Toxicologic pathological mechanism of acute lung injury induced by oral administration of benzalkonium chloride in mice
Tóm tắt
Benzalkonium chloride (BAC) intoxication causes fatal lung injuries, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the pathogenesis of ALI/ARDS induced by BAC ingestion is poorly understood. This study aimed to clarify the mechanism of lung toxicity after BAC ingestion in a mouse model. BAC was orally administered to C57BL/6 mice at doses of 100, 250, and 1250 mg/kg. After administration, BAC concentrations in the blood and lungs were evaluated via liquid chromatography with tandem mass spectrometry. Lung tissue injury was evaluated via histological and protein analyses. Blood and lung BAC concentration levels after oral administration increased in a dose-dependent manner, with the concentrations directly proportional to the dose administered. The severity of lung injury worsened over time after the oral administration of 1250 mg/kg BAC. An increase in the terminal transferase dUTP nick end labeling-positive cells and cleaved caspase-3 levels was observed in the lungs after 1250 mg/kg BAC administration. In addition, increased cleaved caspase-9 levels and mitochondrial cytochrome c release into the cytosol were observed. These results suggest that lung tissue injury with excessive apoptosis contributes to BAC-induced ALI development and exacerbation. Our findings provide useful information for developing an effective treatment for ALI/ARDS induced by BAC ingestion.
Tài liệu tham khảo
Jono K, Takayama T, Kuno M, Higashide E (1986) Effect of alkyl chain length of benzalkonium chloride on the bactericidal activity and binding to organic materials. Chem Pharm Bull (Tokyo) 34:4215–4224. https://doi.org/10.1248/cpb.34.4215
Hitosugi M, Maruyama K, Takatsu A (1998) A case of fatal benzalkonium chloride poisoning. Int J Legal Med 111:265–266. https://doi.org/10.1007/s004140050166
Külbay H, Çevik ŞE, Vural Z (2014) A case of accidental benzalkonium chloride (10%) ingestion. Turk J Fam Med Prim Care 8:129–132. https://doi.org/10.5455/tjfmpc.165553
Spiller HA (2014) A case of fatal ingestion of a 10% benzalkonium chloride solution. J Forensic Toxicol Pharmacol. https://doi.org/10.4172/2325-9841.1000113
Mishima-Kimura S, Yonemitsu K, Ohtsu Y, Sasao A, Tsutsumi H, Furukawa S, Nishitani Y (2018) Liquid chromatography-tandem mass spectrometry detection of benzalkonium chloride (BZK) in a forensic autopsy case with survival for 18 days post BZK ingestion. Leg Med (Tokyo) 32:48–51. https://doi.org/10.1016/j.legalmed.2018.02.006
Kumar A, Chetiwal R, Rastogi P, Tanwar S, Gupta S, Patnaik R, Vankayalapati M, Gupta S, Arya A (2021) Severe esophagitis and chemical pneumonitis as a consequence of dilute benzalkonium chloride ingestion: a case report. Int J Med Stud 9:231–234. https://doi.org/10.5195/ijms.2021.969
Handrean IGE, Bagiada IM, Andrika P, Sajinadiyasa IGK (2021) Acute respiratory distress syndrome (ARDS) caused by benzalkonium chloride (BAC) 15% intoxication. Int J Med Rev Case Rep 5:28–32. https://doi.org/10.5455/IJMRCR.ards-Benzalkonium-Chloride
Miyauchi M, Hayashida M, Yokota H (2014) Benzalkonium chloride intoxication caused by intravenous self-injection. Chudoku Kenkyu 27:327–332. http://jsct-web.umin.jp/
Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353:1685–1693. https://doi.org/10.1056/NEJMoa050333
Matthay MA, Ware LB, Zimmerman GA (2012) The acute respiratory distress syndrome. J Clin Invest 122:2731–2740. https://doi.org/10.1172/JCI60331
Umbrello M, Formenti P, Bolgiaghi L, Chiumello D (2016) Current concepts of ARDS: a narrative review. Int J Mol Sci 18:64. https://doi.org/10.3390/ijms18010064
Thille AW, Esteban A, Fernández-Segoviano P, Rodriguez JM, Aramburu JA, Vargas-Errázuriz P, Martín-Pellicer A, Lorente JA, Frutos-Vivar F (2013) Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies. Lancet Respir Med 1:395–401. https://doi.org/10.1016/S2213-2600(13)70053-5
Castro CY (2006) ARDS and diffuse alveolar damage: a pathologist’s perspective. Semin Thorac Cardiovasc Surg 18:13–19. https://doi.org/10.1053/j.semtcvs.2006.02.001
Deutschle T, Porkert U, Reiter R, Keck T, Riechelmann H (2006) In vitro genotoxicity and cytotoxicity of benzalkonium chloride. Toxicol In Vitro 20:1472–1477. https://doi.org/10.1016/j.tiv.2006.07.006
Pauly A, Meloni M, Brignole-Baudouin F, Warnet JM, Baudouin C (2009) Multiple endpoint analysis of the 3D-reconstituted corneal epithelium after treatment with benzalkonium chloride: early detection of toxic damage. Invest Ophthalmol Vis Sci 50:1644–1652. https://doi.org/10.1167/iovs.08-2992
Kim SH, Kwon D, Lee S, Son SW, Kwon JT, Kim PJ, Lee YH, Jung YS (2020) Concentration- and time-dependent effects of benzalkonium chloride in human lung epithelial cells: necrosis, apoptosis, or epithelial mesenchymal transition. Toxics 8:17. https://doi.org/10.3390/toxics8010017
Vitoux MA, Kessal K, Melik Parsadaniantz S, Claret M, Guerin C, Baudouin C, Brignole-Baudouin F, Réaux-Le Goazigo A (2020) Benzalkonium chloride-induced direct and indirect toxicity on corneal epithelial and trigeminal neuronal cells: proinflammatory and apoptotic responses in vitro. Toxicol Lett 319:74–84. https://doi.org/10.1016/j.toxlet.2019.10.014
Kanno S, Hirano S, Kato H, Fukuta M, Mukai T, Aoki Y (2020) Benzalkonium chloride and cetylpyridinium chloride induce apoptosis in human lung epithelial cells and alter surface activity of pulmonary surfactant monolayers. Chem Biol Interact 317:108962. https://doi.org/10.1016/j.cbi.2020.108962
Kawasaki M, Kuwano K, Hagimoto N, Matsuba T, Kunitake R, Tanaka T, Maeyama T, Hara N (2000) Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. Am J Pathol 157:597–603. https://doi.org/10.1016/S0002-9440(10)64570-1
Xue Y, Hieda Y, Kimura K, Nishiyama T, Adachi T (2002) Sensitive determination of benzalkonium chloride in blood and tissues using high-performance liquid chromatography with solid-phase extraction. Leg Med (Tokyo) 4:232–238. https://doi.org/10.1016/s1344-6223(02)00036-6
Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, Kuebler WM, Acute Lung Injury in Animals Study Group (2011) An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol 44:725–738. https://doi.org/10.1165/rcmb.2009-0210ST
Sekijima H, Hiramoto K, Kozawa S (2020) A decrease in the tear secretion volume in a mouse model with ulcerative colitis. Cutan Ocul Toxicol 39:363–369. https://doi.org/10.1080/15569527.2020.1825471
Cosmet Ingredient Rev Expert Panel Staff USA (1989) 2 Final report on the safety assessment of benzalkonium chloride. J Am Coll Toxicol 8:589–625. https://doi.org/10.3109/10915818909010524
Xue Y, Zhang S, Tang M, Zhang T, Wang Y, Hieda Y, Takeshita H (2012) Comparative study on toxic effects induced by oral or intravascular administration of commonly used disinfectants and surfactants in rats. J Appl Toxicol 32:480–487. https://doi.org/10.1002/jat.1662
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337
Shi Y (2001) A structural view of mitochondria-mediated apoptosis. Nat Struct Biol 8:394–401. https://doi.org/10.1038/87548
Goldstein MH, Silva FQ, Blender N, Tran T, Vantipalli S (2022) Ocular benzalkonium chloride exposure: problems and solutions. Eye (Lond) 36:361–368. https://doi.org/10.1038/s41433-021-01668-x
Cai J, Yang J, Jones DP (1998) Mitochondrial control of apoptosis: the role of cytochrome c. Biochim Biophys Acta 1366:139–149. https://doi.org/10.1016/s0005-2728(98)00109-1
Kulms D, Schwarz T (2000) Molecular mechanisms of UV-induced apoptosis. Photodermatol Photoimmunol Photomed 16:195–201. https://doi.org/10.1034/j.1600-0781.2000.160501.x
Perini GF, Ribeiro GN, Pinto Neto JV, Campos LT, Hamerschlak N (2018) BCL-2 as therapeutic target for hematological malignancies. J Hematol Oncol 11:65. https://doi.org/10.1186/s13045-018-0608-2
Datta S, He G, Tomilov A, Sahdeo S, Denison MS, Cortopassi G (2017) In vitro evaluation of mitochondrial function and estrogen signaling in cell lines exposed to the antiseptic cetylpyridinium chloride. Environ Health Perspect 125:087015. https://doi.org/10.1289/EHP1404
Debbasch C, Brignole F, Pisella PJ, Warnet JM, Rat P, Baudouin C (2001) Quaternary ammoniums and other preservatives’ contribution in oxidative stress and apoptosis on Chang conjunctival cells. Invest Ophthalmol Vis Sci 42:642–652. https://iovs.arvojournals.org/
Okamoto A, Tanaka M, Sumi C, Oku K, Kusunoki M, Nishi K, Matsuo Y, Takenaga K, Shingu K, Hirota K (2016) The antioxidant N-acetyl cysteine suppresses lidocaine-induced intracellular reactive oxygen species production and cell death in neuronal SH-SY5Y cells. BMC Anesthesiol 16:104. https://doi.org/10.1186/s12871-016-0273-3
Lee H, Park K (2019) Acute toxicity of benzalkonium chloride in BALB/c mice following intratracheal instillation and oral administration. Environ Anal Health Toxicol 34:e2019009. https://doi.org/10.5620/eaht.e2019009
De Saint Jean M, Brignole F, Bringuier AF, Bauchet A, Feldmann G, Baudouin C (1999) Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci 40:619–630. https://iovs.arvojournals.org/
Mannou H, Ikemura M, Nagakawa Y, Nata M, Inoue H (2014) An autopsy case of serotonin toxicity resulting from suicidal administrations of fluvoxamine and lithium. Rom J Leg Med 22:59–62. https://doi.org/10.4323/rjlm.2014.59
Oshima T, Sasao A, Sekijima H, Kotani H (2023) A case of carbon monoxide poisoning before a vehicle fire: availability of volatile hydrocarbons analysis. Leg Med (Tokyo) 60:102174. https://doi.org/10.1016/j.legalmed.2022.102174