Objective To construct a model of acute ethylene glycol poisoning in SD rats by gavage and compare the brain, heart and kidney injury, so as to provide more reference for related animal experiments and early clinical identification and intervention.
Methods Thirty SPF male SD rats were divided into 3 groups by random number table method, 10 rats in blank control group (NC group): gavage normal saline at 12 mL·kg-1; 10 rats in low dose ethylene glycol gavage group (EG-L group) and 10 rats in high dose ethylene glycol gavage group (EG-H group) were gavage 60% and 80% ethylene glycol solution at 12 mL·kg-1. The survival and death of rats in each group were observed within 48 h; and 48 h after modeling, blood sampling from abdominal aorta was performed, and rats were sacrificed to collect brain, heart, kidney and other related organs. The pathological changes of brain, heart and kidney tissues were observed by HE staining, and the calcium oxalate crystals in brain and kidney tissues were observed by Pizzolatto staining. The behavioral changes were determined by the balance ability score. The heart rate and urine volume changes were observed by wearable electrocardiograph sensor and urine volume monitoring. The levels of S100 calcium-binding protein β (S100-β), troponin I (cTnI) and kidney injury molecule-1 (KIM-1) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The levels of oxalate in blood of rats in each group were detected by visible light spectrophotometry.
Results The 48 h cumulative survival rates of NC group, EG-L group and EG-H group were 100%, 90% and 70%, respectively. Compared with NC group, the pathological changes of brain and kidney tissues in EG gavage groups were obvious, and obvious calcium oxalate crystal deposition in brain vessels and renal tubules of rats were observed (all P﹤0.05), and the deposition in brain vessels and renal tubules of rats in EG-H group was more obvious (P﹤0.05). The balance ability of the two groups of rats after gavage of EG was lower than that of the NC group (P﹤0.05), and the decrease was more obvious in the EG-H group (P﹤0.05). Compared with the NC group, the heart rate of the rats in the EG-L and EG-H groups was increased at 12 h, 18 h, 24 h, 30 h after gavage (all P﹤0.05), and the urine volume was decreased at 30~36 h, 36~42 h, 42~48 h (all P﹤0.05), and the urine volume of the EG-H group was more obvious at 36~42 h, 42~48 h (P﹤0.05). Compared with the NC group, the serum levels of S100-β and KIM-1 in the EG-L and EG-H groups were increased (all P﹤0.05), and the serum levels of S100-β and KIM-1 in the EG-H group were higher than those in the EG-L group (all P﹤0.05). The oxalate content in the two groups of rats after gavage of EG was increased compared with the NC group (all P﹤0.05), and the oxalate content in the EG-H group was higher (P﹤0.05).
Conclusion The rat model of acute ethylene glycol poisoning can be better constructed by gavage of 80% ethylene glycol solution at a dose of 12mL·kg-1. Acute ethylene glycol poisoning can cause multiple organ damage in rats, and the manifestations of poisoning occur and develop in a time-phrased manner.
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1.Kruse JA. Methanol and ethylene glycol intoxication[J]. Crit Care Clin, 2012, 28(4): 661-711 .DOI: 10.1016/j.ccc. 2012.07.002.
2.Ross JA, Borek HA, Holstege CP, et al. Toxic Alcohol poisoning[J]. Emerg Med Clin North Am, 2022, 40(2): 327-341. DOI: 10.1016/j.emc.2022.01.012.
3.Porter WH. Ethylene glycol poisoning: quintessential clinical toxicology; analytical conundrum[J]. Clinica Chimica Acta, 2011, 413(3-4): 365-377. DOI: 10.1016/j.cca.2011.10.034.
4.Ahmad Y, Kissling S, Torrent C, et al. The three biological gaps and hyperoxaluria in ethylene glycol poisoning: case presentation and review[J]. Eur Rev Med Pharmacol Sci, 2021, 25(20): 6295-6299. DOI: 10.26355/eurrev_202110_26999.
5.Sidlak AM, Marino RT, Van Meerbeke JP, et al. Single versus continued dosing of fomepizole during hemodialysis in ethylene glycol toxicity[J]. Clin Toxicol(Phila), 2021, 59(2): 106-110. DOI: 10.1080/15563650.2020.1770780.
6.Bervinova AV, Borozdina NA, Palikov VA, et al. Discerning comparison of 1 and 0.5% ethylene glycol in sprague-dawley rats with modeled urolithiasis[J]. Bull Exp Biol Med, 2022, 173(5): 673-676. DOI: 10.1007/s10517-022-05611-2.
7.Azimi A, Eidi A, Mortazavi P, et al. Protective effect of apigenin on ethylene glycol-induced urolithiasis via attenuating oxidative stress and inflammatory parameters in adult male Wistar rats[J]. Life Sci, 2021, 279: 119641. DOI: 10.1016/j.lfs.2021.119641.
8.Roberts DM, Hoffman RS, Brent J, et al. The serum glycolate concentration: its prognostic value and its correlation to surrogate markers in ethylene glycol exposures[J]. Clin Toxicol (Phila), 2022, 60(7): 798-807. DOI: 10.1080/15563650.2022.2049811.
9.Fowles J, Banton M, Klapacz J, et al. A toxicological review of the ethylene glycol series: commonalities and differences in toxicity and modes of action[J]. Toxicol Lett, 2017, 278: 66-83. DOI: 10.1016/j.toxlet.2017.06.009.
10.Catlin NR, Bowman CJ, Engel SM, et al. Reproductive and developmental toxicity assessment of palbociclib, a CDK4/6 inhibitor, in Sprague-Dawley rats and New Zealand White rabbits[J]. Reprod Toxicol, 2019, 88: 76-84. DOI: 10.1016/j.reprotox.2019.07.016.
11.Patel R, Mistry AM, Mistry CM. Unintentional ethylene glycol poisoning in an adolescent[J]. Cureus, 2020, 12(11): e11521. DOI: 10.7759/cureus.11521.
12.Wang C, Hiremath S, Sikora L, et al. Kidney outcomes after methanol and ethylene glycol poisoning: a systematic review and Meta-analysis[J]. Clin Toxicol (Phila), 2023, 61(5): 326-335. DOI: 10.1080/15563650.2023.2200547.
13.Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management[J]. Clin J Am Soc Nephrol, 2008, 3(1): 208-225. DOI: 10.2215/CJN.03220807.
14.Latus J, Kimmel M, Alscher MD, et al. Ethylene glycol poisoning: a rare but life-threatening cause of metabolic acidosis-a single-centre experience[J]. Clin Kidney J, 2012, 5(2): 120-123. DOI: 10.1093/ckj/sfs009.
15.Ahmed A, Tschetter PA, Krasowski MD, et al. Massive ethylene glycol poisoning triggers osmotic demyelination syndrome[J]. J Emerg Med, 2014, 46(3): e69-74. DOI: 10.1016/j.jemermed.2013.08.068.
16.Thanacoody RH, Gilfillan C, Bradberry SM, et al. Management of poisoning with ethylene glycol and methanol in the UK: a prospective study conducted by the National Poisons Information Service[J]. Clin Toxicol(Phila), 2016, 54(2): 134-140. DOI: 10.3109/15563650.2015.1116044.
17.Tuero G, González J, Sahuquillo L, et al. Value of glycolic acid analysis in ethylene glycol poisoning: A clinical case report and systematic review of the literature[J]. Forensic Sci Int, 2018, 290: e9-e14. DOI: 10.1016/j.forsciint.2018.07.007.
18.Stašinskis R, Stašinska K, Mukāns M, et al. Changes in ionized calcium in ethylene glycol poisoning[J]. Proc (Bayl Univ Med Cent), 2022, 35(4): 460-465. DOI: 10.1080/08998280.2022.2062550.
19.王秋实, 李晓冉,姚瑶. 沙库巴曲缬沙坦片对慢性心功能不全患者血浆NT-proBNP、cTnI表达及心功能的影响[J]. 中国药师, 2023, 26(11): 298-303. [Wang QS, Li XR, Yao Y. The effects of sacubitril-valsartan tablets on the expressions of NT-proBNP, cTnI and cardiac function in patients with chronic cardiac insufficiency[J]. China Pharmacist, 2023, 26(11): 298-303.] DOI: 10.12173/j.issn.1008-049X.202311096.
20.Huo W, Zhang K, Nie Z, et al. Kidney injury molecule-1 (KIM-1): a novel kidney-specific injury molecule playing potential double-edged functions in kidney injury[J]. Transplant Rev (Orlando), 2010, 24(3): 143-146. DOI: 10.1016/j.trre.2010.02.002.
21.Alserr AH, Elwan H, Antonopoulos CN, et al. Using serum s100-β protein as a biomarker for comparing silent brain injury in carotid endarterectomy and carotid artery stenting[J]. Int Angiol, 2019, 38(2): 136-142.DOI: 10.23736/S0392-9590.19.04079-3.