Effects of Vitamin D on doxorubucin-induced lung injury and TRPM2 immunoreactivity in rats

Authors

Keywords:

Doxorubucin, Lung, Oxidative stress, Transient receptor potential melastatin 2, Vitamin D

Abstract

Aim: Although doxorubicin (DOX) is a commonly used chemotherapeutic agent, it causes significant toxic side effects on many organs. This study aims to investigate the effects of vitamin D (VD) on DOX-induced lung injury and expression of transient receptor potential melastatin 2 (TRPM2), a Ca2 + permeable cation channel. Methods: A total of 24 Wistar albino rats were separated into four groups of six rats, as follows: The control group received no medications. The VD group received 200 IU/kg VD via an oral dropper (o.d.) for 14-days. DOX group received a single dose of 10 mg/kg DOX intraperitoneally (i.p.) on day 8. DOX+VD group was administered 200 IU/kg VD via an o.d. for 14-days, and a single dose of 10 mg/kg DOX i.p. on day 8. At the end of the experiment, lung and serum samples from all rats were collected. Masson’s trichrome staining and streptavidin-biotin-peroxidase complex were applied to the lung tissue sections. Serum total antioxidant status (TAS) and total oxidant status (TOS) were assessed by enzyme-linked immunosorbent assay (ELISA) method. Results: Histopathological damage was observed in the DOX group compared to the control group, and biochemical and immunohistochemical evaluation revealed that TOS level and TRPM2 expression increased while TAS level decreased significantly (P<0.001). Additionally, compared to the DOX group VD administration significantly reversed these values in the DOX+VD group (P<0.001). Conclusion: VD showed a protective effect on lung damage induced by DOX. Our data also suggest that TRPM2 channel may have a role in the pathophysiology of DOX-induced lung damage.

Downloads

Download data is not yet available.

References

Chegaev K, Riganti C, Rolando B, Lazzarato L, Gazzano E, Guglielmo S, et al. Doxorubicin-antioxidant co-drugs. Bioorg Med Chem Lett. 2013;23(19):5307-10. doi: 10.1016/j.bmcl.2013.07.070.

Zheng J, Lee HC, Bin Sattar MM, Huang Y, Bian JS. Cardioprotective effects of epigallocatechin-3-gallate against doxorubicin-induced cardiomyocyte injury. Eur J Pharmacol. 2011;652(1-3):82-8. doi: 10.1016/j.ejphar.2010.10.082.

Munnier E, Cohen-Jonathan S, Hervé K, Linassier C, Souce´ M, Dubois P, et al. Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity. J Nanoparte Res. 2011;13(3):959-71. doi: 10.1007/s11051-010-0093-1.

Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57(7):727–41. doi: 10.1016/s0006-2952(98)00307-4.

Singal PK, Siveski-Iliskovic N, Hill M, Thomas TP, Li T. Combination therapy with probucol prevents adriamycininduced cardiomyopathy. J Mol Cell Cardiol. 1995;27(4):1055-63. doi: 10.1016/0022-2828(95)90074-8.

Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, et al. Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 2011;21(7):440–6. doi: 10.1097/FPC.0b013e32833ffb56.

Matsumoto K, Takagi K, Kato A, Ishibashi T, Mori Y, Tashima K, et al. Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral nociception and hypersensitivity. Exp Neurol. 2016;285(Pt A):41-50. doi: 10.1016/j.expneurol.2016.09.001.

Wehage E, Eisfeld J, Heiner I, Jüngling E, Zitt C, Lückhoff A. Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose. J Biol Chem. 2002;277(26):23150–6. doi: 10.1074/jbc.M112096200.

Wilkinson JA, Scragg JL, Boyle JP, Nilius B, Peers C. H2O2- stimulated Ca+2 influx via TRPM2 is not the sole determinant of subsequent cell death. Pflugers Arch. 2008;455(6):1141-51. doi: 10.1007/s00424-007-0384-2.

Caprio M, Mammi C, Rosano GM. Vitamin D: A novel player in endothelial function and dysfunction. Arch Med Sci. 2012;8(1):4-5. doi: 10.5114/aoms.2012.27271.

Wiseman, H. Vitamin D is a membrane antioxidant. Ability to inhibit iron‐dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS letters. 1993;326(1-3):285-8. doi: 10.1016/0014-5793(93)81809-e.

Timar A, Saberi-Karimian M, Ghazizadeh H, Parizadeh SMR, Sabbaghzadeh R, Emadzadeh M, et al. Evaluation of the serum prooxidant-antioxidant balance before and after vitamin D supplementation in adolescent Iranian girls. Adv Med Sci. 2019;64(1):174-80. doi: 10.1016/j.advms.2018.10.004.

Wimalawansa SJ. Vitamin D deficiency: Effects on oxidative stress, epigenetics, gene regulation, and aging. Biology. 2019;8(2):30. doi: 10.3390/biology8020030.

Olson RD, Mushlin PS. Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. The FASEB Journal. 1990;4(13):3076–86.

Oz E, Erbaş D, Sürücü HS, Düzgün E. Prevention of doxorubicin-induced cardiotoxicity by melatonin. Mol Cell Biochem. 2006;282(1-2):31-7. doi: 10.1007/s11010-006-1153-9.

Take G, Yamaç D, Ozoğul C, Erdogan D. Ultrastructural damage in lung tissues in rats treated with doxorubicin and paclitaxel. Adv Ther. 2008;25(2):115-22. doi: 10.1007/s12325-008-0015-0.

Minchin RF, Johnston MR, Aiken MA, Boyd MR. The pharmacokinetics of doxorubicin in isolated lung of dog and main perfused in vivo. J Pharmacol Exp Ther. 1984;229(1):193-8.

Zosky GR, Berry LJ, Elliot JG, James AL, Gorman S, Hart PH. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Respir Crit Care Med. 2011;183(10):1336-43. doi: 10.1164/rccm.201010-1596OC.

Tao S, Zhang H, Xue L, Jiang X, Wang H, Li B, et al. Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner. Environ Toxicol. 2019;34(5):594-609. doi: 10.1002/tox.22726.

Keles H. Yalcin A, Aydin H. Protective effect of Vitamin D on imidacloprid-induced testicular injury in rats. Arch Med Sci. 2019;15(1). doi: 10.5114/aoms.2019.86776.

Yalcin A, Aydin H, Turk A, Dogukan M, Eser N, Onderci M, et al. Vitamin D: An effective way to combat methotrexate-induced testis injury. Medicine, 2020;9(4):998-1003. doi: 10.5455/medscience.2020.10.222.

Dietrich A, Steinritz D, Gudermann T. Transient receptor potential (TRP) channels as molecular targets in lung toxicology and associated diseases. Cell calcium. 2017;67:123-37. doi: 10.1016/j.ceca.2017.04.005.

Naziroğlu M, Lückhoff A. Effects of antioxidants on calcium influx through TRPM2channels in transfected cells activated by hydrogen peroxide. J Neurol Sci. 2008;270(1-2):152-8. doi: 10.1016/j.jns.2008.03.003.

Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, et al. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell. 2002;9(1):163-73. doi: 10.1016/s1097-2765(01)00438-5.

Lange I, Yamamoto S, Partida-Sanchez S, Mori Y, Fleig A, Penner R. TRPM2 functions as a lysosomal Ca2+-release channel in beta cells. Sci Signal. 2009;2(71):ra23. doi: 10.1126/scisignal.2000278.

Kuloğlu T, Kocaman N. Determination of Renal TRPM2 Channels Immunoreactivities in Enalapril Administrated Diabetic Rats. F.Ü. Sağ. Bil. Tıp Derg. 2013;27(1):27-32. (In Turkish with English abstract)

Artaş G, Kuloglu, T. The Effects of Losartan on TRPV1 and TRPM2 Channels at Diabetic Rat Kidney Tissue Fırat Tıp Dergisi. 2014;19(3):116-21. (In Turkish with English abstract)

Celik O, Nazıroğlu, M. Melatonin modulates apoptosis and TRPM2 channels in transfected cells activated by oxidative stress. Physiol behav. 2012;107(3):458-65. doi: 10.1016/j.physbeh.2012.09.013.

Tasaka S, Amaya F, Hashimoto S, Ishizaka A. Roles of oxidants and redox signaling in the pathogenesis of acute respiratory distress syndrome. Antioxid Redox Signal. 2008;10(4):739–53. doi: 10.1089/ars.2007.1940.

Miller BA, Zhang W. Transient Receptor Potential Channels. Dordrecht: Springer; 2011. Chapter 29, TRP channels as mediators of oxidative stress; p. 531-44.

Feng JF, Lu L, Dai CM, Wang D, Yang YH, Yang YW, et al. Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages. Clin Biochem. 2016;49(9):692-8. doi: 10.1016/j.clinbiochem.2016.02.005.

Demirpençe O, Sevim B, Yıldırım M, Nurlu NA, Mert D, Evliyaoğlu O. Serum paraoxonase, TAS, TOS and ceruloplasmin in brucellosis. Int J Clin Exp Med. 2014;7(6):1592–7.

Öztürk E, Kaymak E, Akin AT, Karabulut D, Ünsal HM, Yakan B. Thymoquinone is a protective agent that reduces the negative effects of doxorubicin in rat testis. Hum Exp Toxicol. 2020;39(10):1364-73. doi: 10.1177/0960327120924108.

Karabulut D, Ozturk E, Kaymak E, Akin AT, Yakan B. Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. J Biochem Mol Toxicol. 2020:e22618. doi: 10.1002/jbt.22618.

Gozel N, Genc F, Ozdemir FA, Kuloglu T, Kaya N, Yalcin MH, et al. Effects of Vitamin D on matrix metalloproteinase 9 and apoptosis in experimental diabetic rat kidney tissue. Fresenius Environ Bull. 2018;27(5 A):3766-75.

Downloads

Published

2020-12-01

Issue

Section

Research Article

How to Cite

1.
Yalçın A, Türk A, Aydın H, Yılmaz E, Çelik İbrahim S, Üçkardeş F. Effects of Vitamin D on doxorubucin-induced lung injury and TRPM2 immunoreactivity in rats. J Surg Med [Internet]. 2020 Dec. 1 [cited 2022 Nov. 30];4(12):1236-9. Available from: https://jsurgmed.com/article/view/842133