İlaçlar İle İndüklenen Fosfolipidozis ve Katyonik Amfifilik İlaçlar
Fosfolipidozis bir lipid depo bozukluğudur ve karaciğer, böbrek, beyin ve akciğer gibi dokularda fosfolipidlerin aşırı birikimi ile karakterizedir. Hücrelerde fosfolipid birikimi fosfolipidozisin önemli histopatolojik biyobelirteçleri olarak da kullanılan köpüklü sitoplazmaya, sitoplazmik vakuollere ve lamellar cisimciklerin oluşmasına neden olur. Katyonik amfifilik ilaçlar (KAİ’lar)’ın fosfolipidozis geliştirme potansiyellerinin olduğu bilinmektedir. KAİ’lar hidrofobik bir halka yapısı ile amin grubu içeren hidrofilik bir yan zincire sahiptirler. Sahip oldukları hidrofobik yapı sayesinde membranları kolaylıkla geçerler ve lizozomların asit ortamında katyonik hale geçip lizozomlarda tutulurlar. İlaçlar ile indüklenen fosfolipidozisin fonksiyonel olarak nasıl bir etkiye neden olduğu ve mekanizması tam olarak bilinmemektedir. Ancak, fosfolipidozis ile değişmiş hücre fonksiyonları ve hücre ölümü arasında olası bir ilişki bulunması nedeniyle toksik bir yanıt oluşturduğu düşünülmekte ve fosfolipidozis gelişimi advers etki olarak kabul edilmektedir.
Drug Induced Phospholipidosis and Cationic Amphiphilic Drugs
Phospholipidosis is a lipid storage disorder and it is characterized by excessive accumulation of phospholipids in tissues such as liver, kidney, brain and lung. Accumulation of phospholipid in the cells leads to foamy cytoplasm, cytoplasmic vacuoles and lamellar bodies which are also used as important histopathological biomarkers of phospholipidosis. Cationic amphiphilic drugs (CADs) are known to have a potential for development of phospholipidosis. CADs have a hydrophobic ring structure and hydrophilic side chain which contains an amine group. Because of their hydrophobic structure, CADs can pass through the membrans easily and get trapped in the lysosomes thereby become cationic in the acidic environment of lysosomes. The mechanism and the functional effects of drug induced phospholipidosis are not fully understood. However, phospholipidosis is thought to be a toxic response due to a relationship between cell death and altered cell functions, and the development of phospholipidosis is considered as an adverse reaction.
___
- 1. Bagshaw RD, Mahuran DJ, Callahan JW: A proteomic analysis of
lysosomal integral membrane proteins reveals the diverse composition
of the organelle. Molecular & Cellular Proteomics. 2005,
4(2):133-143.
- 2. Walkley SU: Pathogenic cascades in lysosomal disease-why so
complex? Journal of Inherited Metabolic Disease 2009, 32(2):181-
189.
- 3. Aits S, Jäättelä M: Lysosomal cell death at a glance. Journal of Cell
Science 2013, 126:1905-1912.
- 4. Ohsumi Y: Molecular dissection of autophagy: two ubiquitin-like
systems. Nature Reviews Molecular Cell Biology 2001, 2(3):211-
216.
- 5. Levine B: Eating oneself and uninvited guests: autophagy-related
pathways in cellular defense. Cell 2005, 120(2):159-162.
- 6. Nonoyama T, Fukuda R: Drug-induced phospholipidosis-pathological
aspects and its prediction. Journal of Toxicologic Pathology
21(1):9-24.
- 7. Halliwell WH: Cationic amphiphilic drug-induced phospholipidosis.
Toxicologic Pathology 1997, 25(1):53-60.
- 8. Anderson N, Borlak J: Drug‐induced phospholipidosis. FEBS Letters
2006, 580(23):5533-5540.
- 9. van de Water F, Havinga J, Ravesloot W, Horbach G, Schoonen W:
High content screening analysis of phospholipidosis: validation of a
96-well assay with CHO-K1 and HepG2 cells for the prediction of in
vivo based phospholipidosis. Toxicology In Vitro 2011, 25(8):1870-
1882.
- 10. Reasor MJ, Kacew S: Drug-induced phospholipidosis: are there
functional consequences? Experimental Biology and Medicine 2001,
226(9):825-830.
- 11. Sawada H, Takami K, Asahi S: A toxicogenomic approach to
drug-induced phospholipidosis: analysis of its induction mechanism
and establishment of a novel in vitro screening system. Toxicological
Sciences 2005, 83(2):282-292.
- 12. Ikeda K, Hirayama M, Hirota Y, Asa E, Seki J, Tanaka Y: Drug-induced
phospholipidosis is caused by blockade of mannose 6-phosphate
receptor-mediated targeting of lysosomal enzymes. Biochemical and
Biophysical Research Communications 2008, 377(1):268-274.
- 13. Nadanaciva S, Lu S, Gebhard DF, Jessen BA, Pennie WD, Will
Y: A high content screening assay for identifying lysosomotropic
compounds. Toxicology In Vitro 2011, 25(3):715-723.
- 14. Reasor MJ, Hastings KL, Ulrich RG: Drug-induced phospholipidosis:
issues and future directions. Expert Opinion on Drug Safety
2006, 5(4):567-583.
- 15. Shayman JA, Abe A: Drug induced phospholipidosis: an acquired
lysosomal storage disorder. B Biochimica et Biophysica Acta
(BBA)-Molecular and Cell Biology of Lipids 2013, 1831(3):602-
611.
- 16. Cartwright ME, Petruska J, Arezzo J, Frank D, Litwak M, Morrissey
RE, et al.: Phospholipidosis in neurons caused by posaconazole,
without evidence for functional neurologic effects. Toxicologic
Pathology 2009, 37(7):902-910.
- 17. Hirode M, Ono A, Miyagishima T, Nagao T, Ohno Y, Urushidani
T: Gene expression profiling in rat liver treated with compounds
inducing phospholipidosis. Toxicology and Applied Pharmacology
2008, 229(3):290-299.
- 18. Sadrich N, The regulatory challenge of drug-induced phospholipidosis.
FDA Pharmaceutical Science and Clinical Pharmacology
Advisory Committee meeting; Apr 14, 2010.
- 19. Hutchinson TH, Mahshid Y, Jönsson R, Björklund C, Kenne K:
Proteomic analysis of phospholipidosis in citalopram treated U937
cells–support for the cholesterol biosynthesis hypothesis. Toxicology
In Vitro 2008, 22(5):1198-1204.
- 20. Lüllmann‐Rauch R, Nässberger L: Citalopram‐induced generalized
lipidosis in rats. Acta Pharmacologica et Toxicologica 1983,
52(3):161-167.
- 21. Wold JS, Joost RR, Griffing WJ, Marroquin F, Harris P: Phospholipid
accumulation in rats produced by fluoxetine and chlorphentermine.
Toxicology and Applied Pharmacology 1976, 37:118-119.
- 22. Gonzalez-Rothi RJ, Zander DS, Ros PR: Fluoxetine hydrochloride
(Prozac)-induced pulmonary disease. CHEST Journal. 1995,
107(6):1763-1765.
- 23. Lüllmann-Rauch R, Reil G-H: Chlorphentermine-induced lipidosislike
ultrastructural alterations in lungs and adrenal glands of
several species. Toxicology and Applied Pharmacology 1974, 30(3):
408-421.
- 24. Gloster J, Heath D, Hasleton P, Harris P: Effect of chlorphentermine
on the lipids of rat lungs. Thorax 1976, 31(5):558-564.
- 25. Lüllmann-Rauch R: Retinal lipidosis in albino rats treated with
chlorphentermine and with tricyclic antidepressants. Acta Neuropathologica
1976, 35(1):55-67.
- 26. Lüllmann-Rauch R: Lipidosislike renal changes in rats treated with
chlorphentermine or with tricyclic antidepressants. Virchows Archiv
B Cell Pathology 1975, 18(1):51-60.
- 27. Kacew S: Alterations in newborn and adult rat lung morphology and
phospholipid levels after chlorcyclizine or chlorphentermine treatment.
Toxicology and Applied Pharmacology 1982, 65(1):100-108.
- 28. Kacew S: Gentamicin or chlorphentermine induction of phospholipidosis
in the developing organism: role of tissue and species in
manifestation of toxicity. Journal of Pharmacology and Experimental
Therapeutics 1985, 232(1):239-243.
- 29. Reasor MJ, Koshut RA: Augmentation in antioxidant defense
mechanisms in rat alveolar macrophages following induction of
phospholipidosis with chlorphentermine. Toxicology and Applied
Pharmacology 1980, 55(2): 334-341.
- 30. Reasor MJ, Walker ER: Recovery from chlorphentermine-induced
phospholipidosis in rat alveolar macrophages: Morphological features.
Experimental and Molecular Pathology 1981, 35(3):370-379.
- 31. Reasor MJ, Castranova V: Recovery from chlorphentermine-induced
phospholipidosis in rat alveolar macrophages: Biochemical and
cellular features. Experimental and Molecular Pathology 1981,
35(3):359-369.
- 32. Reasor MJ, Koshut RA, Castranova V: Biochemical characteristics
of rat alveolar macrophages with chlorphentermine-induced
phospholipidosis: Variations with increasing cell size. Experimental
and Molecular Pathology 1979, 31(2):297-307.
- 33. Lüllmann-Rauch R: Lipidosis-like alterations in spinal cord and
cerebellar cortex of rats treated with chlorphentermine or tricylic
antidepressants. Acta Neuropathologica 1974, 29(3):237-249.
- 34. Frisch W, Lüllmann-Rauch R: Differential effects of chloroquine and
of several other amphiphilic cationic drugs upon rat choroid plexus.
Acta Neuropathologica 1979, 46(3):203-208.
- 35. Lüllmann-Rauch R, Reil G-H: Fenfluramine-induced ultrastructural
alterations in tissues of rats and guinea pigs. Naunyn-Schmiedeberg's
Archives of Pharmacology 1974, 285(2):175-184.
- 36. Ryrfeldt Å: Drug-induced inflammatory responses to the lung.
Toxicology Letters 2000, 112-113:171-176.
- 37. Martin W, Kachel D, Vilen T, Natarajan V: Mechanism of phospholipidosis
in amiodarone pulmonary toxicity. Journal of Pharmacology
and Experimental Therapeutics 1989, 251(1): 272-278.
- 38. Reasor MJ, Ogle CL, Walker ER, Kacew S: Amiodarone-induced
Phospholipidosis in Rat Alveolar Macrophages1-3. American Review
of Respiratory Disease 1988, 137:510-518.
- 39. Riva E, Marchi S, Pesenti A, Bizzi A, Cini M, Veneroni E, et al.:
Amiodarone induced phospholipidosis biochemical, morphological
and functional changes in the lungs of rats chronically treated with
amiodarone. Biochemical Pharmacology 1987, 36(19):3209-3214.
- 40. Heath M, Costa-Jussa F, Jacobs J, Jacobson W: The induction of
pulmonary phospholipidosis and the inhibition of lysosomal phospholipases
by amiodarone. British Journal of Experimental Pathology
1985, 66(4):391-397.
- 41. Mortuza GB, Neville WA, Delaney J, Waterfield CJ, Camilleri
P: Characterisation of a potential biomarker of phospholipidosis
from amiodarone-treated rats. Biochimica et Biochimica et Biophysica
Acta (BBA)-Molecular and Cell Biology of Lipids. 2003,
1631(2):136-146.
- 42. Goldman I, Winkler M, Raper S, Barker M, Keung E, Goldberg H,
et al.: Increased hepatic density and phospholipidosis due to amiodarone.
American Journal of Roentgenology 1985, 144(3):541-546.
- 43. Delaney J, Neville WA, Swain A, Miles A, Leonard MS, Waterfield
CJ: Phenylacetylglycine, a putative biomarker of phospholipidosis:
its origins and relevance to phospholipid accumulation using amiodarone
treated rats as a model. Biomarkers. 2004, 9(3):271-290.
- 44. Ágoston M, Örsi F, Fehér E, Hagymási K, Orosz Z, Blázovics A, et
al.: Silymarin and vitamin E reduce amiodarone-induced lysosomal
phospholipidosis in rats. Toxicology. 2003, 190(3):231-241.
- 45. D'Amico DJ, Kenyon KR, Ruskin JN: Amiodarone keratopathy:
drug-induced lipid storage disease. Archives of Ophthalmology
1981, 99(2):257-261.
- 46. Adams P, Holt D, Storey G, Morley A, Callaghan J, Campbell R:
Amiodarone and its desethyl metabolite: tissue distribution and
morphologic changes during long-term therapy. Circulation 1985,
72(5):1064-1075.
- 47. Reasor MJ, McCloud CM, Beard TL, Ebert DC, Kacew S, Gardner
MF, et al.: Comparative evaluation of amiodarone-induced phospholipidosis
and drug accumulation in Fischer-344 and Sprague-Dawley
rats. Toxicology 1996, 106(1-3):139-147.
- 48. Marchlinski FE, Gansler TS, Waxman HL, Josephson ME: Amiodarone
pulmonary toxicity. Annals of Internal Medicine 1982;
97(6):839-845.
- 49. Kleiner DE. Amiodarone-Induced Phospholipidosis. In: Ferrell LD,
Kakar S (eds) Liver pathology. Demos Medical Publishing; New
York, USA. 2011: pp 237-239.
- 50. Guigui B, Perrot S, Berry JP, Fleury‐Feith J, Martin N, Métreau JM, et
al.: Amiodarone‐induced hepatic phospholipidosis: A morphological
alteration independent of pseudoalcoholic liver disease. Hepatology
1988, 8(5):1063-1068.
- 51. Martin W, Standing J: Amiodarone pulmonary toxicity: biochemical
evidence for a cellular phospholipidosis in the bronchoalveolar lavage
of human subjects. Journal of Pharmacology and Experimental
Therapeutics 1988, 244(2):774-779.
- 52. Hauw J-J, Boutry J-M, Albouz S, Harpin M, Baudrimont M, Escourolle
R, et al: Perhexiline maleate-induced lipidosis in cultured
human fibroblasts: cell kinetics, ultrastructural and biochemical
studies. Virchows Arch B Cell Pathology 1980, 34(1):239-249.
- 53. Yoshimura S, Hayashi Y: Ultrastructural alteratons of peripheral
ganglia in rats by phospholipidosis-inducing drugs (The 5th Meeting
for the Study of Toxic Effect). Journal of Toxicological Sciences
1978, 3(3):249-250.
- 54. Pessayre D, Bichara M, Feldmann M, Degott C, Potet F, Benhamou
JP: Perhexiline maleate-induced cirrhosis. Gastroenterology 1979,
76(1):170-177.
- 55. Felix A, Feuer G, McGuire EJ, Takada A: Morphological and
biochemical changes in the liver of various species in experimental
phospholipidosis after diethylaminoethoxyhexestrol treatment. Toxicology
and Applied Pharmacology 1975, 34(1):28-44.
- 56. Tashiro Y, Watanabe Y, Enomoto Y: Experimental phospholipidosis
induced by 4, 4′‐diethyl‐aminoethoxyhexestrol. Pathology International
1983, 33(5): 929-942.
- 57. Yamamoto A, Adachi S, Ishikawa K, Yokomura T, Kitani T, Terushi
N, et al.: Studies on drug-induced lipidosis. The Journal of Biochemistry
1971, 70(5):775-784.
- 58. Carlier M-B, Rollman B, Van Hoof Fi, Tulkens P: Mechanism of
aminoglycoside-induced lysosomal phospholipidosis: in vitro and in
vivo studies with gentamicin and amikacin. Biochemical Pharmacology
1982, 31(23):3861-3870.
- 59. Josepovitz C, Levine R, Farruggella T, Kaloyanides GJ: Comparative
effects of aminoglycosides on renal cortical and urinary phospholipids
in the rat. Experimental Biology and Medicine 1986, 182(1):1-5.
- 60. Kacew S: Cationic amphiphilic drug-induced renal cortical lysosomal
phospholipidosis: an in vivo comparative study with gentamicin
and chlorphentermine. Toxicology and Applied Pharmacology 1987,
91(3):469-476.
- 61. Giuliano RA, Paulus GJ, Verpooten GA, Pattyn VM, Pollet DE,
Nouwen EJ, et al.: Recovery of cortical phospholipidosis and necrosis
after acute gentamicin loading in rats. Kidney International 1984,
26(6):838-847.
- 62. Feldman S, Wang M, Kaloyanides G: Aminoglycosides induce a
phospholipidosis in the renal cortex of the rat: an early manifestation
of nephrotoxicity. Journal of Pharmacology and Experimental Therapeutics
1982, 220(3):514-520.
- 63. De Broe ME, Paulus GJ, Verpooten GA, Roels F, Buyssens N, Wedeen
R, et al.: Early effects of gentamicin, tobramycin, and amikacin on
the human kidney. Kidney International 1984, 25(4):643-652.
- 64. Van Bambeke F, Gerbaux C, Michot J-M, d'Yvoire MB, Montenez
J-P, Tulkens PM: Lysosomal alterations induced in cultured rat
fibroblasts by long-term exposure to low concentrations of azithromycin.
Journal of Antimicrobial Chemotherapy 1998; 42(6):761-767.
- 65. Liu Y, Kam WR, Ding J, Sullivan DA: One man's poison is another
man's meat: using azithromycin-induced phospholipidosis to promote
ocular surface health. Toxicology 2014, 320:1-5.
- 66. Van Bambeke F, Montenez J-P, Piret J, Tulkens PM, Courtoy PJ,
Mingeot-Leclercq M-P: Interaction of the macrolide azithromycin
with phospholipids. I. Inhibition of lysosomal phospholipase A 1
activity. European Journal of Pharmacology 1996, 314(1-2):203-214.
- 67. Hopkins S: Clinical toleration and safety of azithromycin. The
American Journal of Medicine 1991, 91(3):40-45.
- 68. Gray J, Purmalis A, Purmalis B, Mathews J: Ultrastructural studies of
the hepatic changes brought about by clindamycin and erythromycin
in animals. Toxicology and Applied Pharmacology 1971, 19(2):217-
233.
- 69. Cox JW, Ulrich RG, Larson PG, Cramer CT: Acute hepatocellular
effects of erythromycin, gentamicin, and trospectomycin in the
perfused rat liver: lack of correlation between lamellar body induction
potency and cytotoxicity. Basic & Clinical Pharmacology &
Toxicology 1988, 62(5):337-343.
- 70. Muñoz SJ, Martinez‐Hernandez A, Maddrey WC: Intrahepatic
cholestasis and phospholipidosis associated with the use of trimethoprim‐
sulfamethoxazole. Hepatology 1990, 12(2):342-347.
- 71. Toubeau G, Nonclercq D, Zanen J, Lambricht P, Tulkens PM, Heuson-
Stiennon J-A, et al.: Distribution of epidermal growth factor in
the kidneys of rats exposed to amikacin. Kidney International 1991,
40(4):691-699.
- 72. Cox JW, Ulrich RG, Wynalda MA, Mckenna R, Larsen ER, Ginsberg
LC, et al.: Reversible, hepatic, lysosomal phospholipidosis in rat induced
by subchronic daily administration of trospectomycin sulfate.
Biochemical Pharmacology 1989, 38(20):3535-3541.
- 73. Ulrich RG, Petrella DK, Larsen ER, Cox JW, Cramer CT, Piper
RC, et al.: Hepatic changes produced by 30-day administration of a
novel aminocyclitol antibiotic, trospectomycin sulfate, to laboratory
animals. Fundamental and Applied Toxicology 1990, 14(1):60-70.
- 74. Hansson AL, Xia Z, Berglund MC, Bergstrand A, Depierre JW,
Nässberger L: Reduced cell survival and morphological alterations
induced by three tricyclic antidepressants in human peripheral monocytes
and lymphocytes and in cell lines derived from these cell types.
Toxicology In Vitro 1997, 11(1-2):21-31.
- 75. Lüllmann-Rauch R: Lipidosis-like ultrastructural alterations in rat
lymph nodes after treatment with tricyclic antidepressants or neuroleptics.
Naunyn-Schmiedeberg's Archives of Pharmacology 1974,
286(2):165-179.
- 76. Lüllmann-Rauch R: Lipidosis-like alterations in dorsal root ganglion
cells of rats treated with tricyclic antidepressants. Naunyn-Schmiedeberg's
Archives of Pharmacology. 1974, 283(2):219-222.
- 77. Lüllmann-Rauch R, Scheid D: Intraalveolar foam cells associated
with lipidosis-like alterations in lung and liver of rats treated with
tricyclic psychotropic drugs. Virchows Arch B Cell Pathology 1975,
19:255-268.
- 78. Palmeri S, Mangano L, Battisti C, Malandrini A, Federico A: Imipramine
induced lipidosis and dexamethasone effect: morphological and
biochemical study in normal and chronic GM2 gangliosidosis fibroblasts.
Journal of The Neurological Sciences. 1992, 110(1-2):215-221.
- 79. Xia Z, Ying G, Hansson AL, Karlsson H, Xie Y, Bergstrand A, et al.:
Antidepressant-induced lipidosis with special reference to tricyclic
compounds. Progress in Neurobiology. 2000, 60(6):501-512.
- 80. Drew R, Siddik Z, Mimnaugh E, Gram T: Species and dose differences
in the accumulation of imipramine by mammalian lungs. Drug
Metabolism and Disposition 1981, 9(4):322-326.
- 81. Geist SH, Lüllmann-Rauch R: Experimentally induced lipidosis in
uterine and vaginal epithelium of rats. Annals of Anatomy 1994,
176(1):3-9.
- 82. Bockhardt H, Lüllmann‐Rauch R: Zimelidine‐Induced Lipidosis in
Rats. Basic & Clinical Pharmacology & Toxicology 1980, 47(1):45-
48.
- 83. Kodavanti UP, Lockard VG, Mehendale HM: In vivo toxicity and
pulmonary effects of promazine and chlorpromazine in rats. Journal
of Biochemical and Molecular Toxicology 1990, 5(4):245-251.
- 84. Glaumann H, Bronner U, Ericsson Ö, Gustafsson L, Rombo L: Pentamidine
accumulates in rat liver lysosomes and inhibits phospholipid
degradation. Pharmacology & Toxicology. 1994, 74(1):17-22.
- 85. Filippone E, Carson J, Beckford R, Jaffe B, Newman E, Awsare B, et
al.: Sirolimus-induced pneumonitis complicated by pentamidine-induced
phospholipidosis in a renal transplant recipient: a case report.
Transplantation Proceedings 2011; 43(7):2792-2797.
- 86. Whitehouse L, Menzies A, Mueller R, Pontefract R: Ketoconazole-
induced hepatic phospholipidosis in the mouse and its association
with de-N-acetyl ketoconazole. Toxicology. 1994, 94(1-3):81-95.
- 87. Pakuts A, Parks R, Paul C, Bujaki S, Mueller R: Ketoconazole-induced
hepatic lysosomal phospholipidosis: the effect of concurrent
barbiturate treatment. Research Communications in Chemical
Pathology and Pharmacology 1990, 67(1):55-62.
- 88. Lüllmann H, Lüllmann-Rauch R: Tamoxifen-induced generalized
lipidosis in rats subchronically treated with high doses. Toxicology
and Applied Pharmacology 1981, 61(1):138-146.
- 89. Huang L-K, Tsai M-J, Tsai H-C, Chao H-S, Lin F-C, Chang S-C: Statin-
induced lung injury: diagnostic clue and outcome. Postgraduate
Medical Journal 2013, 89:14-19.
- 90. Lantuejoul S, Brambilla E, Brambilla C, Devouassoux G: Statin-
induced fibrotic nonspecific interstitial pneumonia. European
Respiratory Journal 2002, 19(3):577-580.
- 91. Matsuzawa Y, Hostetler KY: Inhibition of lysosomal phospholipase
A and phospholipase C by chloroquine and 4,4-bis(diethylaminoethoxy)
α,β-diethyldiphenylethane. The Journal of Biological
Chemistry 1980, 255:5190-5194.
- 92. Hallberg A, Naeser P, Andersson A: Effects of long‐term chloroquine
exposure on the phospholipid metabolism in retina and pigment epithelium
of the mouse. Acta Ophthalmologica. 1990, 68(2):125-130.
- 93. Gräbner R, Meerbach W: Imipramine and chloroquine induced alterations
in phospholipid content of rat lung. Experimental Pathology
1983, 24(4):253-259.
- 94. Matsuzawa Y, Hostetler KY: Studies on drug-induced lipidosis:
subcellular localization of phospholipid and cholesterol in the liver
of rats treated with chloroquine or 4, 4'-bis (diethylaminoethoxy)
alpha, beta-diethyldiphenylethane. Journal of Lipid Research 1980,
21(2):202-214.
- 95. Jones C, Salisbury RS, Jayson M: The presence of abnormal lysosomes
in lymphocytes and neutrophils during chloroquine therapy: a
quantitative ultrastructural study. Annals of The Rheumatic Diseases
1984, 43:710-715.
- 96. Mũller-Hõcker J, Schmid H, Weiss M, Dendorfer U, Braun G: Chloroquine-
induced phospholipidosis of the kidney mimicking Fabry's
disease: case report and review of the literature. Human Pathology
2003, 34(3):285-289.
- 97. Bonanomi MT, Dantas NC, Medeiros FA: Retinal nerve fibre layer
thickness measurements in patients using chloroquine. Clinical &
Experimental Ophthalmology 2006, 34(2):130-136.
- 98. Roos JM, Aubry M-C, Edwards WD: Chloroquine cardiotoxicity:
clinicopathologic features in three patients and comparison with
three patients with Fabry disease. Cardiovascular Pathology 2002,
11(5):277-283.
- 99. Brealey J, Carroll R: Hydroxychloroquine-induced phospholipidosis
in a renal transplant patient. Ultrastructural Pathology 2017,
41(1):124-125.
- 100. Costa R: Hydroxychloroquine, Renal phospholipidosis: case report.
Reactions 2013, 1470(1):24.
- 101. Khubchandani SR, Bichle LS: Hydroxychloroquine-induced
Phospholipidosis in a Case of SLE: The Wolf in Zebra Clothing.
Ultrastructural Pathology 2013, 37(2):146-150.
- 102. Heath M, Jacobson W: The inhibition of lysosomal phospholipase A
from rabbit lung by ambroxol and its consequences for pulmonary
surfactant. Lung 1985, 163(1):337-344.
- 103. Von Wichert P, Bavendamm U, Von Teichmann M, Müller G,
Thalheim E, Wilke A, et al.: Increased incorporation of fatty acids
into phospholipids of lungs and livers of rabbits under the influence
of bromhexine and ambroxol. Naunyn-Schmiedeberg's Archives of
Pharmacology 1977, 297(3):269-273.
- 104. Gil J, Thurnheer U: Morphometric evaluation of ultrastructural
changes in type II alveolar cells of rat lung produced by bromhexine.
Respiration 1971, 28(5):438-456.
- 105. Reasor M, Heyneman C, Walker E: Chlorcyclizine--induced
pulmonary phospholipidosis in rats. Research Communications In
Chemical Pathology and Pharmacology 1982; 38(2):235-246.
- 106. Ploemen J-PH, Kelder J, Hafmans T, van de Sandt H, van Burgsteden
JA, Salemink PJ, et al.: Use of physicochemical calculation
of pKa and CLogP to predict phospholipidosis-inducing potential:
a case study with structurally related piperazines. Experimental and
Toxicologic Pathology 2004, 55(5):347-355.
- 107. Pelletier DJ, Gehlhaar D, Tilloy-Ellul A, Johnson TO, Greene N:
Evaluation of a published in silico model and construction of a novel
Bayesian model for predicting phospholipidosis inducing potential.
Journal of Chemical Information and Modeling 2007, 47(3):1196-
1205.
- 108. Hanumegowda UM, Wenke G, Regueiro-Ren A, Yordanova R,
Corradi JP, Adams SP: Phospholipidosis as a function of basicity,
lipophilicity, and volume of distribution of compounds. Chemical
Research In Toxicology 2010, 23(4):749-755.
- 109. Choi SS, Kim JS, Valerio LG, Sadrieh N: In silico modeling to
predict drug-induced phospholipidosis. Toxicology and Applied
Pharmacology 2013, 269(2):195-204.
- 110. Kruhlak NL, Choi SS, Contrera JF, Weaver JL, Willard JM, Hastings
KL, et al.: Development of a phospholipidosis database and predictive
quantitative structure-activity relationship (QSAR) models.
Toxicology Mechanisms and Methods 2008, 18(2-3):217-227.
- 111. Orogo AM, Choi SS, Minnier BL, Kruhlak NL: Construction and
consensus performance of (q)sar models for predicting phospholipidosis
using a dataset of 743 compounds. Molecular Informatics 2012,
31(10):725-739.
- 112. Liu N, Tengstrand EA, Chourb L, Hsieh FY: Di-22: 6-bis (monoacylglycerol)
phosphate: a clinical biomarker of drug-induced phospholipidosis
for drug development and safety assessment. Toxicology
and Applied Pharmacology 2014, 279(3):467-476.
- 113. Chatman LA, Morton D, Johnson TO, Anway SD: A strategy for
risk management of drug-induced phospholipidosis. Toxicologic
Pathology 2009, 37(7):997-1005.
- 114. Park S, Choi YJ, Lee BH: In vitro validation of drug-induced
phospholipidosis. The Journal of Toxicological Sciences 2012,
37(2):261-267.
- 115. Bauch C, Bevan S, Woodhouse H, Dilworth C, Walker P: Predicting
in vivo phospholipidosis-inducing potential of drugs by a combined
high content screening and in silico modelling approach. Toxicology
In Vitro 2015, 29(3):621-630.
- 116. Frederick TE, Chebukati JN, Mair CE, Goff PC, Fanucci GE: Bis
(monoacylglycero) phosphate forms stable small lamellar vesicle
structures: insights into vesicular body formation in endosomes.
Biophysical Journal 2009, 96(5):1847-1855.
- 117. Tengstrand EA, Miwa GT, Hsieh FY: Bis (monoacylglycerol)
phosphate as a non-invasive biomarker to monitor the onset and
time-course of phospholipidosis with drug-induced toxicities. Expert
Opinion on Drug Metabolism & Toxicology 2010, 6(5):555-570.
- 118. Thompson KL, Haskins K, Rosenzweig BA, Stewart S, Zhang J,
Peters D, et al.: Comparison of the diagnostic accuracy of di-22:
6-bis (monoacylglycerol) phosphate and other urinary phospholipids
for drug-induced phospholipidosis or tissue injury in the rat. International
Journal of Toxicology 2012, 31(1):14-24.
- 119. Thompson KL, Zhang J, Stewart S, Rosenzweig BA, Shea K,
Mans D, et al.: Comparison of urinary and serum levels of di-22:
6-bis (monoacylglycerol) phosphate as noninvasive biomarkers of
phospholipidosis in rats. Toxicology Letters 2012, 213(2):285-291.
120. Baronas ET, Lee J-W, Alden C, Hsieh FY: Biomarkers to monitor
drug-induced phospholipidosis. Toxicology and Applied Pharmacology
2007, 218(1):72-78.
- 121. Abe A, Hiraoka M, Shayman JA: A role for lysosomal phospholipase
A2 in drug induced phospholipidosis. Drug Metabolism Letters
2007, 1(1):49-53.
- 122. Ceccarelli M, Germani R, Massari S, Petit C, Nurisso A, Wolfender
J-L, et al.: Phospholipidosis effect of drugs by adsorption into lipid
monolayers. Colloids Surfaces B: Biointerfaces 2015, 136:175-184.
- 123. Yudate HT, Kai T, Aoki M, Minowa Y, Yamada T, Kimura T, et al.:
Identification of a novel set of biomarkers for evaluating phospholipidosis-
inducing potential of compounds using rat liver microarray
data measured 24-h after single dose administration. Toxicology
2012, 295(1-3):1-7.
- 124. Sawada H, Taniguchi K, Takami K: Improved toxicogenomic
screening for drug-induced phospholipidosis using a multiplexed
quantitative gene expression ArrayPlate assay. Toxicology In Vitro
2006, 20(8): 1506-1513.