet radiation can generate free radicals in a drug due to photolysis. A drug containing free radicals may cause toxic effects in the body. The aim of the study was to research the antioxidant properties of selected antifungal drugs of azole derivatives. Addi-tionally, the impact of UVC radiation on the tested drugs and their interaction with the DPPH free radical was studied.

Material and methods:
The tested azole samples were exposed to 24-hour UVC radiation. The interaction of drug samples with a model DPPH free radical, before and after exposure to UV radiation, was studied. UV-Vis spectroscopy and colourimetry in the CIE Lab colour analysis system were used as the research techniques.

Results:
Among the initial samples of the tested drugs only ketoconazole interacted with the DPPH free radical, causing its extinction. Exposure to UVC radiation increased the antioxidant properties in ketoconazole and miconazole. The CIE Lab parameters, UV spectra and interaction kinetics of those two drugs with DPPH were different after UVC exposure, which may indicate changes in ketoconazole and miconazole. The highest stability to ultraviolet radiation was shown by fluconazole, whose CIE Lab parameters, UV spectra and interaction with DPPH did not change after exposure of the sample to light radiation.

Conclusions:
The research using UV-Vis spectrophotometry and colourimetry enabled the impact of UVC radiation on selected antifungal drugs to be evaluated, including evaluation of their interaction with the model DPPH free radical. It is recommended to protect ketoconazole and miconazole from exposure to light. It is also advisable to protect patients from the sun during pharmacotherapy with these drugs.

 
REFERENCES (40)
1.
Janiec K.W., Pytlik M., Cegieła U. Leki układu immunologicznego (leki immunotropowe). W: Kompendium farmakologii. Red. W. Janiec. Wydawnictwo Lekarskie PZWL. Warszawa 2016, s. 435–440.
 
2.
Cegieła U., JaniecW., Pytlik M. Leki stosowane w leczeniu nowotworów. W: Kompendium farmakologii. Red. W. Janiec. Wydawnictwo Lekarskie PZWL. Warszawa 2016, s. 451–454.
 
3.
Janiec W., Nowińska B., Śliwiński L. Leki stosowane w zakażeniach i chorobach inwazyjnych. W: Kompendium farmakologii. Red. W. Janiec. Wydawnictwo Lekarskie PZWL. Warszawa 2016, s. 510–515.
 
4.
Gomułka W.S. Farmakodynamika leków stosowanych w zakażeniach i chorobach inwazyjnych. W: Farmakodynamika. Red. W. Janiec. Wydawnictwo Lekarskie PZWL. Warszawa 2008; s. 880–888.
 
5.
Rewerski W., Filipiak K.J. Leki przeciwgrzybicze. W: Farmakologia. Red. W. Kostowski, Z. Herman. Wydawnictwo Lekarskie PZWL. Warszawa 2004, s. 359–366.
 
6.
Tarchalska-Kryńska B. Farmakologia układu immunologicznego. W: Farmakologia. Red. W. Kostowski, Z. Herman. Wydawnictwo Lekarskie PZWL. Warszawa 2004, s. 390–444.
 
7.
Abbas N., Arshad M.S., Hussain A., Irfan M., Ahsan M., Rasool M.F., ur Rehman M.H. Development and validation of a spectroscopic method for the simultaneous analysis of miconazole nitrate and hydrocortisone acetate in pharmaceutical dosage form. Trop. J. Pharm. Res. 2017; 16(2): 413–420.
 
8.
Lamb D.C., Warrilow A.G., Rolley N.J., Parker J.E., Nes W.D., Smith S.N., Kelly D.E., Kelly S.L. Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51). Antimicrob. Agents Chemother. 2015; 59(8): 4707–4713, doi: 10.1128/AAC.00476-15.
 
9.
Chen Z.F., Ying G.G., Jiang Y.X., Yang B., Lai H.J., Liu Y.S., Pan C.G., Peng F.Q. Photodegradation of the azole fungicide fluconazole in aqueous solution under UV-254: kinetics, mechanistic investigations and toxicity evaluation Water Res. 2014; 52: 83–91, doi: 10.1016/j.watres.2013.12.039.
 
10.
Girish M.B., Patil P.A. The influence of some azoles on wound healing in albino rats. Indian J. Pharmacol. 2005; 37(4): 247–250, doi: 10.4103/0253-7613.16572.
 
11.
Jakubowicz O., Łuczkowska M., Żaba R., Adamski Z. Tinea cutis glabrae: causes of diagnostic challenge. Postepy Dermatol. Alergol. 2014; 31(6): 421–424, doi: 10.5114/pdia.2014.40950.
 
12.
Yoshioka S., Stella V.J. Stability of drugs and dosage forms. Kluwer Academic Publishers. New York, Boston, Dordrecht, London, Moscow 2002.
 
13.
Ahmad I., Ahmed S. Anwar Z., Sheraz M.A., Sikorski M. Photostability and Photostabilization of Drugs and Drug Products. Int. J. Photoenergy 2016; ID 8135608: 1–19, doi: 10.1155/2016/8135608.
 
14.
Bartosz G. Strategia ataku. W: Bartosz G. Druga twarz tlenu. Wydawnictwo Naukowe PWN. Warszawa 2003, s. 58–61, 84–91, 99–119.
 
15.
Castro G., Casado J., Rodríguez I., Ramil M., Ferradás A., Cela R. Time-of-flight mass spectrometry assessment of fluconazole and climbazole UV and UV/H2O2 degradability: Kinetics study and transformation products elucidation. Water Res. 2016; 88: 681–690, doi: 10.1016/j.watres.2015.10.053.
 
16.
Thoma K., Kübler N. Photostability of antifungal agents. 2. Photostability of polyene antibiotics. Pharmazie 1997; 52(4): 294–302.
 
17.
Chen Z.F., Ying G.G. Occurrence, fate and ecological risk of five typical azole fungicides as therapeutic and personal care products in the environment: A review. Environ. Int. 2015; 84: 142–153, doi: 10.1016/j.envint.2015.07.022.
 
18.
Gwoździński M. Wolne rodniki, antyutleniacze oraz uszkodzenia lipidów, białek i kwasów nukleinowych. W: Jóźwiak Z., Bartosz G. Biofizyka. Wydawnictwo Naukowe PWN. Warszawa 2005, s. 423–451.
 
19.
Tirzitis G., Bartosz G. Determination of antiradical and antioxidant activity: basic principles and new insights. Acta Biochim. Pol. 2010; 57(2): 139–142.
 
20.
Zvezdanović J.B., Marković D.Z., Cvetković D.J., Stanojević J.S. UV-induced change in the antioxidant activity of quercetin toward benzophenone-initiated lipid peroxidation. J. Serb. Chem. Soc. 2012; 77(11): 1571–1588.
 
21.
Jurzak M., Ramos P., Pilawa B. The influence of genistein on free radicals in normal dermal fibroblasts and keloid fibroblasts examined by EPR spectroscopy. Med. Chem. Res. 2017; 26(6): 1297–1305, doi: 10.1007/s00044-017-1848-3.
 
22.
Łucka-Sobstel B. Leki przeciwgrzybicze. W: Chemia leków. Red. A. Zejc, M. Gorczyca. Wydawnictwo Lekarskie PZWL. Warszawa 2009, s. 703–706.
 
23.
Ketokonazol (karta charakterystyki substancji), https://www.sigmaaldrich. com/catalog/product/sial/k0600000?lang=pl& region=PL [dostęp: 10.11.2016].
 
24.
Mikonazol (karta charakterystyki substancji), https://www.sigmaaldrich. com/catalog/product/sial/m1900000?lang=pl& region=PL [dostęp: 10.11.2016].
 
25.
Flukonazol (karta charakterystyki substancji), https://www.sigmaaldrich. com/catalog/product/sial/y0000557?lang=pl& region=PL [dostęp: 04.10.2016].
 
26.
Molyneux P. The use of the stable free radical diphenylpicrylhydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin J. Sci. Technol. 2004; 26(2): 211–219.
 
27.
Rój A., Przybyłowski P. Ocena barwy jogurtów naturalnych. Bromat. Chem. Toksykol. 2012; 45(3): 813–816.
 
28.
Harbourne N., Jacquier J.C., O’Riordan D. Optimisation of the extraction and processing conditions of chamomile (Matricaria chamomilla L.) for incorporation into a beverage. Food Chem. 2009; 115(1): 15–19, doi: 10.1016/j.foodchem.2008.11.044.
 
29.
Suwiński J. Łączne użycie metod spektroskopowych w celu ustalenia struktury związku. W: Zieliński W., Rajca A. Metody spektroskopowe i ich zastosowanie do identyfikacji związków organicznych. Wydawnictwo Naukowo-Techniczne. Warszawa 1995, s. 520–553.
 
30.
Alizadeh N., Rezakhani Z. Extractive spectrophotometric determination of ketoconazole, clotrimazole and fluconazole by ion-pair complex formation with bromothymol blue and picric acid. J. Chil. Chem. Soc. 2012; 57(2): 1104–1108.
 
31.
Wiseman H., Smith C., Arnstein H.R., Halliwell B., Cannon M. The antioxidant action of ketoconazole and related azoles: comparison with tamoxifen and cholesterol. Chem. Biol. Interact. 1991; 79(2): 229–243.
 
32.
Kus C., Sozudonmez F, Can-Eke B., Coban T. Antioxidant and antifungal properties of benzimidazole derivatives. Z. Naturforsch. C. J. Biosci. 2010; 65(9–10): 537–542.
 
33.
Stanjek-Cichoracka A., Żegleń S., Ramos P., Pilawa B., Wojarski J. Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals. J. Clin. Pharm. Ther. 2018; 43(3): 385–392, doi: 10.1111/jcpt.12668.
 
34.
Skiba M., Skiba-Lahiani M., Marchais H., Duclos R., Arnaud P. Stability assessment of ketoconazole in aqueous formulations. Int. J. Pharm. 2000; 198(1): 1–6.
 
35.
Stohs S.J. The role of free radicals in toxicity and disease. J. Basic. Clin. Physiol. Pharmacol. 1995; 6(3–4): 205–228.
 
36.
Halliwell B., Gutteridge J.M. Reactive species can be poisonous. In: Halliwell B., Gutteridge J.M. Free radicals in biology and medicine. Oxford University Press. United Kingdom 2015, p. 463–510.
 
37.
Staub I., Flores L., Gosmann G., Pohlmann A., Fröehlich P.E., Schapoval E.E., Bergold A.M. Photostability studies of ketoconazole: isolation and structural elucidation of the main photodegradation products. Lat. Am. J. Pharm. 2010; 29(7): 1100–1106.
 
38.
Liu W.R., Ying G.G., Zhao J.L., Liu Y.S., Hu L.X., Yao L., Liang Y.Q., Tian F. Photodegradation of the azole fungicide climbazole by ultraviolet irradiation under different conditions: Kinetics, mechanism and toxicity evaluation. J. Hazard. Mater. 2016; 318: 794–801, doi: 10.1016/j.jhazmat.2016.06.033.
 
39.
Da Silva J.P., Da Silva A.M., Khmelinskii I.V., Martinho J.M., Vieira Ferreira L.F. Photophysics and photochemistry of azole fungicides: triadimefon and triadimenol. J. Photochem. Photobiol. A 2001; 142: 31–37.
 
40.
Ahmed S., Anwar N., Sheraz M.A., Ahmad I. Degradation kinetics of sulfacetamide sodium in ophthalmic preparations in dark and light. Sci. Technol. Dev. 2017; 36(4): 206–210, doi: 10.3923/std.2017.206.210.
 
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